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The Journal of Neuroscience, July 15, 1999, 19(14):6037-6057
Development of Topography within Song Control Circuitry of Zebra
Finches during the Sensitive Period for Song Learning
Soumya
Iyengar,
Sandya S.
Viswanathan, and
Sarah W.
Bottjer
Department of Biology, University of Southern California, Los
Angeles, California 90089-2520
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ABSTRACT |
Refinement of topographic maps during sensitive periods of
development is a characteristic feature of diverse sensory and motor
circuits in the nervous system. Within the neural system that controls
vocal learning and behavior in zebra finches, axonal connections of the
cortical nucleus lMAN demonstrate striking functional and morphological
changes during vocal development in juvenile males. These circuits are
uniquely important for song production during the sensitive period for
vocal learning, and the overall size of these brain regions and their
patterns of axonal connectivity undergo dramatic growth and regression
during this time. Axonal connections to and from lMAN are
topographically organized in adult males that have already learned
song. We wondered whether the large-scale changes seen in lMAN
circuitry during the time that vocal behavior is being learned and
refined could be accompanied by the emergence of topographic mapping.
However, results presented herein demonstrate that most of these
song-control circuits show the same broad patterns of axonal
connectivity between subregions of individual nuclei at the onset of
song learning as seen in adult birds. Thus, coarse topographic
organization is not dependent on the types of experience that are
crucial for vocal learning. Furthermore, this maintenance of
topographic organization throughout the period of song learning is
clearly not achieved by maintenance of static axonal arbors. In fact,
because the volumes of song-control nuclei are growing (or regressing),
topography must be maintained by active remodeling of axonal arbors to
adapt to the changes in overall size of postsynaptic targets. A salient exception to this pattern of conserved topography is the projection from lMAN to the motor cortical region RA: this pathway is diffusely organized at the onset of song learning but undergoes substantial refinement during early stages of song learning, suggesting that remodeling of axonal connections within this projection during the
period of vocal learning may signify the production of increasingly refined vocal utterances.
Key words:
topography; sensitive periods; zebra finch; songbird; vocal learning; axon arbors; basal ganglia
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INTRODUCTION |
Two fundamental questions of
developmental neurobiology pertain to how the brain gets wired up
correctly and how the specificity of neural connections relates to the
emergence of learned behaviors during sensitive periods of development.
Whereas some neural circuits demonstrate remarkably precise patterns of
connectivity very early in postnatal development (for example, the
somatosensory system in rats) (Catalano et al., 1991 ; Agmon et al.,
1993, 1995), other circuits lack topographic specificity in young
animals and are sculpted during specific sensitive periods of
development to give rise to topographically organized circuits in
adults (such as the retinocollicular system in rats) (O'Leary et al.,
1986; Simon and O'Leary, 1992). Thus, different developmental
mechanisms underlie the emergence of topographic organization within
different neural circuits.
The neural substrate that controls vocal behavior in songbirds has
provided a model system for studying the development of neural
circuitry involved in learning a complex behavior. Neural pathways that
control vocal behavior in male zebra finches show striking functional
and morphological changes during vocal development. One developmentally
regulated vocal-control circuit consists of a striatothalamocortical
pathway: Area X (within avian striatum) projects to the thalamic
nucleus medial dorsolateral nucleus of the thalamus (DLM); DLM projects
to the cortical nucleus, lateral magnocellular nucleus of the anterior
neostriatum (lMAN), which projects to the motor cortical regions robust
nucleus of the archistriatum (RA) and dorsal archistriatum (Ad)
(Bottjer et al., 1989; Johnson et al., 1995) (Fig.
1). Lesions within this pathway disrupt
song learning in juvenile birds (20-55 d) but do not affect already learned song in adults ( 90 d) (Bottjer et al., 1984; Sohrabji et al.,
1990; Scharff and Nottebohm, 1991). During the sensitive period for
song learning, the thalamocortical projection from DLM to lMAN
undergoes substantive growth, followed by an equally dramatic
regression between 35 d and adulthood (Johnson and Bottjer, 1992;
cf. Bottjer, 1997; Bottjer and Arnold, 1997; Nordeen and Nordeen,
1997). Because the total number of DLM neurons remains constant
throughout vocal learning, changes in the terminal field of DLM neurons
within lMAN presumably occur at the level of individual DLM axon arbors
(Iyengar and Bottjer, 1998). Synaptic rearrangements must also occur
within the projection from lMAN to RA, because the number of synapses
made by lMAN axons within RA decreases substantially over the course of
vocal learning, whereas the absolute number of lMAN projection neurons
remains constant during this period (Herrmann and Arnold, 1991; Nordeen
et al., 1992).
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Figure 1.
Schematic sagittal view of the song control system
of an adult male zebra finch. Area X (a nucleus of the avian basal
ganglia) projects to the thalamic nucleus DLM. The dorsolateral
(DL) subregion of DLM projects to a central core of
magnocellular neurons within the cortical nucleus lMAN, whereas the
ventromedial (VM) part of DLM projects solely to
a shell surrounding lMANcore, which consists
primarily of parvicellular neurons (Johnson and Bottjer, 1992).
In addition to receiving different afferents, the core and shell
subregions of lMAN project to different targets: whereas
lMANcore projects to RA and Area X,
lMANshell projects to a region adjacent to RA called
Ad (Bottjer et al., 1989; Johnson et al., 1995; Vates and Nottebohm,
1995). X, Area X of the avian striatum;
DLM, medial portion of the dorsolateral region of the
anterior thalamus; lMAN, lateral magnocellular nucleus
of the anterior neostriatum; RA, robust nucleus of the
archistriatum; Ad, dorsal archistriatum;
nXIIts, tracheosyringeal part of the hypoglossal
nucleus; nAm, nucleus ambiguus;
nRAm, nucleus retroambigualis; c, core;
s, shell.
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The DLM lMANRA/Ad pathway actually consists of two
independent circuits that traverse the forebrain in parallel (Johnson et al., 1995) (Fig. 1). Projections within both of these pathways are
topographically organized in adult birds. However, the enormous morphological changes taking place in the volume of individual song-control brain regions and their overall axonal projections suggest that dynamic rearrangements of topographic patterns within song control circuitry may occur during vocal learning (Bottjer, 1997).
We tested this idea by comparing broad patterns of axonal connectivity
within the DLMlMANRA/Ad circuits of male zebra finches during
early stages of song learning with those of adults. Our findings reveal
that the coarse topographic organization of most axonal projections to
and from lMAN is indistinguishable in juvenile and adult birds, despite
the striking growth and regression seen in these brain nuclei during
song learning. These results suggest that broad patterns of topography
within these circuits are already established by the onset of song
learning and do not depend on experiences associated with vocal
learning. Furthermore, these topographic patterns must be maintained in
the face of large-scale changes in song-control circuits by active
remodeling of axonal arbors. A major exception was the
lMANcoreRA circuit in 20 d birds, in which overall
patterns of connectivity were poorly refined as compared with those in
older birds. Interestingly, the adult pattern emerged within this
circuit between 20 and 35 d of age, suggesting that refinement of
topography within this circuit may accompany learning about the
acoustic features of song or their motor representation (Marler, 1991;
Zann, 1996).
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MATERIALS AND METHODS |
All birds used in this study were bred in our aviaries and
received normal exposure to song before surgeries. The surgical procedures used in this study were in accordance with National Institutes of Health guidelines and the Animal Care and Use Committee at the University of Southern California.
Dye injections. Juvenile male zebra finches (18-20 d
after hatching, n = 14; 33-37 d after hatching,
n = 9) and adult male zebra finches (90 d,
n = 18) (Table 1) were
anesthetized with 0.04-0.06 ml of the barbiturate anesthetic
Equithesin and placed in a stereotaxic apparatus. A midline incision
was made in the scalp, and small parts of the skull over lMAN were
removed on both sides of the brain using predetermined coordinates.
Micropipettes (25-30 µm, outer diameter) were filled with the
fluorescent tracers rhodamine dextran amine (RDA) (10% solution in
0.02 M PBS) or fluorescein dextran amine (FDA) (20%
solution in 0.02 M PBS) (Molecular Probes, Eugene, OR) and
lowered into the brain. A Picospritzer was used to make small
injections of different dyes into lMANcore and
lMANshell on both sides of the brain.
For each dye injection, two 10 msec air pulses were made at 35 psi,
yielding a volume of ~2-5 nl at the injection site. Clogging of the
pipette tips led to variations in the size of injections in lMAN within
different birds. Dye injections targeted to both core and shell regions
of lMAN in individual birds were counterbalanced such that if RDA and
FDA were injected into lMANcore and
lMANshell, respectively, on one side of the brain,
then FDA was injected into lMANcore and RDA into
lMANshell on the other side. In addition, some birds
(18-20 d birds, n = 5; 33-37 d birds,
n = 1; adult birds, n = 9) received
injections of RDA alone into right and left lMANcore. After
surgery, juvenile zebra finches were returned to their parents in group
breeding aviaries, whereas adult birds were placed in separate cages. A
survival time of 3 d after surgery was allowed for axonal
transport of the dyes, after which birds were deeply anesthetized and
perfused transcardially with 0.7% saline followed by 10% buffered
formalin. Brains were removed and post-fixed in 10% buffered formalin
for 5-7 d and then cryoprotected in 25% sucrose overnight. A cryostat
( 21°C) was used to section brains coronally at a thickness of 50 µm, and two alternate series of sections were collected on slides
coated with gelatin. One series was coverslipped with buffered glycerol
immediately after sectioning and stored at 4°C. The second series was
allowed to dry overnight, Nissl stained with thionin, and coverslipped
with Permount.
Analysis. In all birds, the first series of slides was
observed under an epifluorescence microscope using rhodamine filters for RDA and fluorescein filters for FDA. Injection sites within lMAN
core and shell and the resulting retrograde and anterograde label in
different regions of the brain were photographed. Retrograde and
anterograde label resulting from dye injections that included parts of
both core and shell regions of lMAN were comparable to patterns of
label produced by injections that included only lMANcore or
lMANshell. Therefore, these injections were included
with injections that were restricted to only lMANcore or
lMANshell for analysis. The thionin-stained series
was used to trace the Nissl-defined borders of lMAN using a camera
lucida. To confirm the exact size and position of the injection sites
within lMAN, injection sites were viewed in the fluorescent series of
slides and traced onto these Nissl-defined outlines. In the same
manner, the Nissl-defined borders of DLM were traced using a camera
lucida, and retrogradely labeled neurons in DLM produced by injections
of RDA and FDA into ipsilateral lMAN were then traced onto these
outlines to determine whether the distribution of labeled cells was
different in juveniles compared with adult birds.
