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 Previous Article
The Journal of Neuroscience, July 1, 1998, 18(13):5095-5102
Electrophysiology of the Hippocampal and Amygdaloid Projections
to the Nucleus Accumbens of the Rat: Convergence, Segregation, and
Interaction of Inputs
Antonius B.
Mulder,
Martijn
Gijsberti
Hodenpijl, and
Fernando H.
Lopes da
Silva
Graduate School for Neurosciences, Institute of Neurobiology,
Faculty of Biology, University of Amsterdam, 1098 SM Amsterdam, The
Netherlands
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ABSTRACT |
The nucleus accumbens (Nacb) receives inputs from hippocampus and
amygdala but it is still unclear how these inputs are functionally organized and may interact. The interplay between these input pathways
was examined using electrophysiological tools in the rat, in
vivo, under halothane anesthesia. After fornix/fimbria stimulation (Fo/Fi, subicular projection fibers to the Nacb), mono- and
polysynaptically driven single units were recorded in the medial
shell/core regions of the Nacb and in the ventromedial caudate putamen.
Monosynaptically driven neurons by basolateral amygdala (BLA)
stimulation were found in the medial shell/core and in the
ventrolateral shell/core regions. In the areas of convergence (medial
shell/core), paired activation of BLA followed by that of Fo/Fi
resulted in an enhancement of the Fo/Fi response, whereas stimulation
in the reverse order, Fo/Fi followed by BLA, led to a depression of the
BLA response. In addition to these patterns of interactions, the
tetanization of the Fo/Fi to Nacb pathway caused a homosynaptic
decremental (long-term) potentiation in the Nacb, accompanied by a
heterosynaptic (long-term) depression of the nontetanized BLA to Nacb
pathway. We postulate that the hippocampal inputs may close a
"gate" for the amygdala inputs, whereas the gate is opened for the
hippocampus inputs by previous amygdalar activity. These opposite
effects on the Nacb neuronal populations should be taken into account
when interpreting behavioral phenomena, particularly with respect to
the contrasting effects of the amygdala and the hippocampus in
locomotion and place learning.
Key words:
nucleus accumbens; basolateral amygdala; hippocampus; limbic system; homosynaptic LTP; heterosynaptic LTD; paired-pulse
facilitation; single unit; rat
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INTRODUCTION |
The nucleus accumbens (Nacb) forms a
limbic-motor interface as originally proposed by Heimer and Wilson
(1975) and Mogenson et al. (1980). Indeed, the Nacb receives input from
various limbic structures, including the hippocampal formation
(DeFrance et al., 1980, 1985; Lopes da Silva et al., 1984; Yang and
Mogenson, 1984, 1985; Christie et al., 1987; Groenewegen et al., 1987)
and the basolateral amygdala (BLA) (Krettek and Price, 1978; Yim and
Mogenson, 1982, 1986, 1989; McDonald, 1991; Shinonaga et al., 1994;
Kirouac and Ganguly, 1995; Wright et al., 1996), and projects to areas involved in motor programming, such as the pallidum (Nauta et al.,
1978; Mogenson and Nielsen, 1984; Yang and Mogenson, 1985; Napier et
al., 1995), the midbrain extrapyramidal area (Berendse et al., 1992),
and the dopaminergic cell groups of the substantia nigra and ventral
tegmental area (Nauta et al., 1978; Heimer et al., 1991). The two main
limbic input structures of the Nacb, the amygdala and the hippocampal
formation, can be assigned to distinct behaviors. The amygdala forms a
link between sensory systems and structures involved in emotional
behavior (Davies, 1992; LeDoux, 1993; Adolphs et al., 1995), whereas
the hippocampal formation is important in memory tasks particularly
involving spatial cues (Morris et al., 1982; Zola-Morgan et al., 1986,
1989, 1991; Alvarez et al., 1995).
Taken separately, the hippocampal and amygdaloid inputs to the Nacb
have been anatomically mapped and electrophysiologically characterized.
