 |
 Previous Article | Next Article 
The Journal of Neuroscience, January 1, 2000, 20(1):375-386
Dependence of GABAergic Synaptic Areas on the Interneuron Type
and Target Size
Yoshiyuki
Kubota1 and
Yasuo
Kawaguchi1, 2
1 Laboratory for Neural Circuits, Bio-Mimetic Control
Research Center, The Institute of Physical and Chemical Research
(RIKEN), Moriyama, Nagoya 463-0003, Japan, and
2 Laboratory of Cerebral Circuitry, National Institute for
Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
 |
ABSTRACT |
In the neostriatum, several types of interneuron with distinct
firing patterns and expression of neuroactive substances are known to exist. We found two types of neostriatal interneurons, parvalbumin-containing fast-spiking (FS) cells and
somatostatin-containing low-threshold spike (LTS) cells to both
be immunoreactive for GABA at their axon terminals in immersion-fixed
brain slices from rat. To reveal the differences in synaptic
connections between these two types of GABAergic interneurons, the
postsynaptic target and their synaptic structure were compared by
three-dimensional reconstructions from electron microscopic images of
intracellularly stained axon terminals. FS cells made a greater
proportion of synaptic contacts onto somata than LTS cells. Although
terminal boutons of FS and LTS cells were similar in volume, their
synaptic junctional areas differed in size distribution and relation to the dimensions of postsynaptic dendritic shafts or spines. Whereas the
synaptic junctional areas of FS cells (0.024-0.435
µm2; n = 28) sharply and
linearly increased with the circumference of the postsynaptic dendrites
or spines (0.939-5.146 µm), the slope for the junctional area of LTS
cells (0.02-0.103 µm2; n = 29) against circumference (0.844-4.252 µm) was less steep, and a
much weaker correlation was seen. In addition to the differences in
firing patterns, expressed molecules, axonal arborizations, and
postsynaptic targets, this variation in dependency of the synaptic area
on the target size suggests functional differentiation of GABAergic interneurons.
Key words:
neostriatum; interneuron; GABA; parvalbumin; somatostatin; fast spiking cell; low threshold spike; postsynaptic
structure; synaptic junctional area
| |
INTRODUCTION |
GABAergic interneurons are involved
in the formation of response characteristics and rhythmic firing by
regulating neuronal excitability (Sillito, 1992 ; Jefferys et al.,
1996). GABAergic synaptic inputs distribute on several domains along
the neuronal surface, including somata, dendrites, and axons. GABAergic
interneurons are known to be heterogeneous in morphology, physiology,
and chemical composition (Freund and Buzsáki, 1996; Kawaguchi and
Kubota, 1997, 1998; Thomson and Deuchars, 1997; Somogyi et al., 1998). Neuronal surface domains such as somata and dendrites are innervated by
multiple types of GABAergic interneuron, but the functional role of
each remains to be clarified.
In the neostriatum, several types of interneurons with distinct firing
patterns and expression of neuroactive substances are known to exist
(Bolam and Bennet, 1995; Kawaguchi et al., 1995; Kawaguchi, 1997).
Among these subtypes, parvalbumin-containing fast-spiking (FS) cells
exhibiting short-duration action potentials at constant spike
frequency are considered to be GABAergic because they induce
GABAA receptor-mediated inhibition
(Koós and Tepper, 1999), and parvalbumin cells express GABA and
glutamic acid decarboxylase (GAD; an enzyme involved in GABA synthesis)
(Cowan et al., 1990; Kita et al., 1990; Kawaguchi, 1993; Kubota et al.,
1993, Bennett and Bolam, 1994; Augood et al., 1995). In addition,
somatostatin-containing cells exhibiting low-threshold spikes from
hyperpolarized potentials, followed by persistent depolarizations,
[low-threshold spike (LTS) cells] may also be GABAergic because
somatostatin cells were found to be immunoreactive for 67 kDa GAD
(GAD67) when rats are injected with colchicine into the lateral
ventricles or neostriatum (Vuillet et al., 1990; Kubota et al., 1993).
However, GAD mRNAs are not normally detected in somatostatin cells
(Chesselet and Robbins, 1989; Catania et al., 1995), and only a few
somata positive for somatostatin show GABA immunoreactivity (Aoki and
Pickel, 1989; Kubota et al., 1993).
In this study, we found the axon terminals of physiologically
identified LTS cells as well as FS cells to be immunoreactive for GABA.
To reveal the synaptic differences of these two types of GABAergic
interneurons, postsynaptic targets were compared, using
three-dimensional (3-D) reconstruction of electron microscopic images.
Because the postsynaptic junctional area may be related to the size of
the synaptic current (Nusser et al., 1997, 1998; Mackenzie et al.,
1999), its dimensions were measured from the reconstructions, along
with the size of the presynaptic boutons and the postsynaptic targets.
The results indicate that the two types of GABAergic interneurons with
distinct firing patterns and neuroactive substances have different
relationships with postsynaptic elements.
| |
MATERIALS AND METHODS |
Whole-cell recording and intracellular staining
The experiments were performed on young Wistar rats (18-22 d
postnatal). Animals were deeply anesthetized with ether and
decapitated. The brains were quickly removed and submerged in ice-cold
physiological Ringer's solution. Two hundred-micrometer-thick sections
of neostriatum were cut and immersed in a buffered solution (in
mM: NaCl, 124.0; KCl, 3.0; CaCl2,
2.4; MgCl2, 1.2; NaHCO3,
26.0; NaH2PO4, 1.0; and
glucose, 10.0) aerated with a mixture of 95% O2
and 5% CO2.
Neostriatal cells were recorded in a whole-cell mode at 32°C using a
40× water-immersion objective. The electrode solution for the
current-clamp recording consisted of (in mM): potassium methylsulfate 115, KCl 5.0, EGTA 0.5, MgCl2 1.7, ATP 4.0, GTP 0.3, HEPES 8.5, and biocytin 17. Current-clamp recordings
were made in the bridge mode using capacitance neutralization with an
Axoclamp-2B amplifier (Axon Instruments, Foster City, CA). Input
resistances of cells were determined by passing hyperpolarizing current
pulses (duration, 500-600 msec) and inducing voltage shifts of 6-15
mV negative to rest. Spike widths at half amplitude were measured for
spikes elicited by depolarizing current pulses (duration, 50 msec) of
threshold strength. Generation of low-threshold spikes was investigated
by depolarizing current pulses of threshold strength from  75 to 85 mV.
Tissue slices containing biocytin-loaded cells were fixed by immersion
in 4% paraformaldehyde, 2.5% glutaraldehyde, and 0.2% picric acid
overnight at 4°C, and incubated in 0.1 M sodium phosphate buffer (PB) containing 10% sucrose for 1 hr and 20% sucrose for 3 hr,
followed by a freeze-thawing procedure using liquid nitrogen twice. The
slices were then incubated in PB containing 1% sodium borohydrate for
30 min and in 0.05 M Tris-HCl-buffered saline (TBS)
containing 1% H2O2 for 30 min before incubation with avidin-biotin-peroxidase complex in TBS
containing 0.05% Triton X-100 (TX) overnight at 4°C. After washing
in TBS, the slices were reacted with 3,3'-diaminobenzidine tetrahydrochloride (DAB) (0.05%) and
H2O2 (0.003%) in Tris-HCl buffer. They were then post-fixed for 20 min in 0.5%
OsO4 in PB, dehydrated in graded ethanol with 1%
uranyl acetate at the 70% ethanol dehydration state, and flat-embedded
on silicon-coated glass slides in Epon. After reconstruction with a
camera lucida, stained cells were serially sectioned using an ultramicrotome.