Although both RDA and FDA injections within lMAN produced retrograde
label of comparable brightness, only RDA produced intense anterograde
labeling of axons and terminal arborizations. Anterograde fluorescent
label produced by injections of FDA into lMAN was very weak and
difficult to photograph. Therefore, only patterns of anterograde label
produced by RDA injections into lMAN core and shell were photographed
and compared across birds of different ages.
Qualitative inspection of anterograde label was sufficient for making
comparisons among brains of different ages for all circuits except the
lMANcoreRA projection. Surprisingly, initial inspection of the lMANcoreRA pathway revealed robust age
differences, whereas the organization of the collateral projection from
lMANcore neurons onto Area X appeared to be comparable at
different ages. We decided to confirm these observations by quantifying
the volume of anterogradely labeled arbors within both RA and Area X
produced by injections of RDA into lMANcore. We outlined
the anterograde label within RA and Area X of birds in which both the
injection site in lMANcore and the anterogradely labeled
terminal field in RA and Area X were well defined [20 d
(n = 13), 35 d (n = 5), and adult
(n = 9) birds for RA, Table
2, and 20 d (n = 10)
and adult birds (n = 8) for Area X, Table
3]. An image analysis system was used for capturing images of RA and Area X from both fluorescent and Nissl-stained sections. The area of anterograde label within both these
nuclei was outlined on each section in which they appeared using
software from Media Cybernetics (Image Pro Plus). The total volume of
anterograde label within RA and Area X was estimated by adding these
areas and multiplying by the sampling interval (100 µm). The same
method was used to reconstruct the volume of the RDA injection site in
fluorescent sections of ipsilateral lMANcore. The total
volume of RA and Area X was reconstructed from Nissl-stained sections
(comparison of the cross-sectional area of these nuclei in
Nissl-stained and fluorescent sections showed that these areas were
comparable, i.e., there was no differential shrinkage of the tissue).
Therefore, the borders of RA and Area X were outlined in Nissl-stained
sections, and the resultant areas were added and multiplied by the
sampling interval to estimate the total volume of these nuclei. The
percentage of each nucleus occupied by anterogradely labeled axons from
lMANcore was then calculated by dividing the volume of
labeled axonal arbors within each nucleus in each bird by the total
volume of the respective nucleus (RA or Area X) in that bird (Tables 2,
3).
Despite using a fixed volume of RDA for our injections, the volume of
injection sites in lMAN was variable in different birds, although the
average size of injection sites was roughly comparable between age
groups (Tables 2, 3). There was not a systematic relationship between
the size of the injection and the size of the terminal field within RA
(or Area X), as is typical of any tract tracing study. The absence of a
tight correspondence between the size of the injection site and the
resultant volume of label is caused by several factors. For example,
although one can quantify the volume of the injection site, there is no
way of knowing precisely how much dye is contained within the injection
site or how much dye actually gets incorporated and anterogradely
transported by lMAN neurons. Furthermore, the volume of the terminal
field in each nucleus includes variations in intensity of anterograde
label. Because we wished to quantify the total proportion of RA and
Area X that received input from lMAN neurons, we included all levels of
anterograde label in our quantitative assessment, and this source of
variability also contributes to the lack of a systematic relationship
between the volume of the injection site and that of the terminal
field. Another important consideration is whether the density of
neurons at the injection site remains constant across different ages,
such that injections of similar volume would encompass comparable
numbers of lMANcore neurons at all ages. Although the
absolute number of lMANcore projection neurons remains
constant throughout song learning, an increased density of
lMANcore neurons in adult birds has been reported by some
studies (Nordeen and Nordeen, 1988a,b; Bottjer and Sengelaub,
1989; Nordeen et al., 1992; Nixdorf-Bergweiler et al., 1995; cf.
Bottjer et al., 1985; Burek et al., 1991). Thus, injections of similar
volume would tend to label a slightly larger number of
lMANcore neurons in adult birds compared with juveniles.
However, this tendency would work against the result we describe below,
namely that injections into lMANcore of older animals
actually produce more restricted patterns of anterograde label in RA.
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RESULTS |
Injections into lMANcore of all birds produced
ipsilateral retrograde label in an oval region corresponding to the
dorsolateral part of DLM (DLMDL) and anterograde
label within ipsilateral RA and Area X. Injections into
lMANshell produced ipsilateral retrograde label in a
crescent-shaped region corresponding to ventromedial DLM
(DLMVM), and anterograde label in ipsilateral Ad,
parolfactory lobe (LPO, the medial component of the avian striatum),
and dorsal aspect of caudolateral neostriatum (dNCL, a cortical region
dorsal and lateral to RA and Ad) in all groups of birds studied (Figs. 2-11).
Because of limitations of space, we have not included descriptions of
anterograde label over ipsilateral ventral archistriatum (Av) from RDA
injections into lMAN core and shell as well as retrograde label over
ipsilateral and contralateral Av from injections into lMANshell, which was present in all birds (Johnson
et al., 1995). Control injections of either tracer placed outside the
boundaries of Nissl-defined lMAN did not produce retrograde label in
DLM or anterograde label in RA, Ad, or Area X at any of the ages
studied. However, injections of RDA that were made lateral to the
lateral border of lMANshell produced anterograde label in
the lateral part of LPO and dNCL in an adult and a 35 d bird (data
not shown). Because injections of different fluorescent tracers into
lMANshell and the region lateral to lMANshell
were not made at any age, we could not ascertain whether these regions
have overlapping terminal fields within LPO and dNCL.
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Figure 2.
Photomicrographs of retrograde label within DLM
produced by injections of RDA into different subregions of
lMANcore showing comparable patterns of topography within
the DLMDLlMANcore circuit in birds of
different ages. Injection sites in lMAN (black) are
shown in coronal schematics in the left column, and
dashed outlines depict Nissl-defined borders of DLM in
each photomicrograph on the right. Inset
(below the lMAN schematics) demonstrates the oval dorsolateral
subregion of DLM (DLMDL) and the crescent-shaped
ventromedial part (DLMVM). A,
Retrograde label in the ventral and intermediate parts of
DLMDL resulting from an injection into ventral intermediate
and lateral lMANcore in an adult bird. B, An
injection of RDA into dorsolateral lMANcore produced
retrograde label specifically within the ventral intermediate part of
DLMDL in a 35 d bird. C, RDA-labeled
neurons localized to ventrolateral DLMDL from an injection
into dorsolateral lMANcore in a 20 d bird. Retrograde
label did not extend into the ventromedial subregion of DLM or into
more dorsal subregions of DLMDL in any of these birds.
Scale bar, 200 µm.
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Figure 3.
Camera lucida tracings of coronal sections of DLM
demonstrating the dorsoventral pattern of connectivity within the
DLMDLlMANcore circuit in a 35 d bird.
This bird received injections of RDA in the dorsomedial part
(black injection site) and FDA in the dorsolateral part
(white injection site) of lMANcore,
which are depicted in the schematic at top (above DLM
sections). The resulting pattern of retrograde label in serial coronal
sections of DLM indicated that RDA retrogradely labeled neurons within
dorsal DLMDL (black circles), whereas FDA
retrogradely labeled neurons throughout ventral DLMDL
(open circles); dashed lines delineate
DLMDL from DLMVM. A small number of neurons
were also labeled within DLMVM as a result of both tracers
extending into small parts of lMANshell. Scale bar, 500 µm.
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Figure 4.
Photomicrographs demonstrating comparable patterns
of connectivity within the DLMVMlMANshell
projection in adult, 35 d, and 20 d birds. Injections of RDA
into the lateral part of left lMANshell (shown in
schematics on the left) resulted in retrograde label
within coronal sections (on right). A,
Retrogradely labeled cells in the ventromedial region of
DLMVM in an adult bird; faint FDA-labeled neurons can also
be seen in DLMDL in this photomicrograph because FDA, which
was injected into lMANcore, emits a small amount of
fluorescence under rhodamine optics. B, C, Retrograde
label was present in ventrolateral and ventral intermediate parts of
DLMVM in a 35 and a 20 d bird, respectively. Scale
bar, 200 µm.
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Figure 5.
Photomicrographs of anterograde label over
coronal sections of RA resulting from injections of RDA into right
lMANcore showing patterns of connectivity within the
lMANcoreRA projection in adult, 35 d, and 20 d
birds (cf. Johnson et al., 1995). Nissl-defined boundaries of RA are
depicted by dashed outlines, and injection sites within
lMANcore for each bird are shown in schematics.
A, An injection of RDA into ventral intermediate and
lateral lMANcore produced anterograde label restricted to a
triangular region within the medial and central regions of RA in an
adult bird. B, Anterograde label localized to the
ventromedial subregion of RA produced by an injection into dorsolateral
lMANcore in a 35 d bird. C, An
injection of RDA within the dorsolateral subregion of
lMANcore which extended slightly into its intermediate
subregion in a 20 d bird produced anterograde label encompassing
both ventromedial and ventrolateral parts of RA. The only region devoid
of label within RA was the dorsal "cap" region. D,
An injection in the ventral intermediate subregion of
lMANcore of another 20 d bird produced anterograde
label throughout RA except for a very small region along its
ventrolateral border. Scale bar, 200 µm.
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Figure 6.
Photomicrographs comparing patterns of
connectivity within the projection from dorsomedial
lMANcore (shown in schematics on the left)
to the dorsal part of RA (coronal sections) in an adult and a 20 d
bird. A, The majority of RDA-labeled axons enter the
lateral margin of RA and arborize within the dorsal "cap" region in
an adult bird. B, An injection into the dorsomedial part
of lMANcore of a 20 d bird that extended slightly into
ventromedial lMANcore produced anterograde label over the
dorsal and intermediate part of RA as well as the underlying
ventromedial and ventrolateral parts. A very small region within the
dorsalmost part of RA in this bird was covered by very sparse
anterograde label. Scale bar, 200 µm.
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Figure 7.
Injections of RDA into different subregions
of right lMANcore (shown in schematics on the
left) produced anterograde label over specific regions
within coronal sections of Area X (schematics and photomicrographs).
A, An injection into dorsomedial lMANcore in
an adult bird resulted in anterograde label over the medial part of
Area X (dashed outlines delineate medial and dorsal
borders of Area X from the surrounding LPO). B, In a
20 d bird, an injection into intermediate lMANcore
produced anterograde label over the intermediate part of Area X. Arrows in both photomicrographs indicate RDA-labeled
axons from lMANcore that cross the fiber tract LMD to enter
and arborize within Area X. Scale bar, 200 µm.
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Figure 8.