However, as yet, little is known about how hippocampal and amygdalar
information inputs interact to program behavioral acts. Nevertheless,
we know that locomotion is affected differently by manipulations of
amygdalar or hippocampal circuits. Injections of NMDA in the amygdala
lead to an attenuation of locomotion (Yim and Mogenson, 1989), whereas
NMDA injected in the hippocampus produces an enhancement (Mogenson and
Nielsen, 1984). Both of these effects are completely antagonized by
intra-accumbens administration of an AMPA/kainate antagonist or by
dopamine (Yim and Mogenson, 1989). How such contrasting effects can be
accounted for at the physiological level is unclear because electrical
stimulation of the BLA or the hippocampal formation produces apparently
identical EPSP-IPSP sequences in cells of the Nacb (Yim and Mogenson,
1986; Pennartz and Kitai, 1991). Interactions among excitatory inputs from prefrontal cortex and hippocampus to the Nacb were studied using
in vivo intracellular recordings by O'Donnell and Grace (1995), showing that hippocampal input is necessary for Nacb neurons to
enter an active state. Also, on a small number of Nacb cells, Finch
(1996) has shown convergence of various limbic inputs.
To better understand how amygdalar and hippocampal inputs can modulate
the behavior of Nacb neurons in distinct ways, we mapped the functional
localization of the Nacb neurons with respect to these two main inputs
by stimulating, in vivo in the rat, the BLA and the Fo/Fi.
The cellular responses were recorded, and the patterns of convergence
and segregation of the two inputs were studied. In the areas of
convergence, the interactions between the two inputs were examined
using protocols to induce paired-pulse and long-term
potentiation/depression.
Parts of this work have been published previously in preliminary
form (Mulder et al., 1995a; Mulder and Lopes da Silva, 1996).
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MATERIALS AND METHODS |
Basic surgery and placement of electrodes. Male
Wistar rats (n = 18; ~200 gm) were initially
anesthetized in a chamber (3% halothane in O2 and
N2O) after which the trachea was intubated. Thereafter, the
rats were artificially respirated with a mixture of 0.9% halothane in
O2 and N2O and mounted in a stereotaxic frame. The skull was exposed, and burr holes were made according to the coordinates of the atlas of Pellegrino et al. (1981). All electrodes were zeroed on the interaural line, midline, and cortical surface. Stimulation electrodes (Trimel-coated stainless steel, 60 µm) were
placed in the BLA [anterior (A), 5.0 mm; lateral (L), 5.0 mm; ventral
(V), 7.5 mm) and the Fo/Fi (A, 5.5 mm; L, 1.5 mm; V, 3.5 mm). Single
unit activity and field potentials, evoked by Fo/Fi and/or BLA
stimulation, were recorded in the Nacb (A, 8.5-9.5 mm; L, 1.0-2.5 mm;
V, 5.5-8.0 mm), using glass microelectrodes (10-30 M , filled with
2% pontamine sky blue in acetate buffer, 2 M, pH 8.2). In
every experiment, several penetrations of the Nacb were systematically
performed from the dorsal to the ventral border at various rostrocaudal
and mediolateral coordinates.
Stimulation and data acquisition. Standard bipolar Fo/Fi
and/or BLA stimulation consisted typically of two identical 0.2 msec paired pulses, at an interval of 100 msec, with intensities ranging from 100 to 700 µA and delivered at a low repetition rate (once every
7.5 sec). The first stimulus of the pair is called the
"conditioning" (C) pulse, and the second is called the "test"
(T) pulse. "Evoked field potentials" (EFPs) were amplified
(CyberAmp, Axon Instruments, Foster City, CA) and digitized by way of a
CED 1401 interface (Cambridge Electronic Design, Cambridge, UK) that
was connected to an IBM-PC. Standard sampling rate was set to 5000 samples/sec, and EFPs were averaged (n = 16) and stored
on hard disk. Single-unit activity was bandpass-filtered (500-3500
Hz), and individual single-unit action potentials were separated from
noise using a window discriminator and sampled on-line by a computer
connected to a CED 1401 interface. Peristimulus time histograms were
constructed on-line. The evoked field potentials and the single-unit
activity on stimulation of the Fo/Fi, and/or BLA, were examined in
relation to the location within the Nacb.