Postembedding immunohistochemistry for GABA
Ultrathin sections on nickel mesh grids (200 mesh) were washed
with TBS containing 0.1% TX and incubated with antiserum for GABA
(Sigma, St. Louis, MO; 1:5000) in TBS containing 0.1% TX overnight at
20°C, followed by incubation with colloidal gold (15 nm)-conjugated
anti-rabbit IgG (BioCell; 1:100) overnight at 33°C in TBS containing
0.1% TX (Phend et al., 1992; Buhl et al., 1994) and staining with 1%
uranyl acetate and lead citrate. No immunoreaction was observed in
ultrathin sections incubated in antiserum for GABA that had been
preabsorbed with an excess of bovine serum albumin (BSA)-GABA complex
(0.1 mM). Electron micrographs were taken at 100 kV with a
Hitachi H-7000 electron microscope. Colloidal gold particles were found
commonly in both the mitochondria and cytosol of GABA-positive
terminals. Although they were fewer with than without intracellular DAB
staining, probably because of prevention of the antigen-antibody
interaction by DAB products, the densities of colloidal gold particles
clearly differed between GABA-positive and -negative axons or
dendrites, irrespective of DAB reaction products, as described earlier
for cortical slice preparations (Kawaguchi and Kubota, 1998). In the DAB-stained GABA-positive terminals, there were more particles on
mitochondria without reaction products than in the cytosol filled with
DAB reaction products.
Three-dimensional reconstruction of successive
ultrathin sections
Serial ultrathin (90 nm thickness) sections were mounted on
formvar-coated single-slot (2 × 1 mm) grids. Electron microscopic images of the labeled terminals and associated structures were captured
using a CCD camera (Kodak Megaplus 1.4i) and reconstructed using a 3-D
reconstruction system with the software developed by Noesis
(Vélizy, France) as an extension of their Visilog program.
Double-labeling immunohistochemistry
Two hundred-micrometer-thick slices of rat neostriatum (18-40 d
postnatal) were incubated for 2-3 hr in the above-described oxygenated
extracellular solution. After further incubation for 3 min in an
oxygenated Ca2+-free solution containing
(in mM) 250.0 sucrose, 3.0 KCl, 5.0 MgCl2, 26.0 NaHCO3, and
10.0 glucose to prevent transmitter release from axon terminals, the
slices were immersed in one of the fixatives (4% paraformaldehyde,
2.5% glutaraldehyde, and 0.2% picric acid for fluorescence and 4%
paraformaldehyde, 0.5% glutaraldehyde, and 0.2% picric acid for EM)
and irradiated for 20 sec in a microwave oven. Then they were immersed
in the same fixative overnight at 4°C and incubated in PB containing
10% sucrose for 1 hr and 20% sucrose for 2-3 hr.
Double immunofluorescence. The slices were cut in a
cryostat at 6 µm thickness. Sections were washed in TBS and incubated with a mixture of (1) a rabbit antiserum against parvalbumin (Swant, Bellinzona, Switzerland; diluted 1:2000) and a mouse monoclonal antibody against GABA (Chemicon, Temecula, CA; 1:200), (2) a rabbit antiserum against somatostatin 28 (1-12) (S-320; a gift from Dr. Robert Benoit, Montreal General Hospital; 1:4000) and the GABA antibody, or (3) a rabbit antiserum against dopamine (Incstar, Stillwater, MN; 1:4000) and the GABA antibody in TBS containing 10%
normal goat serum (NGS), 2% BSA, and 0.5% TX overnight. After washing, the sections were incubated with a combination of Texas red-conjugated anti-rabbit IgG (N2034; 1:100; Amersham, Arlington Heights, IL) and dichlorotriaginyl amino fluorescein (DTAF)-conjugated anti-mouse IgG (192F; 1:100; Chemicon) in TBS containing NGS, BSA, and
TX for 3 hr or overnight. The sections were coverslipped in FluoroGuard
(Bio-Rad, Hercules, CA) and observed under a laser confocal microscope
(MRC-1024; Bio-Rad).
Double immunolabeling at the EM level. After freeze-thawing
in liquid nitrogen, neostriatal slices were embedded in a 12% gelatin
solution, fixed, and re-sectioned on a slicer (VT 1000S; Leica,
Nussloch, Germany) at 50 µm thickness (Deuchars et al., 1994).
Sections were washed in TBS and incubated with the rabbit antiserum
against parvalbumin or somatostatin 28 (1-12) in TBS containing 10%
NGS, 2% BSA and 0.04% TX overnight. After washes with TBS, the
sections were incubated with a 1 nm colloidal gold-labeled goat
anti-rabbit IgG (RPN470; 1:50; Amersham) in TBS containing 0.8% BSA,
0.02% gelatin, and 2 mM NaN3
overnight. After silver amplification (silver enhancement kit RPN491;
Amersham), the sections were prepared for electron microscopy as
described above. Ultrathin sections were cut, and GABA postembedding
immunohistochemistry was applied using mouse monoclonal antibody
against GABA (1:100; Chemicon) and then colloidal gold (15 nm)-conjugated anti-mouse IgG (BioCell).
Data given are mean ± SD values. The Mann-Whitney U
test was used for statistical comparisons
| |
RESULTS |
GABA-immunoreactive terminals of neostriatal
interneuron subtypes
The neostriatal interneurons can be divided into several classes
(Kawaguchi, 1993, 1997): (1) FS cells have low input resistances and
hyperpolarized membrane potentials, fire short-duration action potentials at constant spike frequency during depolarizing pulses (Fig.
1A1),
and are immunoreactive for parvalbumin; (2) LTS cells induce LTS from
hyperpolarized potentials, followed by persistent depolarizations (Fig.
1B1) and are positive for
somatostatin and nitric oxide synthase (NOS); (3) large cholinergic
cells show long-lasting afterhyperpolarization after spikes
(long-lasting afterhyperpolarization cells, LA cells).
View larger version (113K):
[in this window]
[in a new window]
|
Figure 1.
Physiological characterization and
GABA-immunoreactive terminals of two neostriatal interneuron types. The
somata and dendrites are shown in black and the axons in
gray. A, FS cells.
A1, An FS cell with
hyperpolarized resting potential (r.p.), which rapidly,
but transiently, fired short-duration spikes with a constant interspike
interval when depolarized with a current pulse. Firing sometimes
resumed during the depolarization.
A2-A4,
Three FS cells used for electron microscopic studies. They have
restricted dendritic fields and axons densely collateralizing in the
dendritic field. A5, An
identified axon terminal of FS cell number 1 making a symmetrical
synapse with a dendritic shaft (large open arrow). The
terminal is immunoreactive for GABA as shown by the presence of 15 nm
colloidal gold particles. Strongly (filled
arrows) and very weakly labeled neural elements (small
open arrows) are apparent beside the FS cell terminal.