Anterograde label over Ad (Nissl-defined borders
indicated by dashed outlines in coronal sections)
resulting from injections of RDA into the lateral part of left
lMANshell indicate that the lMANshellAd
circuit is comparable in an adult (A), a 35 d (B), and a 20 d (C)
bird. Schematic diagrams on the left demonstrate
injection sites. In all three birds, anterogradely labeled axons from
lateral lMANshell crossed the dorsal border of lateral Ad,
whereas others entered intermediate Ad and turned laterally to arborize
specifically within lateral Ad (also see inset above
schematics of injection sites). Scale bar, 200 µm.
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Figure 9.
Photomicrographs depicting anterograde label over
lateral LPO resulting from injections of RDA into the lateral part of
left lMANshell in adult (A), 35 d (B), and 20 d (C)
birds. Inset (above schematics showing injection sites)
depicts a coronal section of the brain at the level of lMAN/Area X
showing RDA-labeled arbors in the ventrolateral aspect of LPO. The
lMANshellLPO circuit has not been reported previously.
Scale bar, 200 µm.
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Figure 10.
Schematic cross sections of the telencephalon at
two different levels demonstrating overall patterns of topography
within the efferent targets of lMANcore (Area X and RA) and
lMANshell (LPO, Ad, and dNCL) in an adult zebra finch after
injections of fluorescent tracers into different subregions of lMAN
core and shell. Injections of tracers into lateral and medial
lMANcore (right hemisphere in A) produced
anterograde label over corresponding lateral and medial subregions of
right Area X (cf. Vates and Nottebohm, 1995). B, These
injections also produced label restricted to the ventromedial and
dorsal subregions of ipsilateral RA, respectively (cf. Johnson et al.,
1995). Injections of fluorescent tracers into lateral and medial
subregions of lMANshell (left hemisphere in
A) resulted in anterograde label over lateral and medial
parts of LPO, respectively. B, Left hemisphere,
Anterograde label was also localized over the lateral parts of Ad and
dNCL from the injection into lateral lMANshell and over the
medial subregions of Ad and dNCL from injections into medial
lMANshell. Labeled lMANshell axons can be seen
traversing the terminal field within dNCL or travelling medial to it en
route to Ad. Injection sites in medial lMAN core and shell and the
resulting anterograde label are shown in black, whereas
injection sites in lateral lMAN core and shell and the resulting label
from these injections are shown in gray.
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Figure 11.
Photomicrographs showing anterograde label over
dNCL after injections of RDA into lMANshell.
A, An injection of RDA in the lateral part of
lMANshell in an adult bird produced terminal label in
lateral dNCL. B, An injection of RDA into the
ventromedial lMANshell in a 35 d bird produced
anterograde label over medial dNCL, whereas C, lateral
dNCL, was labeled from an injection into ventrolateral
lMANshell in a 20 d bird. Injection sites are shown in
schematics (on left). Inset above
schematics of injections sites demonstrates anterograde label over
lateral (black) and medial (gray)
dNCL from injections into lateral and medial
lMANshell, respectively. Arrows in
the photomicrographs indicate lMANshell axons, which
traverse dNCL and ultimately arborize within Ad. Scale bar, 200 µm.
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Retrograde label in DLM
Adult birds
When one tracer was injected into lMANshell and the
other tracer into lMANcore on the same side, no
double-labeled neurons were observed within ipsilateral DLM, confirming
previous findings that the DLMDL lMANcore
and DLMVM lMANshell circuits are separate, parallel pathways (cf. Johnson et al., 1995). Dye injections confined to the lateral part of lMANcore produced retrogradely
labeled neurons within the ventralmost part of
DLMDL, whereas injections into intermediate and
medial subregions produced retrogradely labeled neurons in intermediate
and dorsal subregions of DLMDL overlying this ventral
subregion, respectively. Comparing the pattern of retrograde label
resulting from injections into different subregions of
lMANcore in adult birds also revealed that dorsoventral position of the injection sites did not contribute to differences in
label over DLMDL. Twenty-six of a total of 26 injections
into lMANcore (10 in lateral core, seven in intermediate
core, and nine in medial core) confirmed this pattern of label in adult birds. Figure 2A demonstrates retrograde label
confined to a cluster of neurons in the ventral and intermediate parts
of DLMDL resulting from an injection of RDA that was
centered in ventral intermediate lMANcore and also extended
slightly into lateral lMANcore. No neurons within
DLMVM or within more dorsal parts of DLMDL were labeled by this injection (compare Fig. 3).
In contrast to injections into lMANcore, injections
into the shell region of lMAN produced retrogradely labeled neurons
only within the ventromedial part of DLM. Twenty-one of 21 dye
injections into lateral lMANshell resulted in retrograde
label over the ventral part of DLMVM, whereas nine
of nine injections into medial lMANshell produced
retrograde label within the medial subregion of DLMVM. An
RDA injection into lateral lMANshell that produced
retrograde label in a restricted area within the ventromedial part of
DLMVM is shown in Figure 4A.
These results confirm previous findings of broad patterns of
topographic organization within both of the DLMlMAN circuits in
adult male zebra finches (Johnson et al., 1995). However, the pattern
of retrograde label in DLMDL resulting from injections of
fluorescent tracers into lMANcore observed in our study
indicated a more dorsoventral pattern of organization in DLM compared
with the more mediolateral DLM topography emphasized by Johnson et al.
(1995). Although our results indicated some degree of
mediolateral topography within the
DLMDLlMANcore circuit, the
dorsoventral axis of DLMDL appeared to be mapped out
primarily along the mediolateral axis within lMANcore. It
is possible that we found a slightly different pattern of label within
this circuit because our injections encompassed smaller subregions
within lMANcore.
Juvenile birds (35 and 20 d)
Injections of RDA and FDA into lMAN core and shell of juvenile
birds (35 and 20 d) revealed a pattern of retrograde label in DLM
comparable to that found in adults: injections into
lMANcore produced retrogradely labeled neurons in
DLMDL, whereas dye injections into
lMANshell retrogradely labeled neurons in
DLMVM. Double-labeled neurons were never seen in these
birds after injections of different dyes into lMANcore and
lMANshell on the same side, indicating that the
DLMDLlMANcore and
DLMVMlMANshell circuits exist as discrete
pathways at the initiation of song learning (18-22 d after hatching).
Twenty-five of 25 injections into lMANcore (nine lateral,
six intermediate, and 10 medial core injections) and 26 of 26 injections into lMANshell (16 lateral and 10 medial) of
20 d birds produced patterns of retrograde label in
DLMDL and DLMVM respectively, which were
comparable to those in adults. Furthermore, the projections from DLM to
lMAN core and shell remain as separate pathways at 35 d after
hatching (Figs. 2B, 4B), an age at
which there is a dramatic increase in the volume of the overall DLM
terminal field which encompasses lMANshell (Johnson and
Bottjer, 1992). Thus, despite the considerable axonal re-arrangement suggested by the growth of the projection of DLM to
lMANshell (Iyengar and Bottjer, 1998), axons of individual
DLM neurons still respect the boundaries of core and shell regions in
lMAN. Thirteen of 13 injections (eight lateral, two intermediate, and
three medial) into lMANcore and 15 of 15 injections (nine
lateral and six medial) into lMANshell of 35 d birds
were used to confirm these patterns of retrograde label in
DLMDL and DLMVM, respectively.
The topographic organization within each DLMlMAN circuit in juvenile
birds was comparable to the patterns of topography seen in adult males.
Injections of either tracer into lateral, intermediate, or medial
subregions of lMANcore in juvenile birds of both age groups
produced retrograde label restricted to ventral, intermediate, or
dorsal parts of DLMDL, respectively. An example of
this pattern of topography is seen in Figure 2, B and
C, where injections of RDA into lateral lMANcore
of a 35 and a 20 d bird produced restricted groups of retrogradely
labeled neurons in the midventral (Fig. 2B) and
lateroventral parts of DLMDL (Fig. 2C).
Retrograde label did not extend into dorsal and intermediate parts of
DLMDL in either of the juvenile birds, indicating that the
DLMDLlMANcore pathway is topographically
organized at both these ages in a manner similar to that seen in
adults. A 35 d bird received injections of both RDA and FDA into
medial and lateral subregions of lMANcore, respectively (Fig. 3). Camera lucida tracings of the resultant retrograde label in serial sections of DLMDL demonstrated a
primarily dorsoventral pattern that was also seen in adult birds: RDA
from medial lMANcore retrogradely labeled neurons primarily
in the dorsal aspect of DLMDL, whereas FDA from
lateral lMANcore retrogradely labeled neurons throughout
ventral DLMDL. A small number of neurons were also labeled
in DLMVM, resulting from tracers extending into small parts of dorsal lMANshell.
Small dye injections into lateral or medial subregions of
lMANshell in juvenile birds retrogradely labeled
neurons restricted to ventral and medial subregions of DLM,
respectively. Figure 4, B and C, demonstrates the
pattern of retrograde label in DLMVM produced by injections
of RDA into lateral lMANshell in juvenile birds at 35 and
20 d of age. In both cases, retrograde label was confined to a
restricted subset of neurons within the ventral part of
DLMVM. Comparisons of Figure 4, B and
C, with Figure 4A demonstrate that the
pattern of topographic organization in the DLMVMlMANshell of 35 and 20 d birds is
also comparable to that seen in adult birds. Overall, these findings
indicate that the topographic pattern seen within both DLMlMAN
circuits in adults is already present at the initiation of vocal
development (20 d) and is maintained throughout the course of song learning.
Anterograde label in RA, Area X, Ad, LPO, and dNCL
Topographic organization of the
lMANcoreRA circuit
Adult birds. The lMANcoreRA
circuit is topographically organized in adult male zebra finches such
that ventromedial, ventrolateral, and dorsal regions of RA receive
projections from lateral, intermediate, and medial subregions of
lMANcore, respectively (Johnson et al., 1995).
Eleven of 11 RDA injections into lMANcore (three
lateral, four intermediate, and four medial injections) in the present study confirmed this pattern of anterograde label over RA. We extended
this pattern of results to include five injections in intermediate-lateral lMANcore, all of which produced
label over medial and central parts of RA in adult birds. In addition,
two injections targeted to intermediate-medial lMANcore
produced label in dorsal RA as well as in small regions extending along
the medial and lateral borders just ventral to this dorsal "cap". A
comparison of anterograde label resulting from injections in
lMANcore in adult birds also revealed that dorsoventral
position of the injection sites did not contribute to differences in
label over RA. Specific examples of topographic patterns within the
lMANcoreRA circuit in adult birds will be described in
relation to the pattern of topography seen in this circuit in 20 d
birds in the following section.