Paired-pulse facilitation and long-term potentiation. The
field potentials evoked by Fo/Fi and BLA stimulation at different intensities (input-output curves) were measured separately. In this
way, the stimulation intensity at which the amplitudes of the
corresponding EFPs saturated was determined. In general, an intensity
corresponding to 50% of the saturation level was chosen for the test
stimulus. For quantification, the amplitudes of the rising and decaying
flanks of the synaptic field components of the individual EFPs were
calculated and averaged. The firing probability of single units was
determined; it was defined as the percentage of stimuli that evoked one
action potential at a certain stimulus intensity. Therefore, a firing
probability of 50% relates to a stimulus intensity that has a 50%
chance of eliciting one action potential.
Paired-pulse facilitation (PPF) of the responses of the Nacb was
examined, for both pathways separately, at different interstimulus intervals at the intensity indicated above. Subsequently, the interactions between Fo/Fi and BLA stimulation were investigated by
applying, at different intervals, the conditioning stimulus to the
Fo/Fi and the test stimulus to the BLA or vice versa.
Long-term potentiation (LTP) was elicited in the Nacb by a tetanic
stimulation of the Fo/Fi fibers. This consisted of 100 equidistant
pulses (50 Hz, 2 sec) given near saturation intensity. To establish
baseline controls, EFPs were recorded separately in the Nacb after
Fo/Fi and BLA stimulation, for 15 min, before a single tetanic
stimulation was applied to the Fo/Fi pathway. During the 90 min after
the tetanus, EFPs were recorded in the tetanized pathway (Fo/Fi to
Nacb) and in the nontetanized pathway (BLA to Nacb), in an alternating
sequence. The response of the Nacb during the tetanus and 1 min after
tetanus was monitored continuously to check for the possible occurrence
of after-discharges. The rats in which after-discharges were
encountered were not used in the LTP study.
Histological verification. After all data were recorded, the
electrode placements were marked and the brains were removed. After
immersion fixation (4% paraformaldehyde, 0.05% glutaraldehyde in
phosphate buffer), transverse sections (40 µm) were cut on a freezing
microtome, and a Nissl staining was performed to verify the electrode
placements histologically. These placements were subsequently
transferred to standard levels of the Nacb taken from the atlas of
Paxinos and Watson (1996). In these sections, the representative
shell/core border based on differential calbindin-protein immunoreactivity (Jongen-Rêlo et al., 1994) was indicated (see Fig. 2).
Experimental design and statistical evaluation. Only results
obtained in animals in which all three electrode placements were correct and in which Fo/Fi and BLA stimulation elicited
single-unit responses were included. The cell searching procedure
consisted of a double-pulse protocol giving one pulse to BLA and one to Fo/Fi (or vice versa), with a standard interpulse interval of 100 msec
delivered every 7.5 sec. The number of BLA stimulations matched the
number of Fo/Fi stimulations in the individual rats. Not more than
three electrode tracks in the Nacb per rat were performed. Usually
these tracks were at different mediolateral coordinates. Sites at which
paired-pulse interaction (BLA-Fo/Fi or vice versa) protocols were
delivered were always marked. The deepest recording site of all the
individual electrode tracks was marked. After LTP-inducing protocols,
the recording site was marked and the rat was perfused. All values are
given as mean ± SEM. The results were tested using the Student's
t test for paired comparisons (* = p < 0.05, ** = p < 0.01, *** = p < 0.001), unless stated otherwise.
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RESULTS |
Evoked field potentials
In the Nacb, stimulation of the Fo/Fi caused characteristic field
potentials (Fig. 1), which have been
described previously (Boeijinga et al., 1993; Mulder et al., 1997). In
short, the EFP consisted of two positive synaptic components: the
latency of the first one was 10 msec on average (P10, monosynaptically
driven), and the latency of the second one was 25 msec (P25,
polysynaptically driven) (Fig. 1A1,2,3). In the
entire Nacb, the peaks of the EFPs were of similar amplitude and
latency.
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Figure 1.
Evoked responses recorded in the Nacb. Recording
in the medial shell and medial core regions of the Nacb resulted in
evoked field potentials with positive peak latencies of ~10 and 22 msec to Fo/Fi stimulation (A1) and negative peak
latencies of ~16 msec to BLA stimulation (B1), whereas
in the ventrolateral shell and core regions, on BLA stimulation, EFPs
with longer latencies were recorded (C1). In A2,
B2, and C2, single traces (bandpass-filtered)
show action potentials that coincide with the positive peaks of the
Fo/Fi-induced EFP and the negative peaks of the EFP to BLA stimulation.