B, LTS cells. B1,
An LTS cell with depolarized resting potentials (r.p.) and high input resistances. Two
potential responses are shown superposed for the injected currents
shown in the bottom traces (scales as in
A1). Note that the cell fired a
low-threshold spike after cessation of a hyperpolarization pulse.
B2-B4, Three LTS cells used for
electron microscopic observation. They have less compact dendritic
arborization, often running long distances without branching or
turning. The axons are also diffusely distributed, and the entire
axonal field extends as far as 1000 µm. B5, An
identified axon terminal of LTS cell number 1 making a symmetrical
synapse with a dendritic shaft (open arrow). This
terminal is also immunoreactive for GABA, as shown by the 15 nm
colloidal gold particles. Scale bars:
A2-A4,
B2-B4, 100 µm;
A5, B5, 0.5 µm.
|
|
To identify which interneurons are GABAergic, GABA immunoreactivity in
the axon collaterals of physiologically identified, intracellularly
stained interneurons was investigated by postembedding immunohistochemistry of ultrathin sections using colloidal gold particles (Kawaguchi and Kubota, 1998). The FS cells (n = 3) had resting potentials of 77.3 ± 3.8 (SD) mV, input
resistances of 263 ± 79 M , spike-widths at half
amplitude of 0.39 ± 0.05 msec, cross-sectional somatic areas of
109 ± 14 µm2, and maximal somatic
diameters of 14.0 ± 1.5 µm. The LTS cells (n = 3) had resting potentials of 53.7 ± 2.9 mV, input resistances of 1523 ± 141 M, spike-widths at half amplitude of
1.1 ± 0.4 msec, cross-sectional somatic areas of 123 ± 20 µm2, and maximal somatic diameters of
18.1 ± 2.3 µm. The LA cells (n = 2) had resting
potentials of 57.5 ± 4.9 mV, input resistances of 517 ± 156 M, spike-widths at half amplitude of 0.93 ± 0.04 msec, cross-sectional somatic areas of 352 ± 18 µm2, and maximal somatic diameters of
29.9 ± 3.1 µm. The amount of current necessary to elicit a
spike was greater in FS cells than in LTS cells. FS cells abruptly
started nonadapting repetitive discharges above threshold intensity in
response to depolarizing current pulses, ceased firing abruptly, and
sometimes resumed again after a quiescent period within the period of
the same depolarizing pulse (Fig.
1A1). On the other hand, LTS cells
showed low-threshold spikes elicited from hyperpolarized potentials
(Fig. 1B1). FS cells densely
innervated areas close to the dendritic field (Fig. 1A2-A4),
whereas LTS cells innervated wider areas (Fig.
1B2-B4).
GABA immunoreactivity was investigated at the axonal boutons of the FS,
LTS, and LA cells. All terminals of three FS cells showed gold particle
labeling for GABA (Fig. 1A5). This
was also the case for most axonal boutons of three LTS cells (Fig.
1B5), but the density of colloidal
gold particles on terminals was only approximately half that of FS
cells. Very few or no gold particles were found on axonal boutons and
fibers of two LA cells (data not shown). The densities of colloidal
gold particles for GABA on the boutons were 43.5 ± 20.1 particles/µm2 (range, 7.0-95.4;
n = 44) for an FS cell (FS cell number 1) (see Fig.
3A) and 24.5 ± 10.4 particles/µm2 (range, 8.2-48.8;
n = 32) for an LTS cell (LTS cell number 1) (see Fig.
3A), the difference being significant
(p < 0.0001). Other DAB-free boutons near the
biocytin-loaded DAB-stained ones could be divided into two groups on
the basis of the particle for GABA density: one with the range from 0 to 34.6 particles/µm2 (5.0 ± 5.9;
n = 222) and the other from 61.3 to 420.4 particles/µm2 (209.2 ± 82.2;
n = 121) (see Fig. 3A). We assumed the
former to be non-GABAergic and the latter to be GABAergic. Particles on
the biocytin-loaded DAB-stained boutons of the FS and LTS cells were
significantly more numerous than those on non-GABAergic ones, but
significantly fewer than those on GABAergic ones
(p < 0.0001). These observations indicated the
axonal boutons of FS and LTS cells to be positive for GABA. However,
dense DAB reaction products may prevent the antigen-antibody
interaction in postembedding immunohistochemistry (Kawaguchi and
Kubota, 1998). Very few or no gold particles (4.5 ± 4.3 particles/µm2; range, 0-24.5;
n = 15) were found on the axonal boutons and fibers of
an LA cell (see Fig. 3A), similar to the non-GABA case.
To confirm the existence of multiple types of GABAergic interneurons in
the neostriatum, the coexistence of GABA with parvalbumin or
somatostatin was investigated using immersion-fixed slices. Double
immunofluorescence revealed most of the parvalbumin-positive varicose
fibers and more than half of the somatostatin-positive varicose fibers
to show GABA immunoreactivity (Fig.
2A,B). In contrast,
dopamine-positive fibers were negative (data not shown).
View larger version (152K):
[in this window]
[in a new window]
|
Figure 2.
GABA immunoreactivity of parvalbumin- or
somatostatin-containing fibers in immersion-fixed slices.
A, Laser confocal images of the same section stained by
double immunofluorescence for parvalbumin
(A1) and GABA
(A2). Most parvalbumin-positive
fibers show GABA immunoreactivity (arrowheads).
B, Laser confocal images of the same section for
somatostatin (B1) and GABA
(B2) immunofluorescence. Many
somatostatin-immunoreactive fibers are GABA-positive
(arrowheads). Scale bar, 20 µm. C,
D, Double immunolabeled ultrathin sections. A
parvalbumin-immunoreactive axon terminal (C, large open
arrow) and a somatostatin-immunoreactive axon (D, large
open arrow) labeled with intensified gold particles
(arrows) are immunoreactive for GABA, as indicated by
the 15 nm colloidal gold particles. Neural elements with many colloidal
gold particles (thick filled arrows) and with very few
or no particles (small open arrows) are present. Scale
bar, 0.5 µm.
|
|
At the electron microscopic level, parvalbumin- and
somatostatin-immunoreactive axon terminals labeled with
silver-intensified gold particles demonstrated colloidal gold particles
from the GABA immunoreaction (Fig. 2C,D). The particle
density for GABA on parvalbumin-immunoreactive axonal boutons
(100.5 ± 52.3 particles/µm2;
range, 32.3-227.1; n = 18) was significantly larger
than that on somatostatin-immunoreactive ones (72.9 ± 46.9 particles/µm2; range, 15.5-216.1;
n = 33) (p < 0.05). Other
boutons free of silver-intensified gold particles near the parvalbumin-
or somatostatin-immunoreactive ones could be divided into two groups on
the basis of the particle density for GABA: one with the range from 0 to 27.7 particles/µm2 (3.3 ± 5.5;
n = 72) and the other from 50.4 to 335.6 particles/µm2 (135.6 ± 66.1;
n = 96) (Fig.