Comparison between patterns of topography in
lMANcoreRA circuit in 20 d and adult birds. In
contrast to the restricted topographic pattern of the
lMANcoreRA circuit in adult male zebra finches, small
injections of RDA targeted to different subregions of
lMANcore in 20 d zebra finches produced a poorly
refined pattern of connectivity in RA. Whereas injections into specific
parts of lMANcore in adult birds produced anterograde label
localized to restricted subregions of RA, comparable injections into
lMANcore of 20 d birds produced label that ramified
much more extensively within RA. This pattern of results was seen in 19 of a total of 20 injections analyzed in 20 d birds (four lateral,
five intermediate, nine medial, and two lateral-intermediate
injections) in lMANcore.
For example, an injection into dorsolateral lMANcore that
also extended slightly into intermediate lMANcore in a
20 d bird produced anterograde label encompassing both
ventrolateral and ventromedial regions of RA (Fig. 5C). The
only region within RA that was completely devoid of anterograde label
in this bird was the dorsal cap, the area that receives projections
from the medial part of lMANcore in adult birds (Fig.
6A). A comparison of the pattern of label in RA
in this bird (Fig. 5C) with that of an adult bird that
received an injection of comparable size into lMANcore (Fig. 5A) demonstrates the
difference between the lMANcoreRA circuit at these two
ages. In the adult bird, a small dye injection into ventral regions of
lateral and intermediate lMANcore produced a terminal field
restricted to medial and central subregions of RA. Most of the labeled
axons from lMANcore neurons in this bird entered lateral
RA, whereas a small number of axons also entered its dorsal and
ventrolateral subregions. However, all labeled lMANcore
axons arborized in a restricted region within medial and central
portions of RA. Although these injections in the 20 d and adult
bird are matched for size and mediolateral site within lMANcore, the injection in the 20 d bird is
located within dorsal lMANcore as opposed to ventral
lMANcore in the adult bird. However, we observed no
tendency for the pattern of anterograde label within RA to vary as a
function of dorsoventral position of the injection site. For example,
all injections into lateral lMANcore of adult birds produce
labeled axon terminals in medial and/or ventral portions of RA,
regardless of their dorsoventral position.
A particularly striking example of the tendency of lMAN axons to ramify
throughout RA of 20 d birds is shown in Figure 5D. An RDA injection into a ventral-intermediate subregion of
lMANcore in this bird produced intense terminal label
throughout RA, excluding only a very small region along its
ventrolateral border. A similar injection into intermediate
lMANcore of an adult bird produced label restricted to the
ventrolateral part of RA (data not shown). Thus, in contrast to the
adult pattern, small regions of lMANcore project to
relatively large target regions in RA, such that groups of neurons
within adjacent subregions of lMANcore in 20 d birds have overlapping terminal fields that encompass a large proportion of
RA. In fact, if comparable specificity of matching between afferent
inputs and target regions was to be preserved at both ages, the
terminal field of lMANcore axons would have to be much smaller in absolute size in juveniles than in adults because the overall size of RA is much smaller in 20 d birds (see Discussion).
Additional examples demonstrate further that the tendency of
lMANcore neurons to project to a relatively large region
within RA in 20 d birds was not restricted to a particular
subregion within lMANcore. An injection of RDA into the
dorsomedial part of lMANcore that also extended slightly
into ventromedial lMANcore in a 20 d bird labeled
axonal arbors throughout dorsal and intermediate RA with the exception
of a small region in dorsolateral RA that was very sparsely labeled
(Fig. 6B). Large parts of ventrolateral and
ventromedial RA were also anterogradely labeled by this injection. In
an adult bird with a comparable, albeit slightly smaller injection into
dorsomedial lMANcore, anterograde label encompassed
only dorsal RA (Fig. 6A). Thus, when injections were
(roughly) matched for dorsoventral as well as mediolateral sites within
lMANcore, anterograde label produced by these
injections was restricted to a much smaller proportion of RA in adults
as compared with 20 d birds.
Interestingly, the location of anterograde label produced by injections
into different sites within lMANcore also suggested that
the pattern of axonal connectivity from lMANcore to RA is different between 20 d and adult birds. That is, axon arbors of lMANcore neurons at 20 d were not preferentially
localized to the subregions within RA that they will ultimately
innervate in adulthood. For example, in Figure 5C, although
anterograde label fills the ventral two-thirds of RA in a 20 d
bird after an injection into the dorsal region of lateral and
intermediate lMANcore, the terminal field within
ventromedial RA is sparser than that within the ventrolateral part of
RA. In an adult, an injection within the ventral region of lateral and
intermediate lMANcore specifically labels the mediocentral
part of RA, whereas the ventrolateral subregion of RA is devoid of
label (Fig. 5A). Likewise, the injection site shown in
Figure 5D (into ventral-intermediate
lMANcore) would produce anterograde label in
ventrolateral RA of an adult bird, but this region of RA is the most
sparsely labeled in this 20 d bird. Overall, the results in
20 d birds indicate that the pattern of connectivity from
lMANcore to RA is less refined as compared with adult birds.
35 d birds. The topographic organization of the
lMANcoreRA circuit in 35 d birds was
comparable to the restricted pattern of topography in this circuit
present in adult birds as demonstrated by anterograde label over RA
produced by eight of eight RDA injections in lMANcore.
Of these injections, four were in lateral, two were in medial,
and two were in lateral-intermediate lMANcore. An RDA injection in the dorsolateral part of lMANcore in a 35 d bird produced a terminal field confined to ventromedial RA (Fig.
5B). Labeled axons could be seen traversing lateral and
dorsal regions of RA in this bird but they arborized only within
ventromedial RA. Interestingly, anterograde label in this 35 d
bird appears to be even more restricted compared with that seen in
the adult bird (Fig. 5A) that received an injection
into ventrolateral and intermediate lMANcore.
Furthermore, the size and location of this injection site are well
matched to that shown for a 20 d bird in Figure 5C, but
the resultant patterns of anterograde label are dramatically different.
That is, the proportion of RA encompassed by labeled axon terminals is
much higher in the 20 d bird, and the location of the terminal
field is not centered in ventral or medial regions of RA, as would be
expected for an injection site into lateral lMANcore in
older birds. These findings indicate that patterns of topography within
the lMANcoreRA circuit vary depending on the age of the
bird: whereas small subgroups of lMANcore neurons have
overlapping terminal fields within RA at 20 d, these terminal
fields are restricted within different subregions of RA by 35 d.
In addition, fluorescent tracer injections into different subregions of lMANcore of 35 d birds produced label
specifically within corresponding regions of RA, which matched the
pattern of topography seen in adults. Thus, the
lMANcoreRA circuit becomes topographically refined to
match the adult pattern between 20 and 35 d in male zebra finches,
during early stages of song learning.
Topographic organization of the
lMANcoreX circuit
Adults. Neurons in lMANcore also make a
topographic projection to Area X, a nucleus within the avian basal
ganglia (Nixdorf-Bergweiler et al., 1995; Vates and Nottebohm, 1995).
That is, neurons along the dorsal extent of lMANcore
project to dorsal parts of Area X, whereas neurons in more ventral
parts of lMANcore project to the ventral part of Area
X. In the present study, we found that 18 of 18 RDA injections into
lateral (n = 8), intermediate (n = 4),
or medial (n = 6) parts of lMANcore
produced patches of anterograde label largely confined to corresponding
lateral, intermediate, and medial subregions of Area X, confirming and
extending the pattern of topographic connectivity in this pathway.
Anterograde label over the dorsomedial part of Area X from an RDA
injection into the dorsomedial region of lMANcore is shown
in Figure 7A. Labeled axons from neurons in dorsomedial
lMANcore crossed the fiber tract lamina medullaris dorsalis
(LMD) (Fig. 7A, arrowheads), which lies ventral
to lMANcore and arborized within the dorsomedial part of
Area X.
Juvenile birds (35 and 20 d). Eight of eight injections
of RDA into different subregions of lMANcore in 35 d
(six in lateral and two in medial core) and 20 of 20 injections in
20 d birds (seven in lateral, four in intermediate, and nine in
medial core) produced anterograde label mainly within lateral,
intermediate, and medial regions of Area X, showing that the
lMANcoreArea X pathway displays coarse topographic
organization throughout song learning. An injection into intermediate
lMANcore of a 20 d bird produced anterograde label
largely confined to the intermediate part of Area X (Fig.
7B). As in adults, axons from neurons within intermediate
lMANcore in this bird did not arborize extensively within
either lateral or medial subregions of Area X or in any part of LPO.
This result is somewhat surprising in view of the fact that individual
lMANcore neurons send axon collaterals to both RA and Area
X (Nixdorf-Bergweiler et al., 1995; Vates and Nottebohm, 1995).
Therefore, the present results indicate that axon collaterals to RA are
not specifically restricted to their ultimate target fields, whereas
axon collaterals to X appear to be topographically restricted at
20 d (despite the smaller size of Area X in 20 d birds
compared with adults). It should be noted that the same injections in
20 d birds that did not give evidence of developmental differences
in axon targeting from lMANcoreArea X or from
DLMDLlMANcore did show differences in
topographic specificity from lMANcoreRA. That is,
identical injections (i.e., within the same bird) produce the same
topographic pattern of retrograde label in DLMDL and of
anterograde label in Area X between 20 d and adulthood, but
nevertheless produce a less refined pattern of anterograde label in RA
at 20 d than in adulthood. This pattern also underscores our
conclusion that the relative lack of topographic specificity in the
lMANcoreRA projection of 20 d birds does not reflect specific injection sites.
Topographic organization of the
lMANshellAd circuit
Adult birds. Seventeen of 17 injections of RDA into
lateral (n = 10) or medial (n = 7)
lMANshell produced anterograde label over lateral or medial
subregions of ipsilateral Ad, respectively. Figure 8A
shows anterograde label within the lateral part of Ad resulting from an
injection of RDA into lateral lMANshell of an adult bird.
Some of the labeled axons crossed the dorsolateral border of Ad and
entered lateral Ad directly whereas others entered dorsal intermediate
Ad and then turned laterally before arborizing specifically within
lateral Ad. Thus, the topographic projections between
lMANshellAd in adult males seen in this study were
comparable to those described by Johnson et al. (1995) (compare Fig.
10B).
Juvenile birds (35 and 20 d). Injections of RDA into
lMANshell of 35 d (seven of seven injections analyzed;
four in lateral and three in medial shell) and 20 d birds (17 of
17 injections; 10 in lateral, seven in medial shell) produced patterns
of anterograde label similar to those seen in normal adults. That is,
fluorescent tracer injections into lateral and medial
lMANshell produced anterograde label over corresponding
lateral and medial parts of Ad, which matched the patterns of
connectivity in the lMANshellAd circuit of adult male
birds. RDA injections into lateral lMANshell in a 35 and a
20 d bird produced labeled axons that crossed the dorsal border of
Ad and arborized within its lateral subregion (Fig. 8B,C, respectively), which was
comparable to the organization of the lateral
lMANshelllateral Ad present in adult birds (Fig. 8A).