Peristimulus time histograms of the single unit activity to Fo/Fi and
BLA stimulation presented in A3, B3, and
C3 were constructed (64 sweeps). Clearly visible is the
peak latency at 9 msec to Fo/Fi stimulation (A3) in the
medial shell/core and the 15 msec (B3) and 23 msec
(C3) peak latency in medial shell/core and ventrolateral
shell/core, respectively, to BLA stimulation. The second peak visible
in B3 after 21 msec is attributable to the occurrence of
an occasional burst of two action potentials.
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On BLA stimulation (Fig. 1), the characteristic EFP consisted of one
clear negativity, with an average latency of 16 msec in the medial part
of the Nacb (Fig. 1B1,2,3) and significantly longer
latencies in the ventrolateral Nacb (Fig. 1C1,2,3).
Single unit activity
In total 154 single units were recorded in the Nacb driven by
Fo/Fi stimulation.
The Nacb units driven by Fo/Fi stimulation were located mainly in the
medial shell/core regions (Fig. 2,
bottom panels). In the lateral shell and the ventral and
lateral core, no Fo/Fi-driven cells were encountered. Also Fo/Fi
responding units were recorded in the ventromedial part of the
caudate-putamen lining the lateral ventricle. The occurrence of action
potentials always coincided with the rising phase or the peak of the
positive components of the EFP, e.g., either the P10 or the P25 (Fig.
1). Within the P10 and P25 ranges, Nacb neurons responded with one
single action potential (no bursts) on a single stimulus. The nature of
the response, either monosynaptic or polysynaptic, was determined by
applying double pulses with short interpulse intervals. The following
criterion was used (based on Laroche et al., 1990; Finch et al., 1995;
Finch, 1996): firing activity able to follow both pulses given at a 4 msec pulse interval and failing to respond to the second pulse when the
interpulse interval was set to 2.5 msec was considered to be
monosynaptic, whereas firing activity already failing at interpulse
intervals of 10-20 msec was labeled polysynaptic. In all areas within
the Nacb mentioned above, monosynaptic responses (n = 111; 9.5 ± 0.1 msec on average) were found, whereas the
polysynaptic single unit activity (n = 74; 21.0 ± 0.2 msec on average) was concentrated mainly in the mid-rostrocaudal
Nacb (Fig. 2, bottom panels). Thirty-one units presented
both monosynaptic and polysynaptic responses. Figure
3 shows the spike latency distribution of
the units of the Nacb driven by Fo/Fi stimulation in which the two
distinct populations of monosynaptic and polysynaptic activation are
clearly visible. The response latency of an individual neuron was based
on at least 16 trials. The action potential latencies of the
monosynaptic responses in the rostral Nacb were significantly longer
compared with the mid-rostrocaudal and caudal regions, whereas in the
mid-rostrocaudal area, medial core latencies are significant longer
than in the medial shell (Table 1).
Therefore, the axis of increasing response latencies of single units
responding to Fo/Fi stimulation runs from the caudomedial to
rostrolateral Nacb.
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Figure 2.
Distribution of single-unit activity within the
Nacb to Fo/Fi and BLA stimulation. The transverse sections are modified
from the atlas of Paxinos and Watson (1996). Three sections from
rostral to caudal Nacb are presented. Top panels, The
boundary between shell and core region (short dashes)
was based on Jongen-Rêlo et al. (1994) in which calbindin protein
staining was used. The circles represent locations where
LTP was elicited in the Nacb to Fo/Fi tetanization. Within the
circles, the left symbol relates to the
Fo/Fi to Nacb pathway, whereas the right symbol is for
the BLA to Nacb pathway.  , Potentiation;  , depression;  , no
effect. + indicates the location where PPF was studied. Bottom
panels, Monosynaptically ( ) and polysynaptically ( )
driven single units to Fo/Fi stimulation and monosynaptically driven
single units to BLA stimulation ( ) are presented. Single units
presenting mono- and polysynaptic responses to Fo/Fi stimulation are
also indicated by filled circles. Single units
responding to both Fo/Fi and BLA stimulation are indicated by
star-shaped symbols (filled,
monosynaptically driven by Fo/Fi; open, polysynaptically
driven by Fo/Fi). Only Fo/Fi-driven units were found in the dorsal
shell and the ventromedial caudate putamen (vm CP),
whereas only BLA-driven activity was recorded in the ventrolateral part
of the Nacb in both shell and core regions. Single units responding to
both stimuli were recorded in the medial shell and medial core
regions.