3B). The former were assumed
to be non-GABAergic and the latter to be GABAergic. Particles on for
GABA parvalbumin boutons were significantly more numerous than those on
non-GABAergic ones (p < 0.0001) and were not
statistically different from those on GABAergic ones
(p > 0.05), indicating parvalbumin axons to be
positive for GABA. Particles for GABA on somatostatin boutons were
significantly more numerous than on GABA-negative
(p < 0.0001), but significantly fewer than on GABA-positive ones (p < 0.0001). These results
indicate that somatostatin boutons express GABA with lower content than
their parvalbumin counterparts.
View larger version (31K):
[in this window]
[in a new window]
|
Figure 3.
Densities of colloidal gold particles on
postembedding GABA immunoreactions at the axonal boutons of interneuron
types. A, The distributions of particle density for GABA at
the FS, LTS, and LA cell boutons identified physiologically and stained
with DAB. Control boutons not stained intracellularly and free of DAB
reaction products could be divided into two groups with the densities
for GABA from 0 to 34.6 particles/µm2 and from
61.3 to 420.4 particles/µm2. The former were
assumed to be non-GABAergic and the latter to be GABAergic.
B, The distributions of particle densities for GABA at
parvalbumin (PV)- and somatostatin
(SOM)-containing boutons identified with
silver-intensified gold particles at pre-embedding
immunohistochemistry. Control boutons not stained by pre-embedding
immunohistochemistry and free of silver-intensified gold particles
could be divided into two groups with densities for GABA from 0 to 27.7 particles/µm2 and from 50.4 to 335.6 particles/µm2. Arrows indicate mean
values for non-GABAergic (non-GABA mean) and GABAergic
(GABA mean) boutons and for boutons of each cell type
(mean).
|
|
Postsynaptic targets and synaptic structures of axon terminals of
FS and LTS cells
To assess the differences in synaptic connections between these
two GABAergic interneuron types, postsynaptic targets and synaptic
structures made by their axon terminals were compared. For this
purpose, 38 terminal boutons of three FS cells and 28 terminal boutons
of three LTS cells were reconstructed three-dimensionally from serial
ultrathin sections (Fig. 4, Table
1). Synaptic junctions made by labeled
terminals were identified using the following criteria (Buhl et al.,
1995): (1) tight apposition of presynaptic and postsynaptic membrane
profiles with a widening of the extracellular space and a dense or
intermediate plaque of intercellular materials; (2) accumulation of
synaptic vesicles in the presynaptic terminal; and (3) postsynaptic
density. Small synaptic junctions such as those on spine stalks and
thin dendritic shafts (0.3-0.5 µm in diameter) were sometimes
difficult to identify because they appeared only in a few ultrathin
sections. Identification of synaptic junctions on tiny postsynaptic
targets sectioned obliquely was more difficult even though the
specimens were tilted to an appropriate angle for observation of
synaptic clefts. Therefore, small synaptic junctions were missed more
frequently than larger ones.
View larger version (138K):
[in this window]
[in a new window]
|
Figure 4.
Three-dimensional analysis of terminals of FS
(A-C) and LTS (D-F) cells. In
B1, C1,
C2, D1,
D2, and E1, two images
are shown for stereoscopic observation. A1, 3-D
reconstruction images of a terminal of FS cell number 1 and associated
structures are rotated ~25° each from left to right. An
intracellularly labeled axon terminal of the FS cell (red)
makes a symmetrical synapse on a postsynaptic spiny dendrite
(green). Two of the spine heads receive asymmetrical
synapses (blue and dark blue). The other terminal
(pink) makes a symmetrical contact on the other side
of the dendrite. A2, The same
dendrite as in A1 is rotated in the same
way except that synaptic junctions are indicated by the same colors as
the terminal boutons in A1. The synaptic
junctional area of the FS cell terminal (red) was 0.298 µm2. B1, Two
successive axonal boutons of FS cell number 1 make synaptic junctions
0.8 µm apart on the same proximal dendrite 2 µm distant from the
soma. Two synaptic junctions are shown in
B2 at the same magnification as in
A. The synaptic junctional areas of the FS cell terminals
were 0.19 (left) and 0.18 µm2
(right), respectively.
C1, Another axon terminal
(red) of FS cell number 1 makes a symmetrical synaptic
contact on a spine neck. The spine receives an asymmetrical terminal on
the head (dark blue) and another spine also an asymmetrical
terminal (blue). Another terminal (orange) makes
a symmetrical synapse on the dendritic shaft.
C2, The same dendrite as in
C1 except that synaptic junctions are
indicated by the same colors as the terminal boutons in
C1. The synaptic junctional area of the FS
cell terminal (red) was 0.04 µm2.
D1, A terminal of LTS cell number 1 (red) makes a symmetrical synaptic contact on a shaft of a
spiny dendrite (green).
D2, The synaptic junctional area
(0.088 µm2) is indicated by red.
E1, A terminal of LTS cell number 2 (red) makes a symmetrical synaptic junction on a trunk of a
spiny dendrite (green). Two spines nearby receive
asymmetrical synaptic terminals on the head (blue).
E2, The synaptic junctional area
(0.068 µm2) is indicated by red.
F1, A terminal of LTS cell number 1 and associated structures are rotated ~30° from left to right. The
terminal (red) makes a symmetrical synaptic contact on a
spine stalk. The spine head receives an asymmetrical terminal
(dark blue) and other three spines, also asymmetrical
terminals (blue), on the head.
F2, The same dendrite as in
F1 is rotated in the same way, except that
synaptic junctions are indicated by the same colors as the terminal
boutons in F1. The synaptic junctional
area of the terminal (red) was 0.068 µm2. Scale bars: A,
B2, C-F, 0.5 µm;
B1, 0.8 µm.
|
|
Reconstructed synaptic terminals showed bouton-like swellings. Most
terminal boutons made one synaptic junction except three (one for an FS
cell and the other two for LTS cells), making two synaptic junctions on
different postsynaptic dendrites. The synaptic terminals of FS cells
were of symmetrical type and made 11 contacts on somata and 28 on
dendrites (Table 1; Figs. 4A-C,
5A,B). Seventeen postsynaptic
dendrites of FS cell terminals were identified as spiny from the
reconstructed morphology (Fig. 4A,C). Two terminals of FS cells innervated dendritic spines (Table 1). One of them made a
synapse onto the stalk of a spine with an asymmetrical synapse on the
head (Figs. 4C, 5B). The other was on the head of
a thin spine with an asymmetrical synapse on the opposite side of the
head. Four terminals of FS cells made synapses on thick aspiny
dendrites ~5 µm in circumference (Fig. 4B), and
one terminal impinged on a thin aspiny dendrite ~2 µm in
circumference. It was not possible to determine whether the remaining
six dendrites innervated by FS cell terminals were spiny or aspiny,
because the tissue structures were not well preserved. Nine somata
innervated by FS cells had nuclei without folding, another had an
indented nucleus. It could not be determined whether the remaining one soma had an indented nucleus or not.
View larger version (207K):
[in this window]
[in a new window]
|
Figure 5.