Topographic organization of the
lMANshellLPO circuit
Adult birds. Ten of 10 injections that were restricted
to lateral lMANshell and seven of seven injections in
medial lMANshell also gave rise to anterogradely labeled
axons that crossed LMD and arborized within corresponding lateral and
medial regions of LPO (LPO is the medial striatal region of the avian
basal ganglia which includes Area X, shown diagrammatically in Fig.
10A). Some of the RDA-labeled axons from neurons in
lMANshell traversed Area X after crossing LMD but all of
them arborized solely within specific regions of LPO. Anterograde label
within LPO produced by injections into lMANshell was never
as intense as that in Area X produced by injections into
lMANcore, suggesting that the projection from lMANcore to Area X may be more robust than the
lMANshellLPO circuit. Figure 9A demonstrates
anterograde label over the lateral part of LPO after an injection of
RDA into lateral lMANshell of an adult bird. These
topographically organized lMANshellLPO circuits in male
zebra finches have not been described previously.
Juvenile birds (35 and 20 d). The
lMANshell LPO projection was also present in 35 and
20 d birds and was topographically organized. Injections of RDA
into the lateral region of lMANshell in a 35 d and in
a 20 d bird anterogradely labeled axons that crossed LMD and
produced terminal fields in lateral LPO (lateral to Area X; Fig.
9B,C) that were comparable to that present in an adult bird
with a similar injection in lateral lMANshell (Fig. 9A). Similarly, RDA injections into medial
lMANshell in juvenile birds of both ages produced
anterograde label over medial LPO (data not shown). Seven of seven
injections in 35 d birds of which four were in lateral and three
in medial lMANshell and 17 of 17 injections in
lMANshell of 20 d birds (10 in lateral and seven in
medial shell) demonstrated these patterns of topography.
Topographic organization of the
lMANshelldNCL circuit
Adult birds. In addition to anterograde label over LPO
and Ad, 17 of 17 injections of RDA into lMANshell also
produced a large terminal field in dNCL, a cortical region situated
caudolateral to HVC at the level of RA and Ad. This projection from
lMANshell to dNCL has also not been described previously
(Figs. 10B, 11A). Although some
lMANshell axons that terminate in Ad pass medially to the
dNCL terminal field, many axons from lMANshell neurons traverse this terminal field en route to Ad, as depicted in Figures 10B and 11A (arrows).
The lMANshelldNCL circuit also showed broad patterns of
topography, as 10 of 10 RDA injections into lateral lMANshell produced label over more lateral parts of dNCL,
whereas seven of seven injections into medial lMANshell
produced anterograde label over medial dNCL. The existence of this
pathway has been confirmed by J. D. Brady, B. E. Cribbs, and S. W. Bottjer (unpublished data), who made injections of RDA into dNCL and
observed retrogradely labeled neurons in lMANshell. Thus,
in addition to the projection from lMANshell to Ad, the
present results reveal that lMANshell has two novel
efferent targets, LPO and dNCL, and both lMANshellLPO and lMANshelldNCL circuits are topographically organized.
Juvenile birds (35 and 20 d). The
lMANshelldNCL projection was also present in juvenile
zebra finches and was comparable to the pathway seen in adult males.
Seven of seven injections into lMANshell in 35 d birds
(four in lateral and three in medial shell) and 17 of 17 injections
into lMANshell in 20 d birds (10 in lateral and seven
in medial shell) confirmed these results. Figure 11C shows a
terminal field of label in dNCL produced by an injection into
ventrolateral lMANshell in a 20 d bird. Labeled axons
from ventrolateral lMANshell in 20 d birds
(arrows) traversed dNCL before arborizing in Ad, a pattern
of organization similar to that seen in adults. In a 35 d bird, an
injection of RDA into ventromedial lMANshell produced a
terminal field in the medial region of dNCL (Fig.
11B). Labeled axons from ventromedial
lMANshell neurons, which terminated in medial Ad, traversed
this terminal field in dNCL before descending toward Ad. These
findings indicate that broad patterns of axonal connectivity
between lMANshell and Ad, LPO, and dNCL in 20 d,
35 d, and adult birds are comparable. Therefore, the
lMANshellAd, lMANshellLPO, and
lMANshelldNCL projections are already established at the
onset of song learning and are topographically organized in a manner
similar to that seen in adults.
Quantitative analysis of the lMANcoreRA circuit
As described above, anterograde label produced by small injections
of RDA into lMANcore in 20 d birds encompassed a
considerably greater proportion of RA than did comparable injections in
35 d or adult birds. This finding indicates that groups of neurons within lMANcore tend to have overlapping terminal fields in
20 d birds but not in 35 d or adult birds. To confirm that
the results we observed were not merely a reflection of the volume or
location of the injection within lMANcore, we
quantified the difference in the lMANcoreRA circuit in
20 d, 35 d, and adult birds only from well defined
lMANcore injection sites as well as the terminal fields in
RA that these injections produced (see Materials and Methods). The
results, shown in Table 2, reinforce our conclusion that comparable dye
injections into lMANcore of 20 d birds produce label
over a much greater proportion of RA compared with 35 d and adult
birds. These changes in the lMANcoreRA circuit are even
more striking given the fact that dye injections of similar size across
different ages should, if anything, label fewer lMANcore projection neurons in 20 d versus adult birds (Nordeen et al., 1992; Nixdorf-Bergweiler et al., 1995) (also see Materials and Methods,
section on Analysis). For example, comparably sized injections of RDA
were made in the medial part of lMANcore in a 20 d
bird (Pu511) and an adult bird (Bk311). Although the resultant volume of anterograde label within RA was smaller in the 20 d bird than in the adult, the proportion of RA occupied by anterograde label was
substantially higher in the 20 d bird (98%) as compared with the
adult (39%). A similar comparison can also be made for Pu514 lt (a
20 d bird) and the adult bird W421 with injections in
medial-intermediate lMANcore. Despite comparably sized
injections that produced (in these cases) similar volumes of
anterograde label in RA, the proportion of RA covered by labeled axons
was considerably higher in the 20 d bird (72%) than in the adult
bird (36%). These findings indicate that the proportion of RA occupied
by the labeled lMANcore terminal field is substantially
higher in 20 d than in adult birds and that these differences do
not reflect variations in injection volume or injection site within
lMANcore.
Across all injections, the percentage of RA volume occupied by labeled
lMANcore axons was substantially larger in 20 d birds (65%) compared with adult birds (37%) and 35 d birds (22%)
(F(2,24) = 23.8; p < 0.0001). Planned comparisons showed that the proportion of RA occupied
by anterogradely labeled axon arbors was higher in 20 d birds than
in either 35 d or adult birds (both p < 0.05). Although the proportion of RA occupied by labeled axons was lowest in
35 d birds, this value was not significantly lower when compared with adults (p > 0.05).
The volume of RA increases greatly over the course of song learning,
caused primarily by an increase in spacing between a stable number of
neurons (F(2,24) = 27.7; p < 0.0001, see Table 2) (cf. Konishi and Akutagawa, 1985; Bottjer et
al., 1986; Herrmann and Bischof, 1986; Nordeen and Nordeen,
1988a,b). Although the proportion of RA covered by the
lMANcore terminal field was substantially larger in 20 d birds versus adults and 35 d birds, the total volume of the
lMANcore terminal field was smaller in juvenile birds than in adults (overall F(2,24) = 3.72;
p = 0.04). Table 2 shows that the size of the terminal
field in RA across all injection sites was ~30% larger in adults
than in 20 d birds (0.108 vs 0.082 mm3),
although this difference was not statistically significant (p > 0.05). The size of the terminal field was
smallest in 35 d birds (0.059 mm3), and this
value was significantly less than that observed in adults
(p < 0.05) but not in 20 d birds
(p > 0.05). Because of the substantial growth
in the overall volume of RA between 20 and 35 d, the targeting of
labeled axon terminals to restricted subregions of RA was therefore
greatest in 35 d birds (i.e., a smaller terminal field was
localized within an expanding postsynaptic target). Because the total
number of lMANcore projection neurons remains constant
throughout song learning (Nordeen et al., 1992), any change in the
lMANcore terminal field would have to occur at the level of
individual axon arbors of lMANcore neurons in RA. Our
results indicate that the absolute volume of the lMANcore terminal field is small at 20 d and decreases somewhat by 35 d as RA grows, suggesting that individual lMANcore
terminals in RA may undergo remodeling and regression between 20 and
35 d, resulting in a refinement of the axonal connection between
these two nuclei. The lMANcore terminal field then expands
to match its expanding target after 35 d to achieve its adult configuration.
Quantitative analysis of the lMANcoreX circuit
In contrast to the lMANcoreRA circuit, which is
poorly refined at the onset of song learning (20 d), overall patterns
of connectivity from lMANcore neurons to Area X at 20 d were similar to those seen at 35 d and adulthood. The proportion
of Area X volume occupied by the lMANcore terminal field
was only slightly higher in 20 d birds (20%) compared with adult
birds (16%) across all injection sites within
lMANcore, and this difference was not significant
(F < 1; see Table 3). Comparing anterograde label produced by RDA injections of similar size and location within lMANcore in 20 d and adult birds revealed a similar
trend. For example, injections of comparable volume were made into the
medial part of lMANcore in a 20 d bird (Pu511) and an
adult (Bk311). Although the overall volume of the terminal field was
smaller in the 20 d bird than in the adult, the proportion of Area
X volume occupied by anterograde label from lMANcore (31%)
was slightly higher than that in the adult (24%). However, inspection
of Table 3 shows that the percentage of Area X occupied by the
lMANcore terminal field was highly variable within both
20 d and adult birds, such that the range of overlap between the
two groups was considerable. The absence of a significant difference
between the percentage of Area X occupied by lMANcore
terminals at 20 d compared with adult birds substantiates our
qualitative observations of the similarity between broad patterns of
topographic organization within the lMANcoreArea X
circuit throughout song learning.