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Figure 3.
Distribution of the latencies of Nacb single units
driven by Fo/Fi and/or by BLA stimulation. Clearly visible are the two
distinct latencies at which Fo/Fi-driven neurons could be found that
correspond to the two peaks of the evoked field potential P10 and P25.
The BLA-driven units display latencies with peaks at 15 and 19 msec.
These single units were all found in the medial shell and medial core
regions of the Nacb. Neurons displaying latencies of 20 msec and longer
to BLA stimulation were found exclusively in the ventrolateral parts of
the Nacb in both shell and core.
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Table 1.
Firing latency (in msec) of single units driven by Fo/Fi
(monosynaptically at P10 and polysynaptically at P25) or BLA
stimulation in relation to location in the Nacb
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Only a few single units were found in the most medial parts of the
shell and the rostrolateral shell. This may be attributable to a bias
in the electrophysiological protocol: the stimulation electrodes were
located in the intermediate mediolateral part of the Fo/Fi fibers for
excitation of a maximal number of fibers. In this way, fibers in the
(dorso)medial and lateral portions of the Fo/Fi, which reach the
caudomedial and rostrolateral parts of the Nacb (Groenewegen et al.,
1987), respectively, may have been activated suboptimally by our
stimulations.
On stimulation of the BLA, a total of 68 single units were studied in
the Nacb. Single units were recorded in the medial shell/core regions
and in the ventrolateral Nacb in both shell and core areas (Fig. 2,
bottom panels). Action potentials occurred in relation to
the negative field potential (Fig. 1) and could be classified as
monosynaptic. In general, cells responded with a single spike on one
stimulus, although occasionally bursts of two or three action
potentials were recorded, especially on large stimulation intensities
(Fig. 1B3, PSTHs). Figure 3 shows the spike latency distribution of the BLA-driven single units. A population of single units firing with latencies shorter than 20 msec was found in the
medial shell/core regions, whereas single cells with longer latencies
were located exclusively in the ventrolateral Nacb in both shell and
core (Table 1). Also, on BLA stimulation, a few single units
(n = 3; latency 14 ± 1 msec) in the tuberculum
olfactorium were recorded.
Convergence and segregation of inputs within the
nucleus accumbens
A convergence of inputs from the Fo/Fi and BLA was found in 34 cells, mainly in the medial shell but also in the medial core regions
(Fig. 2, bottom panels) and rarely in the dorsomedial part
of the shell and not in the ventrolateral shell and the ventral core
regions or in the ventromedial part of the caudate putamen. In the
dorsomedial shell of the Nacb and the ventromedial part of the caudate
putamen, only Fo/Fi driven cells were encountered, whereas in the
ventrolateral areas of the Nacb in both shell and core only single
units driven by BLA stimulation were found. No differences in response
latencies between cells that are activated only by Fo/Fi and cells that
also received BLA inputs were found (Table 1). The BLA-driven cells in
the medial shell of the caudal area, which presented convergence of
inputs, displayed significantly shorter latencies than those in the
medial shell of the mid-rostrocaudal area (Table 1). The single units
recorded in the ventrolateral areas, which showed no convergence, were
classified as long-latency, and at least in the mid-rostrocaudal area
were significantly longer than the medial shell and core latencies.
Interaction of hippocampal and amygdaloid inputs in the
nucleus accumbens
In the areas of convergence of the monosynaptically driven
Fo/Fi and BLA activity, the interaction between both inputs was studied.