Electron micrographs showing symmetrical synapses
of axon terminals used for 3-D reconstructions. A,
B, The symmetrical synapses in Figure 4, A and
C (FS cell number 1), on the dendritic shaft (open
arrow) and on the spine neck (open arrow),
respectively. B, Filled arrow, An asymmetrical synapse
on the spine head. C, D, The symmetrical
synapses in Figure 4, D and F (LTS cell
number 1), on the dendritic shaft (open arrow) and on
the spine neck (open arrow), respectively. D,
Filled arrow, An asymmetrical synapse on the spine head.
D, Double arrows, A spine apparatus. Scale bar, 0.5 µm.
|
|
The synaptic terminals of LTS cells (n = 30) made most
synapses onto dendrites except for one case on the soma (Table 1; Figs.
4D-F, 5C,D). Twelve postsynaptic
dendrites of LTS cell terminals were identified as spiny (Table 1, Fig.
4D-F). Two terminals made synapses onto a
spine stalk with an asymmetrical synapse on the heads (Figs.
4F, 5D). One terminal innervated a large
aspiny dendrite ~4 µm in circumference. We could not identify
whether the remaining 16 dendrites were spiny or not. One LTS terminal was found to innervate a soma without nuclear indentation (Table 1).
The LTS cells had fewer synaptic contacts on somata than the FS cells.
The volume and synaptic junctional areas of the terminal boutons of FS
and LTS cells were measured from the 3-D reconstructions. The synaptic
junctional areas of FS cell terminals were larger on average and more
variable in distribution than those of LTS cell terminals (Table
2, Fig.
6A1,B1).
The synaptic junctional areas of FS cell terminals on somata were
larger on average than those on dendrites (Table 2). Significant
differences were found between the synaptic junctional areas of
axodendritic and axosomatic terminals of FS cells
(p < 0.005), axodendritic terminals of FS and
LTS cells (p < 0.0001), and axosomatic
terminals of FS cells and axodendritic terminals of LTS cells
(p < 0.0001) (Table 2). The range of bouton
sizes was about the same for the FS and LTS cells, and no significant
difference was found (Table 2). No correlation was found between the
volume of presynaptic boutons and area of synaptic junctions in FS and
LTS cells (Fig.
6A2,B2).
View larger version (34K):
[in this window]
[in a new window]
|
Figure 6.
Synaptic junction areas and volumes for terminal
boutons of FS cells (A) and LTS cells
(B). A1,
B1, Distributions of synaptic junction
areas of FS and LTS cell terminals. The junctional areas of synapses
onto dendrites of FS cells are more variable than for LTS cells, with
values of 0.024-0.435 µm2, as opposed to <0.103
µm2. Similar size variation was seen for the
junctional areas onto somata of FS (0.044-0.514
µm2), but a larger junctional area (0.361 µm2) was found for a somatic synapse of the LTS
cell. Synapses on somata are shown in black, and on
dendrites in gray. A2,
B2, Relationship between synaptic
junction area and terminal bouton volume (gray
circles on dendrites; black triangles on somata)
for FS and LTS cells. The bouton volumes of FS and LTS cell terminals
are distributed similarly. No correlation was found between bouton
volume and junctional area.
|
|
The circumference of the postsynaptic dendrites or spines was also
measured. The ranges for those innervated by FS and LTS cells were
similar with no significant difference (Table 2). The synaptic
junctional areas of FS cells (0.024-0.435
µm2; n = 28) sharply and
linearly increased with the circumference of the postsynaptic dendrites
or spines (0.939-5.146 µm) (Fig. 7A1,B1).
The increase of the junctional area of LTS cells (0.02-0.103 µm2; n = 29) with the
circumference (0.844-4.252 µm) was less steep (Fig.
7A2,B2), and the
synaptic area was always <0.103 µm2.
The correlation coefficients for total synapses of three FS cells and
for those of three LTS cells were 0.98 and 0.38, respectively. The
regression line slopes (regression coefficients) were 0.09 µm for
total synapses of three FS cells
(r2 = 0.95; p < 0.0001; ANOVA test) and 0.01 µm for those of three LTS cells
(r2 = 0.14; p = 0.0423).
View larger version (27K):
[in this window]
[in a new window]
|
Figure 7.
A, Relationship of the synaptic
junction area to target structure circumference for three FS and three
LTS cells. The data were obtained from the 3-D reconstructions of
serial ultrathin sections. Synapses on dendritic shafts are represented
by filled symbols and on spine necks by open
symbols. Each solid line is a simple regression
fit to a set of data. A1, The
data point indicated by the curved arrow (red) is the
sum of two synapses from the same FS cell 0.8 µm apart on the same
target dendrite (shown in Fig. 4B). Correlation
coefficients and slopes (regression coefficients) for the regression
lines were: FS cell number 1 (n = 13; red
circles), 0.97 and 0.084 µm (p < 0.0001; ANOVA test); FS cell number 2 (n = 5;
blue triangles), 0.99 and 0.087 µm
(p = 0.0005); FS cell number 3 (n = 9; green squares), 0.99 and
0.095 µm (p < 0.0001).
A2, Regression fits for the LTS
cells showed a much less steep slope than for the FS cells and a
greater spread in the data. Correlation coefficients and slopes for
these cells were: LTS cell number 1 (n = 9;
pink diamonds), 0.49 and 0.014 µm
(p = 0.1818); LTS cell number 2 (n = 12; brown inverted triangles),
0.75 and 0.022 µm (p = 0.0047); LTS cell
number 3 (n = 8; blue circles), 0.58 and 0.009 µm (p = 0.1304).
B, 3-D reconstruction images of postsynaptic dendrites
(green) of FS (B1)
and LTS cells (B2). The area of the
synaptic junctions (red) of the FS cells clearly
increased with the size of the postsynaptic structures, whereas those
of the LTS cells did not increase sharply. Scale bar, 0.5 µm.
|
|
These observations suggest that the dependence of synaptic
junctional area on the circumference of the postsynaptic dendrite differs between neostriatal GABAergic interneuron types (Fig. 8).
View larger version (49K):
[in this window]
[in a new window]
|
Figure 8.
Schematic view of synaptic connections of
GABAergic FS and LTS cells of the rat neostriatum. In FS cells, the
synaptic junctional area (red regions in the terminal
boutons) sharply and linearly increases with the circumference of the
postsynaptic dendrite or spine. Those of the LTS cells
(blue regions in the terminal boutons) demonstrate a
less pronounced increment in size. NO, Nitric oxide;
PV, parvalbumin; SOM, somatostatin.
|
|
| |
DISCUSSION |
The major findings of the present study can be summarized as
follows (Fig. 8): (1) the axon terminals of both parvalbumin FS cells
and somatostatin LTS cells are immunoreactive for GABA in
immersion-fixed slices, and the GABA content at the axonal boutons of
parvalbumin FS cells may be larger than that of somatostatin LTS cells;
(2) FS cells make a greater proportion of synaptic contacts onto somata
than LTS cells; (3) although terminal boutons of FS and LTS cells are
similar in volume, their synaptic junctional areas differ in size
distribution and relation to dimensions of postsynaptic dendritic
shafts or spines; and (4) the junctional area of FS cells sharply and
linearly increases with the circumference of the postsynaptic dendrites
or spines, whereas the increment with LTS cells is less pronounced.