The overall volume of Area X expands greatly between 20 d and
adulthood (F(1,16) = 63.0;
p < 0.0001, Table 3) (cf. Bottjer et al., 1985;
Nordeen and Nordeen, 1988a,b). Our results therefore suggest
that axon arbors of lMANcore neurons projecting to Area X
are extensively remodeled throughout song learning to maintain a
correct "topographic alignment" within their expanding target, because the broad pattern of topographic organization of this circuit
is comparable in 20 d and adult birds (a situation reminiscent of
the retinotectal projection in frogs) (Reh and Constantine-Paton, 1984;
Cline and Constantine-Paton, 1990). Whereas the percentage of Area X
occupied by the lMANcore terminal field is roughly
comparable at 20 d and adulthood, the absolute volume of
anterograde label within Area X tends to be smaller in 20 d birds,
although this difference was not significant
(F(1,16) = 1.16; p = 0.30).
This pattern also suggests that modifications within individual
lMANcore axon arbors act to maintain topographic
connections within Area X throughout song learning. Specifically, the
dramatic growth in the overall size of Area X suggests that individual
lMANcore arbors may grow to match their postsynaptic
target. Thus, topographic projections between lMANcore and
its targets RA and Area X must both be remodeled during song learning,
albeit to different degrees and perhaps by different mechanisms.
| |
DISCUSSION |
Our results show that axonal connections to and from lMAN are
present in juvenile male zebra finches at the onset of song learning
(20 d) and are, in most instances, topographically similar to their
counterparts in adult birds that have completed the acquisition of
stable song patterns. The present experiments provide ample evidence of
the similarity of broad patterns of topography within most song-control
circuits in juvenile and adult birds, although they obviously do not
preclude fine-grained rearrangements (e.g., at the level of individual
arbors; cf. Iyengar and Bottjer, 1998). Nevertheless, it is striking
that broad patterns of axonal connectivity between subsets of neurons
are so similar throughout the period for vocal learning, during which
time experience is of paramount importance in acquiring and refining
vocal patterns and song-control circuits are undergoing gross
morphological changes (Johnson and Bottjer, 1992). These results
indicate that the initial development of coarse topographic
organization in song-control circuits of zebra finches is independent
of experiences associated with vocal learning, suggesting that the
basic scaffolding of song-control circuitry may be specified innately
and serve as a necessary prerequisite for vocal learning (Burek et al.,
1991; Bottjer, 1997; Bottjer and Arnold, 1997; Iyengar et al., 1997;
cf. Seidenberg, 1997). This pattern underscores the inherent ability of
the nervous system to establish highly organized patterns of
connectivity (Goodman and Shatz, 1993; Tessier-Lavigne and Goodman,
1996; Feldman and Knudsen, 1997). The fine details of these highly
organized patterns of innate connections are modified and/or maintained
by experiential factors in many neural systems (Wallhaüser-Franke
et al., 1995; Crair et al., 1998).
Behavioral evidence has suggested that innately specified circuits form
templates that contain pre-encoded information about conspecific song
(Marler, 1997; Whaling et al., 1997; cf. Bottjer, 1997). These innate
templates may serve to guide the generation of incipient vocalizations
while juvenile birds refine their song patterns during sensorimotor
integration. Song production in juvenile birds that have been deafened
or placed in social isolation without access to a tutor's song is
abnormal, but retains some species-specific characteristics (Konishi,
1965; Immelman, 1969; Marler and Sherman, 1983; Eales, 1985, 1987).
Perhaps the songs of acoustically isolated birds are guided by
circuitry that contains information concerning some basic
characteristics of conspecific song. Our results, indicating that broad
patterns of axonal connectivity to and from lMAN are established early
in development, suggest that these pathways may be candidates for such
innately specified circuits.
Broad topographic patterns within the lMANcoreRA
circuit are refined during the early stages of song learning
A striking exception to the adult-like pattern of organization
seen in most circuits during early stages of song learning was provided
by the lMANcoreRA projection. In adult and 35 d birds, small groups of neurons within specific subregions of
lMANcore project to restricted groups of postsynaptic
target cells in RA. In 20 d birds, neurons within specific
subregions of lMANcore project to a much larger proportion
of RA, and broad patterns of connectivity within the
lMANcoreRA circuit tend to differ from the adult
pattern. Thus, overall topography within the
lMANcoreRA circuit is poorly refined at 20 d,
and neurons within different subregions of lMANcore have
overlapping terminal fields within RA at this age. RA contains a
myotopic map of the syrinx (Vicario, 1991; Wild, 1993a, 1997), and this
map may be preserved upstream in the
DLMDLlMANcoreRA circuit (Johnson et al.,
1995; Vates and Nottebohm, 1995). The refinement in topographic
connectivity of the lMANcoreRA circuit during early
stages of song development therefore suggests an increase in refinement
of vocal motor control that may be reflected in song behavior. During
early stages of song learning, juvenile swamp sparrows sing a large
number of notes (subsong) of which only a small number are retained in
the adult song, and the morphology of individual notes becomes
increasingly stereotyped (Marler and Peters, 1982). Our findings are
therefore consistent with the idea that the emergence of coarse
topography within the lMANcoreRA circuit at 35 d
signifies a behavioral transition, perhaps reflecting in part the
initial transition from subsong to plastic song and pruning of the
vocal repertoire (cf. Marler, 1991; Margoliash, 1997; Nordeen and
Nordeen, 1997).
What mechanisms underlie these developmental changes in the
lMANcoreRA circuit? The number of neurons in male RA is
thought to be fixed by ~20 d, although the overall size of RA
increases greatly during vocal development: the density of neurons in
RA is high at 20 d, but thereafter the size and spacing of RA
neurons increases over the course of song learning, leading to a
substantial increase in RA volume during this period (Konishi and
Akutagawa, 1985; Bottjer et al., 1986; Herrmann and Bischof, 1986;
Nordeen and Nordeen, 1988a; Kirn and DeVoogd, 1989). The smaller size of RA in 20 d birds has interesting implications for patterns of
topographic specificity, in that small groups of lMAN neurons would
have to project to even more restricted areas of RA than at older ages
to preserve similar patterns of axonal connectivity. The present
results show that this is clearly not the case. Although the absolute
volume occupied by labeled axons from lMANcore is much
smaller in 20 d than in adult birds (Table 2), the proportion of
RA occupied by this terminal field is nevertheless the largest at
20 d because of the much smaller size of RA at this age. Because the number of lMANcore projection neurons remains constant
throughout song learning (Nordeen et al., 1992), the developmental
changes that we observed in their terminal field within RA presumably occur at the level of individual lMANcore axon arbors.
Thus, our results suggest that axon terminals of single
lMANcore neurons overlap to a greater extent at 20 d
than at 35 d or adulthood.
In contrast to the relative lack of specificity in the
lMANcoreRA projection at 20 d, the restriction of
lMAN axons to specific regions within RA may be greatest in 35 d
birds, as evidenced by the slight decrease in the size of the
lMANcore terminal field within an expanding RA at this age.
Interestingly, 35 d birds appear to be at the height of the
sensitive period for learning notes from a tutor song model (Immelmann,
1969; Böhner, 1990; Zann, 1990; Slater et al., 1993). Thus,
whatever information is being mapped within the
lMANcoreRA circuit, the degree of refinement or the
grain of this map may be the best around the time when birds are
acquiring a memory of song sounds. After 35 d, continued remodeling of axon terminals may give rise to the adult pattern of
connectivity within the lMANcoreRA circuit. The idea
that lMANcoreRA axon terminals undergo axonal remodeling
and synaptic rearrangements during the period of song learning is
supported by the finding that the number of synapses made by
lMANcore axons onto RA neurons decreases substantially over
the course of vocal development (Herrmann and Arnold, 1991).
Interestingly, although axon remodeling also plays a role in the
refinement of circuits in other neural systems, such remodeling is
usually accompanied by an increase in synapse number (Purves and
Lichtman, 1985; O'Leary et al., 1986; O'Rourke and Fraser, 1986;
Sretavan and Shatz, 1986; Cline and Constantine-Paton, 1990; Campbell
and Shatz, 1992; Simon and O'Leary, 1992; Antonini and Stryker, 1993;
Roskies et al., 1995; Krug et al., 1998).
Broad topographic patterns within the lMANcoreX
circuit are adult-like at the onset of vocal learning
Individual RA-projecting neurons within lMANcore also
send an axon collateral to Area X in adult male zebra finches
(Nixdorf-Bergweiler et al., 1995; Vates and Nottebohm, 1995). We found
that axon arbors of lMANcore neurons formed topographically
restricted projections within Area X at 20 d, comparable to those
in adults. This is a striking finding, considering that axon
collaterals of the same neurons that arborize within the "correct"
topographic region of Area X at 20 d fail to innervate a
restricted subset of RA neurons with any great precision. This finding
suggests that postsynaptic target factors may contribute to differences
in establishment of overall topography within
lMANcoreArea X and lMANcoreRA circuits during song learning. It should be stressed however, that although coarse topography is present throughout song learning in the
lMANcoreArea X projection, this circuit must be actively
remodeled during this time to preserve overall topography in the face
of dramatic growth of Area X.
The finding that axon collaterals of lMANcore neurons
maintain a more restricted pattern of arborization within Area X than in RA of 20 d birds raises the question of whether this difference has a functional correlate in song behavior. Interestingly, inputs to
RA from HVC change substantially during song learning, whereas HVC
inputs to Area X appear to be conserved. Newly generated HVC neurons
send axons down to RA in both developing zebra finches and adult
canaries as new song patterns are learned, whereas the projection of a
separate population of HVC neurons to Area X is stable (i.e., these
neurons are born in ovo and are not replaced by new neurons)
(Alvarez-Buylla et al., 1988; Nordeen and Nordeen, 1988b). This pattern
provides an interesting correlate to the results of the present study
and may reflect the fact that RA is directly on-line for vocal
production, and hence remodeling of inputs to RA (from both lMAN and
HVC) may be necessary to encode a specific vocal pattern. In contrast,
Area X may be involved in basic aspects of vocal learning (Sohrabji et
al., 1990; Scharff and Nottebohm, 1991; Jarvis et al., 1998), but is
presumably not part of the direct motor pathway for song production.
Thus, stability of topographic inputs to Area X from lMAN may be
required in order for this circuit to serve some learning function (as
opposed to encoding the program for execution of the learned behavior).
Loops within song control circuits: analogies to mammalian
basal ganglia
Patterns of topography within the
DLMDLlMANcore and
DLMVMlMANshell circuits at 20 d were
comparable to those in adult birds. The efferent projections of
lMANshell were also topographically organized throughout
vocal learning. We found that lMANshell neurons project not
only to Ad, but also to LPO and dNCL, newly described projections that
parallel the lMANcoreArea X circuit and mMANHVC circuits, respectively (Nottebohm et al., 1982; Foster et al., 1997;
Foster and Bottjer, 1998) (Fig. 12).