To measure PPF, the firing probabilities of single units were
determined. In the 10 cases studied, PPF could be readily induced in
the Fo/Fi to Nacb pathway as described previously (Boeijinga et al.,
1990) and also in the BLA to Nacb pathway, as shown in the example of
Figure 4. However, when the test stimulus
was given to the BLA preceded by the conditioning stimulus to the Fo/Fi (Fo/Fi + BLA), the firing probability was markedly lower than after a
single BLA stimulation (Fig. 4A). This was observed
in all neurons tested (n = 10), recorded in the area of
convergence. Application of the conditioning pulse to the BLA and the
test pulse to the Fo/Fi (BLA + Fo/Fi) resulted in an increased firing probability of the Fo/Fi response compared with one single Fo/Fi stimulation, but the facilitation was less than in the case of paired
Fo/Fi stimulation (Fig. 4B). Table
2 gives a summary of the PPF data.
Although in general the stimulation intensities were not varied
systematically, we could observe that in an individual cell in which
BLA (50% saturation intensity) response was attenuated after previous
Fo/Fi stimulation (50% saturation intensity), activity was still
decreased when the Fo/Fi was stimulated with an intensity range from 15 to 85% of the saturation intensity.
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Figure 4.
Examples of paired-pulse interactions of the BLA
to Nacb and the Fo/Fi to Nacb pathways. Paired-pulse stimulation of the
BLA results in paired-pulse facilitation (A).
However, when the conditioning pulse is applied to the Fo/Fi fibers and
the test pulse is applied in the BLA, the latter is strongly attenuated
(A) compared with a single BLA conditioning pulse
with the same intensity. Double-pulse stimulation of the Fo/Fi also
results in PPF (B). When the conditioning pulse
is applied in the BLA followed by the test pulse in the Fo/Fi, the
latter response is enhanced compared with a single Fo/Fi conditioning
pulse with the same intensity. The dashed lines
represent the firing probabilities for the conditioning pulses in these
experiments.
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Table 2.
Firing probability of Nacb single units (n = 10) to either BLA or Fo/Fi stimulation or combinations of BLA and
Fo/Fi
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In eight rats, we examined whether long-term potentiation of the Fo/Fi
to Nacb pathway would affect the response to BLA stimulation. In seven
rats this led to the characteristic accumbens decremental LTP (Mulder
et al., 1997), consisting of an initial amplitude increase of ~160%
followed by a decremental form of LTP lasting ~60 min. Unexpectedly,
in six rats we found that during the period of potentiation of the
Fo/Fi to Nacb pathway, the nontetanized BLA to Nacb pathway showed
long-term depression (LTD). In the rat in which the BLA to Nacb
response was not affected by LTP in the Fo/Fi to Nacb pathway, the
recording electrode was located in an area where very little
convergence of the two inputs was observed (Fig. 2). The time courses
of the LTP of the Fo/Fi to Nacb pathway and the LTD of the BLA to Nacb
pathway for the six rats are shown in Figure
5.
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Figure 5.
Long-term interaction between the Fo/Fi and the
BLA to Nacb pathways after tetanization of the former. LTP in the Fo/Fi
to Nacb pathway is presented after a classic tetanus (50 Hz, 2 sec).
The tetanic stimulation was given at t = 0. The LTP
shows the characteristic initial increase followed by the decremental
phase reaching baseline within 60 min as described previously
(Boeijinga et al., 1993; Mulder et al., 1993, 1997). The nontetanized
BLA to Nacb pathway is depressed (LTD) significantly for 90 min. The
bars at the bottom of the graph indicate
the level of significance for the post-tetanic values compared with the
pretetanic controls. Closed bar, Fo/Fi to Nacb;
open bar, BLA to Nacb.
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DISCUSSION |
The primary result of this study is that convergence and
interactions of BLA and hippocampal inputs were found in the medial shell/core regions of the Nacb. In the dorsomedial shell of the Nacb
and the ventromedial caudate-putamen, only Fo/Fi-driven cells were
encountered, whereas in the ventrolateral shell/core only single units
driven by BLA stimulation were found. Second, within the region of
convergence, activation of a single pathway before the other results in
a modulation of the latter, either an enhancement in the case in which
the conditioning stimulus is applied to the BLA and the test to the
Fo/Fi, or a depression in the opposite case. Third, decremental LTP of
the Fo/Fi to Nacb pathway is accompanied by LTD of the nontetanized BLA
to Nacb pathway in regions of the Nacb where convergence was
encountered.