Heterogeneity of neostriatal GABAergic interneurons
GABA immunoreactivity was detected in the axon terminals of
parvalbumin FS and somatostatin LTS cells by three different
immunohistochemical stainings using neostriatal slice
preparations. In perfusion-fixed tissues, most
parvalbumin-immunoreactive fibers were intensely stained with GABA
by double immunofluorescence, whereas only a few
somatostatin-immunoreactive fibers were stained with GABA (our unpublished observations). We adopted
immersion-fixed slices because GABA in the cytoplasm might be better
and more rapidly fixed with immediate glutaraldehyde immersion and
microwave irradiation than with glutaraldehyde perfusion. Similarly,
immunoreactivity of aspartate in nerve terminals is much stronger in
slices than in sections of perfusion-fixed brains (Gundersen et al.,
1998). Hypoglycemia treatment before perfusion also increases aspartate immunoreactivity, suggesting that low neuronal activity in in vitro slices and hypoglycemic animals may increase the content of
aspartate or GABA in axon terminals (Gundersen et al., 1998). In our
immersion-fixed slices, GABA immunoreactivity was found in the
terminals of FS and LTS cells, but not LA cells. Similarly, the fibers
and boutons positive for parvalbumin and somatostatin were
immunoreactive for GABA, but those for dopamine were not. These
observations are in line with localization of GABA as a transmitter at
the axon terminals.
GABA contents at the terminal boutons, from the observed density of
particles, significantly differed between the two types of GABAergic
interneurons. The particle density for FS cell boutons was 1.8 times
larger than that of LTS cell ones identified with intracellular
staining, and that for parvalbumin boutons 1.4 times larger than that
for somatostatin ones identified with pre-embedding immunohistochemistry. These observations suggest that GABA content at
the axonal boutons may vary among GABAergic interneuron types.
Specialization of synaptic terminal structures for
interneuron subtypes
Because the postsynaptic targets of FS and LTS cells include spiny
dendrites and somata without nuclear invagination, both may innervate
spiny projection cells (Dimova et al., 1980). FS cells may also
innervate aspiny interneurons because one FS terminal was observed to
make a synapse onto the soma with nuclear invagination.
Although synaptic contacts onto somata were more common with FS than
with LTS cells, the synaptic localization on dendrites appeared similar
for the two types. Four axospinous terminals, two from FS cells and two
from LTS cells, were found to make symmetrical synapses onto the stalk
or head with an asymmetrical synapse on the head. This spatial
arrangement of synapses on the spine would be efficient to suppress
transmission of excitatory potential from the head to the shaft. In
addition, many synapses of FS and LTS cells on shafts of spiny
dendrites were located close to the base of the spines. Inhibitory
terminals on shafts could also be associated with the regulation of
excitatory inputs onto spines as well as distal parts of dendrites.
Although the terminal boutons of FS and LTS cells were similar in
volume distribution, the range of the synaptic junction area of these
two types was very different. The variability of junctional areas of FS
cells seemed to be attributable to adaptation to the size of the
postsynaptic dendrites. Although only three FS cells were analyzed, all
showed the same relationship. Dependence of junctional areas on
postsynaptic dimensions has also previously been observed at
asymmetrical (probably excitatory) synapses onto spines. The
asymmetrical synaptic specialization increases in area with the spine
head volume or surface area of neostriatal spiny projection cells,
cerebellar Purkinje cells, and hippocampal pyramidal cells (Wilson et
al., 1983; Harris and Stevens, 1988, 1989).
Recently, using a combined physiological and anatomical approach,
Nusser et al. (1997) demonstrated that the distribution in quantal
amplitudes of IPSCs parallel that of synaptic
GABAA receptor number and synapse area in
cerebellar stellate neurons. Potentiation of inhibitory currents after
kindling is accompanied by increase in the number of
GABAA receptors and the synaptic junctional area
(Nusser et al., 1998). A direct demonstration that synapse size is
positively correlated with the amplitude of the postsynaptic current
was recently provided by Mackenzie et al. (1999). Using calcium
imaging, whole-cell recording, and electron microscopic examination of
the same synapse, the amplitudes of NMDA receptor-mediated EPSCs in
cultured cortical neurons was shown to be positively correlated to
synaptic size. These results suggest that the synaptic junctional area
could be used as a measure of relative receptor content and
postsynaptic currents. GABAergic currents induced by FS cells may be
larger at thicker dendrites, and a single FS cell could induce
inhibitory postsynaptic currents of different amplitudes, depending on
the postsynaptic dendritic size.
Voltage-gated ion channels are known to be distributed not only on
somata but also on dendrites (Yuste and Tank, 1996; Magee, 1998; Magee
et al., 1998; Stuart and Spruston, 1998). With a subthreshold potential, however, passive cable properties as well as
voltage-dependent resting conductances are important determinants of
amplitude of postsynaptic potentials. Because the circumference of the
postsynaptic target is related to the input resistance (Rall, 1995) and
the synaptic junctional area to the number of receptors (Nusser et al.,
1997), change of junctional areas according to postsynaptic dimension
may be attributable to adjustment of GABAergic currents. The dependence
of synaptic areas of FS cell terminals on postsynaptic dendritic
circumference may maintain the ratio of synaptic conductance and input
resistance constant. Convergence of terminals from a single GABAergic
interneuron on the same postsynaptic cell was not investigated in this
study. However, we found two synapses of FS cell number1 0.8 µm apart
on the same dendrite close to the soma (4.91 µm in circumference, 2 µm distant from the soma) (Figs. 4B,
7A1, curved arrow). The total
synaptic area of these two synapses fit on the regression line of FS
cells well, suggesting that FS cells may adjust the synaptic area to
postsynaptic size by making multiple synapses on the target in some cases.
The contrasting weak correlation between synaptic junctional area and
postsynaptic size seen in the LTS case might have been influenced by
the fact that only three cells were analyzed. However, the junctional
areas were always <0.103 µm2, which
suggests the relative constancy, so that similar postsynaptic currents
may be induced in LTS cells irrespective of the synaptic location. From
the axon terminals of LTS cells, several transmitters such as
somatostatin, neuropeptide Y, NO, and GABA are thought to be released.
Some of them may not use ionotropic receptors limited to postsynaptic
junctional areas, but also G-protein-coupled receptors or extrasynaptic
receptors whose effects on the target are not related to the junctional area.
Neostriatal FS cells are known to have dense innervations close to the
dendritic field and express parvalbumin, whereas LTS cells have
widespread innervations and express somatostatin, neuropeptide Y, and
NOS. The terminals of FS cells make more synaptic contacts on
somata than those of LTS cells. In addition to the differences in
firing patterns, axonal arborizations, expressed molecules, and
postsynaptic targets, the presently demonstrated variation in
dependence of synaptic area on the target size suggests functional differentiation of GABAergic interneurons.
| |
FOOTNOTES |
Received March 8, 1999; revised Oct. 11, 1999; accepted Oct. 11, 1999.
This work was supported by Grants-in-Aid for Scientific Research from
the Japanese Ministry of Education, Science, Sports and Culture, and
the Frontier Research Program RIKEN. We thank Dr. R. Kado for
discussions, Drs. C. J. Wilson, B. Bennett, and T. K. Hensch
for comments, Dr. E. L. White for suggestions on the
three-dimensional reconstruction analysis program, Dr. A. M. Thomson for advice on the histological procedure, and Ms. N. Wada and
S. Kato for technical assistance. We are grateful to Dr. R. Benoit for
the gift of antiserum against somatostatin.