The presence of the lMANshellLPO circuit has been
confirmed by Brady, Cribbs, and Bottjer (unpublished observations), who
found that small injections of dye into Ad backfill a spatially
restricted subset of neurons within lMANshell, which
in turn send axon collaterals into restricted regions of LPO. Thus, the
same subset of lMANshell neurons that project to Ad also
project to LPO and provide pathways that are parallel to the
lMANcoreRA/Area X connections.
View larger version (22K):
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|
Figure 12.
Schematic of the major connections of core and
shell, showing a remarkable degree of similarity in the overall
patterns of connectivity within the projections to and from
lMANcore and lMANshell. In addition to the
DLMDLlMANcoreRA and
DLMVMlMANshellAd projections, which
parallel each other (Johnson et al., 1995), the
lMANcoreArea X circuit (Vates and Nottebohm, 1995)
mirrors the lMANshellLPO circuit (present study). Both
Area X and LPO project to the thalamic nucleus DLM (Bottjer et al.,
1989; S. Iyengar and S. W. Bottjer, unpublished observations),
forming loops that may provide feedback about song to the rest of the
song control circuitry. The RA/AdDLMlMAN loops (Wild, 1993b;
Brady, Cribbs, and Bottjer, unpublished observations) may be
important for integrating descending motor output (RA)
and diverse kinds of sensory information (Ad, see below)
with song learning. Both Area X and RA of the core pathway receive
afferent input from the higher vocal center (HVC) (Nottebohm et al.,
1976), which is paralleled by analogous projections from dNCL onto LPO
and Ad within the shell pathway (Brady, Cribbs, and Bottjer,
unpublished observations). Additionally, the mMANHVC circuit within
the core projection (Nottebohm et al., 1982; Foster et al., 1997;
Foster and Bottjer, 1998) is mirrored by the
lMANshelldNCL circuit (present study) within the shell
pathway. Interestingly, the AdSN/AVT circuit (Brady, Cribbs, and
Bottjer, unpublished observations), which provides dopaminergic input
to Area X and LPO (Lewis et al., 1981), may influence both core and
shell pathways. Links between these two pathways are also provided by
the RA/AdDLM/DMPlMAN/mMAN projections (Foster et al., 1997) (data
not shown), through efferent targets of mMAN, that is, HVC and Area X. LPO, Parolfactory lobe, the medial component of the
avian striatum; HVC, higher vocal center;
mMAN, medial magnocellular nucleus of the anterior
neostriatum; dNCL, caudolateral neostriatum;
DMP, dorsomedial nucleus of the posterior
thalamus.
|
|
Figure 12 demonstrates the "litany of loops" within the song
control system referred to by Bottjer and Johnson (1997), with some
additions based on recent findings. Interestingly, accruing evidence
supports the existence of two major subdivisions of lMAN circuitry into
distinct core and shell pathways, suggesting that each may process
different types of information or subserve different functions for
vocal learning. The majority of projections to and from the core and
shell regions of lMAN appear to be mirror images of one another,
suggesting some potential similarities in how information is processed
by these two pathways. Each of these pathways is characterized by
multiple feedback loops and multiple points of potential contact where
information may be integrated both within and between pathways. The
core pathway is apt to be directly involved with motor aspects of song
behavior, because the output of RA neurons goes directly to vocal motor
neurons. Interestingly, there is a dramatic increase in the overall
volume of lMANshell (Johnson and Bottjer, 1992) accompanied
by an increase in the refinement of individual DLMVM axon
arbors within this region between 20 and 35 d (Iyengar and
Bottjer, 1998). The time course of this growth and regression seems to
parallel the functional involvement of lMAN in vocal learning and
suggests that lMANshell may be actively involved in some
aspect of vocal learning at the height of the sensitive period for song
acquisition (Weinberger, 1995; cf. Bottjer, 1997). However, the
lMANshellAd pathway is unlikely to play any direct role
in vocal production because the output of Ad does not go to vocal motor
neurons (Brady, Cribbs, and Bottjer, unpublished observations). Both RA
and Ad send projections to a dorsal thalamic zone (including both DLM
and DMP), thereby creating potential feedback loops that may be
involved in integrating descending motor output and other kinds of
sensory information with song learning.
The large number of loops within song-control circuitry suggests a high
degree of feedback and integration at different levels within these
circuits (cf. Johnson and Bottjer, 1997). The overall XDLMlMAN
circuitry (both core and shell) is a basal gangliathalamuscortex pathway and appears to provide a classic example of parallel pathways characterized by both convergence (XDLM) and divergence
(DLMlMAN), suggesting strong similarities to the organization of
mammalian basal ganglia circuitry. This type of organization may
provide a neural strategy for expanding the amount of brain space
devoted to processing and analyzing multiple features of song-related information (cf. Graybiel et al., 1994). Both Area X and LPO are components of the avian basal ganglia (striatum) (Reiner et al., 1984)
and receive dopaminergic inputs from the substantia nigra (SN) and
ventral tegmental area (AVT) (Lewis et al., 1981; Bottjer, 1993).
Whereas the function of LPO in song learning has not been examined,
lesions of Area X in juvenile zebra finches disrupt vocal production
(Sohrabji et al., 1990; Scharff and Nottebohm, 1991). Whereas lesions
of Area X in adult birds do not disrupt song production, the act of
singing induces strong induction of the immediate early gene
ZENK in a context-dependent manner: ZENK is
induced only when birds are singing in isolation (practicing?), but not
when they are courting a female (Jarvis et al., 1998). Thus, the
XDLMlMAN pathway may be similar to mammalian basal ganglia
pathways in terms of an involvement in motor aspects of learning,
planning, and coordination of movement and motivation (Alexander et
al., 1986; Alexander, 1994; Graybiel et al., 1994, 1995a,b; Mink, 1996;
cf. Bottjer and Johnson, 1997).
| |
FOOTNOTES |
Received Jan. 19, 1999; revised April 28, 1999; accepted May 4, 1999.
This research was supported by National Institutes of Health Grant
DC00190. We thank Linh Ho for excellent technical assistance and Frank
Johnson for assistance with analysis of topography in adult birds.
Correspondence should be addressed to Soumya Iyengar, Department of
Biology, HNB 218, University of Southern California, Los Angeles, CA
90089-2520.
| |
REFERENCES |
-
Agmon A,
Yang LT,
O'Dowd DK,
Jones EG
(1993)
Organized growth of thalamocortical axons from the deep tier of terminations into layer IV of developing mouse barrel cortex.
J Neurosci
13:5365-5382[Abstract].
-
Agmon A,
Yang LT,
Jones EG,
O'Dowd DK
(1995)
Topological precision in the thalamic projection to neonatal mouse barrel cortex.
J Neurosci
15:549-561[Abstract].
-
Alexander GE
(1994)
Basal ganglia-thalamocortical circuits: their role in control of movements.
J Clin Neurophysiol
11:420-431[Web of Science][Medline].
-
Alexander GE,
DeLong MR,
Strick PL
(1986)
Parallel organization of functionally segregated circuits linking basal ganglia and cortex.
Annu Rev Neurosci
9:357-381[Web of Science][Medline].
-
Antonini A,
Stryker MP
(1993)
Development of individual geniculocortical arbors in cat striate cortex and effects of binocular impulse blockade.
J Neurosci
13:3549-3573[Abstract].
-
Alvarez-Buylla A,
Theelen M,
Nottebohm F
(1988)
Birth of projection neurons in the higher vocal center of the canary forebrain before, during, and after song learning.
Proc Natl Acad Sci USA
85:8722-8726[Abstract/Free Full Text].
-
Böhner J
(1990)
Early acquisition of song in the zebra finch.
Anim Behav
39:369-374.
-
Bottjer SW
(1993)
The distribution of tyrosine hydroxylase immunoreactivity in the brains of male and female zebra finches.
J Neurobiol
24:51-69[Web of Science][Medline].
-
Bottjer SW
(1997)
Building a bird brain: sculpting neural circuits for a learned behavior.
Bioessays
19:1109-1116.
-
Bottjer SW,
Arnold AP
(1997)
Developmental plasticity in neural circuits for a learned behavior.
Annu Rev Neurosci
20:459-481[Web of Science][Medline].
-
Bottjer SW,
Johnson F
(1997)
Circuits, hormones, and learning: vocal behavior in songbirds.
J Neurobiol
33:602-618[Web of Science][Medline].
-
Bottjer SW,
Sengelaub DR
(1989)
Cell death during development of a forebrain nucleus involved with vocal learning in zebra finches.
J Neurobiol
20:609-618[Medline].
-
Bottjer SW,
Miesner EA,
Arnold AP
(1984)
Forebrain lesions disrupt development but not maintenance of song in passerine birds.
Science
224:901-903[Abstract/Free Full Text].
-
Bottjer SW,
Glaessner SL,
Arnold AP
(1985)
Ontogeny of brain nuclei controlling song learning and behavior in zebra finches.
J Neurosci
5:1556-1562[Abstract].
-
Bottjer SW,
Miesner EA,
Arnold AP
(1986)
Changes in neuronal number, density and size account for increases in volume of song-control nuclei during song development in zebra finches.
Neurosci Lett
67:263-268[Web of Science][Medline].
-
Bottjer SW,
Halsema KA,
Brown SA,
Miesner EA
(1989)
Axonal connections of a forebrain nucleus involved with song learning in zebra finches.
J Comp Neurol
279:312-326[Web of Science][Medline].
-
Burek MJ,
Nordeen KW,
Nordeen EJ
(1991)
Neuron loss and addition in developing zebra finch song nuclei are independent of auditory experience during song learning.
J Neurobiol
22:215-223[Web of Science][Medline].
-
Campbell G,
Shatz CJ
(1992)
Synapses formed by identified retinogeniculate axons during the segregation of eye input.
J Neurosci
12:1847-1858[Abstract].
-
Catalano SM,
Robertson RT,
Killackey HP
(1991)
Early ingrowth of thalamocortical afferents to the neocortex of the prenatal rat.
Proc Natl Acad Sci USA
88:2999-3003[Abstract/Free Full Text].
-
Cline HT,
Constantine-Paton M
(1990)
NMDA receptor agonist and antagonists alter retinal ganglion cell arbor structure in the developing frog retinotectal projection.
J Neurosci
10:1197-1216[Abstract].
-
Crair MC,
Gillespie DC,
Stryker MP
(1998)
The role of visual experience in the development of columns in cat visual cortex.
Science
279:566-570[Abstract/Free Full Text].
-
Eales LA
(1985)
Song learning in zebra finches: some effects of song model availability on what is learnt and when.
Anim Behavior
33:1293-1300.
-
Eales LA
(1987)
Song learning in female-raised zebra finches: another look at the sensitive phase.