Termination patterns of amygdalar and hippocampal afferents in
the accumbens
The area of convergence corresponds in general to that described
in previous anatomical (Groenewegen et al., 1987; Shinonaga et al.,
1994; Kirouac and Ganguly, 1995; Wright et al., 1996) and
electrophysiological investigations (DeFrance et al., 1980, 1985; Yim
and Mogenson, 1982, 1986, 1989; Yang and Mogenson, 1984, 1985; Calloway
et al., 1991) in which, however, the two pathways were studied
separately.
The distribution of latencies of single units responding to Fo/Fi, the
shortest in the caudal dorsomedial area of the Nacb that increased in
the rostral ventrolateral direction, is consistent with the fact that
the Fo/Fi fibers enter the Nacb from a caudal dorsomedial position,
fanning out in rostral and lateral directions (Groenewegen et al.,
1987).
With respect to the distribution of the electrophysiological responses
to stimulation of the BLA, there was a good correspondence with the
terminal fields of the fibers arising from different subdivisions of
the basal nuclei of the amygdala, as shown by tracing studies (Wright
et al., 1996). Nacb neurons responding to BLA stimulation display
relatively short latencies in the medial shell/core regions (~15 and
19 msec) and longer latencies (20-26 msec) in the ventrolateral shell
and lateral core. These are in line with earlier reports, although no
relationships between latencies and locations in the Nacb were reported
(Yim and Mogenson, 1982, 1986, 1989; O'Donnell and Grace, 1995). A
possible anatomical basis for these differences in latencies is that
the fibers originating in the basal nuclei of the amygdala course
toward the Nacb by two major pathways. Fibers originating in the
rostral two-thirds of the magnocellular basal amygdaloid nucleus reach
the Nacb directly via the external capsule to the ventrolateral shell
and core, whereas all other areas (including the rostral amygdalar
accessory basal and parvicellular basal nuclei) project via the stria
terminalis to medial parts of the Nacb (Kita and Kitai, 1990; Shinonaga
et al., 1994; Wright et al., 1996). Thus, it is likely that these two
routes have different conduction times. In addition, the different peak
latencies found in shell/core neurons (15 and 19 msec) could be
attributable to the fact that the stria terminalis contains slow as
well as fast conducting fibers (Fernandez de Molina and Garcia-Sanchez,
1967).
Both hippocampal and amygdaloid terminals in the Nacb make asymmetrical
synapses, primarily on dendritic spines (Totterdell and Smith, 1989;
Kita and Kitai, 1990; Meredith et al., 1993; Johnson et al., 1994). An
examination of the typical polarity of the field generated by EPSPs in
the Nacb, i.e., positive after Fo/Fi stimulation and negative after BLA
stimulation, and the coincidence of unit firing with these fields allow
us to make some suggestions about the possible distribution of synaptic
inputs. Although Nacb field potentials on Fo/Fi stimulation are
characterized by a positive deflection (Boeijinga et al., 1993; Mulder
et al., 1997), BLA stimulation yields negative field potentials. The
finding that through the entire Nacb similar EFPs were recorded, with polarity changes only at the dorsal and ventral borders (Lopes da Silva
et al., 1984; Mulder et al., 1997), is in line with the fact that the
medium-sized spiny Nacb neurons do not form well defined layers but
have cell bodies occupying a central position surrounded by dendrites
in all directions (DeFrance et al., 1985; Pennartz and Kitai, 1991;
Arts and Groenewegen, 1992). In general terms, extracellular fields are
generated by a combination of sinks, at the site of active excitatory
synaptic contacts, and sources at the remaining part of the
somadendritic membrane (Lopes da Silva, 1996). Therefore, we
hypothesize that the hippocampal afferents terminate on distal parts of
the dendritic tree of Nacb neurons, forming a distal sink that
surrounds the cell body as a narrow ring, whereas the main part of the
cell, i.e., the soma and the proximal dendrites, behaves as an extended
source. Because these neurons overlap, the resultant field will be
dominated by these sources. The finding of negative population spikes
riding the positive peak of the local field potential strengthens this interpretation. However, after stimulation of the BLA, negative population spikes are found to ride local negative field potential components. Accordingly, we assume that BLA excitatory inputs result in
proximal current sinks distributed around the soma and along large
areas of the proximal dendrites. Thus we may hypothesize that the
hippocampal inputs make synaptic contacts primarily with distal
dendrites, whereas the amygdalar synapses are located proximally.