Correspondence should be addressed to Yasuo Kawaguchi, Laboratory of
Cerebral Circuitry, National Institute for Physiological Sciences,
Myodaiji, Okazaki 444-8585, Japan. E-mail: yasuo{at}nips.ac.jp.
| |
REFERENCES |
-
Aoki C,
Pickel V
(1989)
Neuropeptide Y in the cerebral cortex and the caudate-putamen nuclei: ultrastructural basis for interactions with GABAergic and non-GABAergic neurons.
J Neurosci
9:4333-4354[Abstract].
-
Augood S,
Herbison A,
Emson P
(1995)
Localization of GAT-1 GABA transporter mRNA in rat striatum: cellular coexpression with GAD67 mRNA, GAD67 immunoreactivity, and parvalbumin mRNA.
J Neurosci
15:885-874.
-
Bennett BD,
Bolam JP
(1994)
Synaptic input and output of parvalbumin-immunoreactive neurons in the neostriatum of the rat.
Neuroscience
62:707-719[Web of Science][Medline].
-
Bolam JP,
Bennet BD
(1995)
Microcircuitry of the neostriatum.
In: Molecular and cellular mechanism of neostriatal function (Arino M,
Surmeier D,
eds), pp 1-19. Austin: R.G. Landes.
-
Buhl E,
Halasy K,
Somogyi P
(1994)
Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites.
Nature
368:823-828[Medline].
-
Buhl E,
Cobb S,
Halasy K,
Somogyi P
(1995)
Properties of unitary IPSPs evoked by anatomically identified basket cells in the rat hippocampus.
Eur J Neurosci
7:1989-2004[Web of Science][Medline].
-
Catania M,
Tölle T,
Monyer H
(1995)
Differential expression of AMPA receptor subunits in NOS-positive neurons of cortex, striatum, and hippocampus.
J Neurosci
15:7046-7061[Abstract].
-
Chesselet M,
Robbins E
(1989)
Characterization of striatal neurons expressing high levels of glutamic acid decarboxylase messenger RNA.
Brain Res
492:237-244[Web of Science][Medline].
-
Cowan R,
Wilson CJ,
Emson P,
Heizmann C
(1990)
Parvalbumin-containing GABAergic interneurons in the rat neostriatum.
J Comp Neurol
302:197-205[Web of Science][Medline].
-
Deuchars J,
West DC,
Thomson AM
(1994)
Relationships between morphology and physiology of pyramid-pyramid single axon connections in rat neocortex in vitro.
J Physiol (Lond)
478:423-435[Abstract/Free Full Text].
-
Dimova R,
Vuillet J,
Seite R
(1980)
Study of the rat neostriatum using a combined Golgi-electron microscope technique and serial sections.
Neuroscience
5:1581-1596[Web of Science][Medline].
-
Freund TF,
Buszáki G
(1996)
Interneurons of the hippocampus.
Hippocampus
6:347-470[Web of Science][Medline].
-
Gundersen V,
Chaudhry F,
Bjaalie J,
Fonnum F,
Ottersen O,
Storm-Mathisen J
(1998)
Synaptic vesicular localization and exocytosis of L-aspartate in excitatory nerve terminals: a quantitative immunogold analysis in rat hippocampus.
J Neurosci
18:6059-6070[Abstract/Free Full Text].
-
Harris K,
Stevens J
(1988)
Dendritic spines of rat cerebellar Purkinje cells: serial electron microscopy with reference to their biophysical characteristics.
J Neurosci
8:4455-4469[Abstract].
-
Harris K,
Stevens J
(1989)
Dendritic spines of CA1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics.
J Neurosci
9:2982-2997[Abstract].
-
Jefferys JGR,
Whittington MA,
Traub RD
(1996)
Neuronal networks for induced "40 Hz" rhythms.
Trends Neurosci
19:202-208[Web of Science][Medline].
-
Kawaguchi Y
(1993)
Physiological, morphological and histochemical characterization of three classes of interneurons in rat neostriatum.
J Neurosci
13:4908-4923[Abstract].
-
Kawaguchi Y
(1997)
Neostriatal cell subtypes and their functional roles.
Neurosci Res
27:1-8[Web of Science][Medline].
-
Kawaguchi Y,
Kubota Y
(1997)
GABAergic cell subtypes and their synaptic connections in rat frontal cortex.
Cereb Cortex
7:476-486[Abstract/Free Full Text].
-
Kawaguchi Y,
Kubota Y
(1998)
Neurochemical features and synaptic connections of large physiologically-identified GABAergic cells in the rat frontal cortex.
Neuroscience
85:677-701[Web of Science][Medline].
-
Kawaguchi Y,
Wilson C,
Augood S,
Emson P
(1995)
Striatal interneurons: chemical, physiological and morphological characterization.
Trends Neurosci
18:527-535[Web of Science][Medline].
-
Kita H,
Kosaka T,
Heizmann CW
(1990)
Parvalbumin-immunoreactive neurons in the rat neostriatum: a light and electron microscopic study.
Brain Res
536:1-15[Web of Science][Medline].
-
Koós T,
Tepper JM
(1999)
Inhibitory control of neostriatal projection neurons by GABAergic interneurons.
Nature Neurosci
2:467-472[Web of Science][Medline].
-
Kubota Y,
Mikawa S,
Kawaguchi Y
(1993)
Neostriatal GABAergic interneurons contain NOS, calretinin or parvalbumin.
NeuroReport
5:205-208[Web of Science][Medline].
-
Mackenzie PJ,
Kenner GS,
Prange O,
Shayan H,
Umemiya M,
Murphy TH
(1999)
Ultrastructural correlates of quantal synaptic function at single CNS synapses.
J Neurosci
19:RC13 (1-7).
-
Magee JC
(1998)
Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons.
J Neurosci
18:7613-7624[Abstract/Free Full Text].
-
Magee J,
Hoffman D,
Colbert C,
Johnston D
(1998)
Electrical and calcium signaling in dendrites of hippocampal pyramidal neurons.
Annu Rev Physiol
60:327-346[Web of Science][Medline].
-
Nusser Z,
Cull Candy S,
Farrant M
(1997)
Differences in synaptic GABAA receptor number underlie variation in GABA mini amplitude.
Neuron
19:697-709[Web of Science][Medline].
-
Nusser Z,
Hájos N,
Somogyi P,
Mody I
(1998)
Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses.
Nature
395:172-177[Medline].
-
Phend K,
Weinberg R,
Rustioni A
(1992)
Techniques to optimize post-embedding single and double staining for amino acid neurotransmitters.
J Histochem Cytochem
40:1011-1020[Abstract].
-
Rall W
(1995)
In: The theoretical foundation of dendritic function (Segev I, Rinzel J, Shepherd GM, eds). Cambridge, MA: MIT.
-
Sillito AM
(1992)
GABA-mediated inhibitory processes in the function of the geniculo-striate system.
In: Progress in brain research, Vol 90, GABA in the retina and central visual system (Mize RR,
Marc RE,
Sillito AM,
eds), pp 349-384. Amsterdam: Elsevier.