Anim Behav
35:1356-1365.
-
Feldman DE,
Knudsen EI
(1997)
An anatomical basis for visual calibration of the auditory space map in the barn owl's midbrain.
J Neurosci
17:6820-6837[Abstract/Free Full Text].
-
Foster EF,
Bottjer SW
(1998)
Axonal connections of the high vocal center and surrounding cortical regions in juvenile and adult male zebra finches.
J Comp Neurol
397:118-138[Web of Science][Medline].
-
Foster EF,
Mehta RP,
Bottjer SW
(1997)
Axonal connections of the medial magnocellular nucleus of the anterior neostriatum in zebra finches.
J Comp Neurol
382:364-381[Web of Science][Medline].
-
Goodman C,
Shatz CJ
(1993)
Developmental mechanisms that generate precise patterns of neuronal connectivity.
Cell
10[Suppl]:77-98.
-
Graybiel AM
(1995a)
The basal ganglia.
Trends Neurosci
18:60-62[Web of Science][Medline].
-
Graybiel AM
(1995b)
Building action repertoires: memory and learning functions of the basal ganglia.
Curr Opin Neurobiol
5:733-741[Web of Science][Medline].
-
Graybiel AM,
Aosaki T,
Flaherty AW,
Kimura M
(1994)
The basal ganglia and adaptive motor control.
Science
265:1826-1831[Abstract/Free Full Text].
-
Herrmann K,
Arnold AP
(1991)
The development of afferent projections to the robust archistriatal in male zebra finches: a quantitative electron microscopic study.
J Neurosci
11:2063-2074[Abstract].
-
Herrmann K,
Bischof HJ
(1986)
Delayed development of song control nuclei in the zebra finch is related to behavioral development.
J Comp Neurol
245:167-175[Medline].
-
Immelman K
(1969)
Song development in the zebra finch and other estrildid finches.
In: Bird vocalizations (Hinde RA,
ed), pp 61-77. Cambridge: Cambridge UP.
-
Iyengar S,
Bottjer SW
(1998)
Growth and regression in a thalamocortical projection during the sensitive period for vocal learning in zebra finches.
Soc Neurosci Abstr
24:1189.
-
Iyengar S,
Viswanathan SS,
Bottjer SW
(1997)
Development of topographic organization in neural circuits for vocal learning in zebra finches.
Soc Neurosci Abstr
23:1330.
-
Jarvis ED,
Scharff C,
Grossman MR,
Ramos JA,
Nottebohm F
(1998)
For whom the bird sings: context-dependent gene expression.
Neuron
21:775-788[Web of Science][Medline].
-
Johnson F,
Bottjer SW
(1992)
Growth and regression of thalamic efferents in the song-control system of male zebra finches.
J Comp Neurol
326:442-450[Web of Science][Medline].
-
Johnson F,
Sablan MM,
Bottjer SW
(1995)
Topographic organization of a forebrain pathway involved with vocal learning in zebra finches.
J Comp Neurol
358:260-278[Web of Science][Medline].
-
Kirn JR,
DeVoogd TJ
(1989)
Genesis and death of vocal control neurons during sexual differentiation in the zebra finch.
J Neurosci
9:3176-3187[Abstract].
-
Konishi M
(1965)
The role of auditory feedback in the control of vocalization in the white-crowned sparrow.
Z Tierpsychol
22:770-783[Medline].
-
Konishi M,
Akutagawa E
(1985)
Neuronal growth, atrophy and death in a sexually dimorphic song nucleus in the zebra finch brain.
Nature
315:145-147[Medline].
-
Krug K,
Smith AL,
Thompson ID
(1998)
The development of topography in the hamster geniculo-cortical projection.
J Neurosci
18:5766-5776[Abstract/Free Full Text].
-
Lewis JW,
Ryan SM,
Arnold AP,
Butcher LL
(1981)
Evidence for a catecholaminergic projection to Area X in the zebra finch.
J Comp Neurol
196:347-354[Web of Science][Medline].
-
Margoliash D
(1997)
Functional organization of forebrain pathways for song production and perception.
J Neurobiol
33:671-693[Web of Science][Medline].
-
Marler P
(1991)
Song-learning behavior: the interface with neuroethology.
Trends Neurosci
14:199-206[Web of Science][Medline].
-
Marler P
(1997)
Three models of song learning: evidence from behavior.
J Neurobiol
33:501-516[Web of Science][Medline].
-
Marler P,
Peters S
(1982)
Developmental overproduction and selective attrition: new processes in the epigenesis of birdsong.
Dev Psychobiol
15:369-378[Web of Science][Medline].
-
Marler P,
Sherman V
(1983)
Song structure without auditory feedback: emendations of the auditory template hypothesis.
J Neurosci
3:517-531[Abstract].
-
Mink JW
(1996)
The basal ganglia: focused selection and inhibition of competing motor programs.
Prog Neurobiol
50:381-425[Web of Science][Medline].
-
Nixdorf-Bergweiler BE,
Lips MB,
Heinemann U
(1995)
Electrophysiological and morphological evidence for a new projection of LMAN-neurones toward Area X.
NeuroReport
6:1729-1732[Web of Science][Medline].
-
Nordeen EJ,
Nordeen KW
(1988a)
Sex and regional differences in the incorporation of neurons born during song learning in zebra finches.
J Neurosci
8:2869-2874[Abstract].
-
Nordeen KW,
Nordeen EJ
(1988b)
Projection neurons within a vocal motor pathway are born during song learning in zebra finches.
Nature
334:149-151[Medline].
-
Nordeen KW,
Nordeen EJ
(1997)
Anatomical and synaptic substrates for avian song learning.
J Neurobiol
33:532-548[Web of Science][Medline].
-
Nordeen EJ,
Grace A,
Burek MJ,
Nordeen KW
(1992)
Sex-dependent loss of projection neurons involved in avian song learning.
J Neurobiol
23:671-679[Web of Science][Medline].
-
Nottebohm F,
Kelley DB,
Paton JA
(1982)
Connections of vocal control nuclei in the canary telencephalon.
J Comp Neurol
207:344-357[Web of Science][Medline].
-
O'Leary DD,
Fawcett JW,
Cowan WM
(1986)
Topographic targeting errors in the retinocollicular projection and their elimination by selective ganglion cell death.
J Neurosci
6:3692-3705[Abstract].
-
O'Rourke NA,
Fraser SE
(1986)
Dynamic aspects of retinotectal map formation revealed by a vital-dye fiber-tracing technique.
Dev Biol
114:265-276[Web of Science][Medline].
-
Purves D,
Lichtman JW
(1985)
Rearrangement of developing neuronal connections.
In: Principles of neural development, pp 271-300 Sunderland, MA: Sinauer.
-
Reh TA,
Constantine-Paton M
(1984)
Retinal ganglion cell terminals change their projection sites during larval development of Rana pipiens.
J Neurosci
4:442-457[Abstract].
-
Reiner A,
Davis BM,
Brecha NC,
Karten HJ
(1984)
The distribution of enkephalinlike immunoreactivity in the telencephalon of the adult and developing domestic chicken.
J Comp Neurol
228:245-262[Medline].
-
Roskies A,
Friedman GC,
O'Leary DD
(1995)
Mechanisms and molecules controlling the development of retinal maps.
Perspect Dev Neurobiol
3:63-75[Web of Science][Medline].
-
Scharff C,
Nottebohm F
(1991)
A comparative study of the behavioral deficits following lesions of various parts of the zebra finch song system: implications for vocal learning.
J Neurosci
11:2896-2913[Abstract].
-
Seidenberg MS
(1997)
Language acquisition and use: learning and applying probabilistic constraints.
Science
275:1599-1603[Abstract/Free Full Text].
-
Simon DK,
O'Leary DD
(1992)
Development of topographic order in the mammalian retinocollicular projection.
J Neurosci
12:1212-1232[Abstract].
-
Slater PJB,
Jones AE,
ten Cate CJ
(1993)
Can lack of experience delay the end of the sensitive phase for song learning?
Netherlands J Zool
40:80-90.
-
Sohrabji F,
Nordeen EJ,
Nordeen KW
(1990)
Selective impairment of song learning following lesions of a forebrain nucleus in the juvenile zebra finch.
Behav Neural Biol
53:51-63[Web of Science][Medline].
-
Sretavan DW,
Shatz CJ
(1986)
Prenatal development of retinal ganglion cell axons: segregation into eye-specific layers within the cat's lateral geniculate nucleus.
J Neurosci
6:234-251[Abstract].
-
Tessier-Lavigne M,
Goodman CS
(1996)
The molecular biology of axon guidance.
Science
274:1123-1133[Abstract/Free Full Text].
-
Vates GE,
Nottebohm F
(1995)
Feedback circuitry within a song-learning pathway.
Proc Natl Acad Sci USA
92:5139-5143[Abstract/Free Full Text].
-
Vicario DS
(1991)
Organization of the zebra finch song control system: II. Functional organization of outputs from nucleus Robustus archistriatalis.
J Comp Neurol
309:486-494[Web of Science][Medline].
-
Wallhaüsser-Franke E,
Nixdorf-Bergweiler BE,
DeVoogd TJ
(1995)
Song isolation is associated with maintaining high spine frequencies on zebra finch lMAN neurons.
Neurobiol Learn Mem
64:25-35[Web of Science][Medline].
-
Weinberger NM
(1995)
Dynamic regulation of receptive fields and maps in the adult sensory cortex.
Annu Rev Neurosci
18:129-158[Web of Science][Medline].
-
Wild JM
(1993a)
The avian nucleus retroambigualis: a nucleus for breathing, singing and calling.
Brain Res
606:319-324[Web of Science][Medline].
-
Wild JM
(1993b)
Descending projections of the songbird nucleus robustus archistriatalis.
J Comp Neurol
338:225-241[Web of Science][Medline].
-
Wild JM
(1997)
Neural pathways for the control of birdsong production.
J Neurobiol
33:653-670[Web of Science][Medline].
-
Whaling CS,
Solis MM,
Doupe AJ,
Soha JA,
Marler P
(1997)
Acoustic and neural bases for innate recognition of song.
Proc Natl Acad Sci USA
94:12694-12698[Abstract/Free Full Text].
-
Zann R
(1990)
Song and call learning in wild zebra finches in south-east Australia.
Anim Behav
40:811-828.
-
Zann RA
(1996)
Vocalizations.
In: The zebra finch. A synthesis of field and laboratory studies (Perrins CM,
ed), pp 196-247. New York: Oxford UP.
Copyright © 1999 Society for Neuroscience 0270-6474/99/19146037-21$05.00/0
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ABSTRACT
INTRODUCTION