-
Somogyi P,
Tamás R,
Lujan R,
Buhl E
(1998)
Salient features of synaptic organisation in the cerebral cortex.
Brain Res Rev
26:113-135[Medline].
-
Stuart G,
Spruston N
(1998)
Determinants of voltage attenuation in neocortical pyramidal neuron dendrites.
J Neurosci
18:13501-3510.
-
Thomson AM,
Deuchars J
(1997)
Synaptic interactions in neocortical local circuits: dual intracellular recordings in vitro.
Cereb Cortex
7:510-522[Abstract/Free Full Text].
-
Vuillet J,
Kerkerian-Le Goff L,
Kachidian P,
Dusticier G,
Bosler O,
Nieoullon A
(1990)
Striatal NPY-containing neurons receive GABAergic afferents and may also contain GABA: an electron microscopic study in the rat.
Eur J Neurosci
2:672-681[Web of Science][Medline].
-
Wilson CJ,
Groves P,
Kitai ST,
Linder J
(1983)
Three-dimensional structure of dendritic spines in the rat neostriatum.
J Neurosci
3:383-388[Abstract].
-
Yuste R,
Tank DW
(1996)
Dendritic integration in mammalian neurons, a century after Cajal.
Neuron
16:701-716[Web of Science][Medline].
Copyright © 2000 Society for Neuroscience 0270-6474/0/201375-12$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. G. Partridge, M. J. Janssen, D. Y. T. Chou, K. Abe, Z. Zukowska, and S. Vicini
Excitatory and Inhibitory Synapses in Neuropeptide Y-Expressing Striatal Interneurons
J Neurophysiol,
November 1, 2009;
102(5):
3038 - 3045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Dehorter, C. Guigoni, C. Lopez, J. Hirsch, A. Eusebio, Y. Ben-Ari, and C. Hammond
Dopamine-Deprived Striatal GABAergic Interneurons Burst and Generate Repetitive Gigantic IPSCs in Medium Spiny Neurons
J. Neurosci.,
June 17, 2009;
29(24):
7776 - 7787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. O. Tan and D. Bullock
A Dopamine-Acetylcholine Cascade: Simulating Learned and Lesion-Induced Behavior of Striatal Cholinergic Interneurons
J Neurophysiol,
October 1, 2008;
100(4):
2409 - 2421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Sullivan, H. Chen, and H. Morikawa
Recurrent Inhibitory Network among Striatal Cholinergic Interneurons
J. Neurosci.,
August 27, 2008;
28(35):
8682 - 8690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Bodor, K. Giber, Z. Rovo, I. Ulbert, and L. Acsady
Structural Correlates of Efficient GABAergic Transmission in the Basal Ganglia-Thalamus Pathway
J. Neurosci.,
March 19, 2008;
28(12):
3090 - 3102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Liu, Y. Otsu, C. Vasuta, H. Nawa, and T. H. Murphy
Action-Potential-Independent GABAergic Tone Mediated by Nicotinic Stimulation of Immature Striatal Miniature Synaptic Transmission
J Neurophysiol,
August 1, 2007;
98(2):
581 - 593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Kato, Y. Kawasaki, R.-R. Ji, and A. M. Strassman
Differential wiring of local excitatory and inhibitory synaptic inputs to islet cells in rat spinal lamina II demonstrated by laser scanning photostimulation
J. Physiol.,
May 1, 2007;
580(3):
815 - 833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Uchigashima, M. Narushima, M. Fukaya, I. Katona, M. Kano, and M. Watanabe
Subcellular Arrangement of Molecules for 2-Arachidonoyl-Glycerol-Mediated Retrograde Signaling and Its Physiological Contribution to Synaptic Modulation in the Striatum
J. Neurosci.,
April 4, 2007;
27(14):
3663 - 3676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Narushima, M. Uchigashima, M. Fukaya, M. Matsui, T. Manabe, K. Hashimoto, M. Watanabe, and M. Kano
Tonic Enhancement of Endocannabinoid-Mediated Retrograde Suppression of Inhibition by Cholinergic Interneuron Activity in the Striatum
J. Neurosci.,
January 17, 2007;
27(3):
496 - 506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Xiang, H.-X. Chen, X.-X. Yu, M. A. King, and S. N. Roper
Reduced Excitatory Drive in Interneurons in an Animal Model of Cortical Dysplasia
J Neurophysiol,
August 1, 2006;
96(2):
569 - 578.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Gustafson, E. Gireesh-Dharmaraj, U. Czubayko, K. T. Blackwell, and D. Plenz
A Comparative Voltage and Current-Clamp Analysis of Feedback and Feedforward Synaptic Transmission in the Striatal Microcircuit In Vitro
J Neurophysiol,
February 1, 2006;
95(2):
737 - 752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Kotaleski, D. Plenz, and K. T. Blackwell
Using Potassium Currents to Solve Signal-to-Noise Problems in Inhibitory Feedforward Networks of the Striatum
J Neurophysiol,
January 1, 2006;
95(1):
331 - 341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bracci, D. Centonze, G. Bernardi, and P. Calabresi
Engagement of Rat Striatal Neurons by Cortical Epileptiform Activity Investigated With Paired Recordings
J Neurophysiol,
November 1, 2004;
92(5):
2725 - 2737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Karube, Y. Kubota, and Y. Kawaguchi
Axon Branching and Synaptic Bouton Phenotypes in GABAergic Nonpyramidal Cell Subtypes
J. Neurosci.,
March 24, 2004;
24(12):
2853 - 2865.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Sano, Y. Yasoshima, N. Matsushita, T. Kaneko, K. Kohno, I. Pastan, and K. Kobayashi
Conditional Ablation of Striatal Neuronal Types Containing Dopamine D2 Receptor Disturbs Coordination of Basal Ganglia Function
J. Neurosci.,
October 8, 2003;
23(27):
9078 - 9088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Guzman, A. Hernandez, E. Galarraga, D. Tapia, A. Laville, R. Vergara, J. Aceves, and J. Bargas
Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum
J. Neurosci.,
October 1, 2003;
23(26):
8931 - 8940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bracci, D. Centonze, G. Bernardi, and P. Calabresi
Voltage-dependent membrane potential oscillations of rat striatal fast-spiking interneurons
J. Physiol.,
May 15, 2003;
549(1):
121 - 130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. DeFelipe, J.I. Arellano, A. Merchan-Perez, M.C. Gonzalez-Albo, K. Walton, and R. Llinas
Spaceflight Induces Changes in the Synaptic Circuitry of the Postnatal Developing Neocortex
Cereb Cortex,
August 1, 2002;
12(8):
883 - 891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q.-Q. Sun, J. R. Huguenard, and D. A. Prince
Somatostatin Inhibits Thalamic Network Oscillations In Vitro: Actions on the GABAergic Neurons of the Reticular Nucleus
J. Neurosci.,
July 1, 2002;
22(13):
5374 - 5386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Farries and D. J. Perkel
A Telencephalic Nucleus Essential for Song Learning Contains Neurons with Physiological Characteristics of Both Striatum and Globus Pallidus
J. Neurosci.,
May 1, 2002;
22(9):
3776 - 3787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