Paired-pulse interactions of amygdalar and hippocampal inputs
Fo/Fi stimulation leads to depression of spontaneous
activity of long duration after an initial excitatory response in the Nacb (Mulder et al., 1997). This inhibitory response is likely mediated
by GABA-B receptors (Gigg et al., 1994; Finch et al., 1995). If the
test stimulus applied to the BLA arrives during this inhibitory period,
as in our experiments, the response would be attenuated. In contrast,
the homosynaptic paired stimulation of the same Fo/Fi input causes
facilitation. The latter is most likely modulated by a strong
presynaptic facilitatory mechanism (Kuhnt and Voronin, 1994) that seems
to be able to mask the inhibitory component.
The mechanism of the facilitatory heterosynaptic effect of a
conditioning BLA input on the test hippocampal response may be accounted for by the fact that BLA inputs, acting on the proximal part
of the somadendritic membrane of the stellate spiny neurons of the
Nacb, depolarize the latter. Accordingly, the hippocampal inputs that
follow a BLA stimulus encounter the soma of the Nacb neurons already in
a depolarized state. This could account for a postsynaptic facilitation
of this form of paired responses.
Decremental long-term potentiation accompanied by heterosynaptic
long-term depression
Decremental LTP in the Nacb after Fo/Fi tetanization has already
been described by us (Boeijinga et al., 1993; Mulder et al., 1993,
1997). The novel finding reported here is that, simultaneously with
this form of LTP, a heterosynaptic LTD was encountered in the BLA
responses. This heterosynaptic depression could be attributable to the
fact that potentiation of the population of cells driven by Fo/Fi may
cause a potentiation of GABAergic inhibition in surrounding cells.
Indeed we found that this form of LTP is accompanied by strong
GABAergic feedforward inhibition in this neuronal population (Mulder et
al., 1995b). This is compatible with an interpretation that
intermingled neuronal populations may respond preferentially to Fo/Fi
or to BLA inputs; however, convergence of hippocampal and BLA inputs
cannot be ruled out. The heterosynaptic LTD may result from a
postsynaptic mechanism (Abraham and Goddard, 1983) that may depress the
activity of synapses of a separate input lying in close proximity to
the tetanized one.
Functional implications
Finally, we put forward the hypothesis that the activity of the
Fo/Fi to Nacb pathway could result in a "closed gate" with respect
to subsequent BLA to Nacb inputs, such as would correspond to a state
in which GABAergic activity in the Nacb is at a high level. In
contrast, BLA inputs would lead to a state of "open gate"; i.e.,
they would be permissive, leading to a state of relatively low
GABAergic activity. O'Donnell and Grace (1995), using intracellular recordings, consider that the hippocampus appears to gate prefrontal cortico-accumbens throughout. However, such gating mechanisms are
likely to depend not only on the nature of the changes of membrane
voltage at the soma, but also on the changes in the dendrites. Taking
into consideration the distributed synaptic inputs along the extensive
dendritic trees of the stellate cells, it would be useful to combine
intracellular and extracellular recordings to obtain a more
comprehensive idea about how these different types of dynamic
"gating" effects take place.
It is relevant to note that the region of the Nacb where the most clear
interactions between hippocampal and amygdalar inputs were found
correspond closely to areas that have as output targets brainstem
structures such as the midbrain extrapyramidal area, the periaqueductal
gray, the ventral tegmental area, and the dopaminergic substantia nigra
pars compacta (Wright et al., 1996). Therefore this type of interaction
between hippocampal and amygdalar inputs in the Nacb, well placed to
influence reward and incentive systems, could play a role in behaviors
such as conditioned place preference in which place learning, probably
mediated by the hippocampal system, depends on the presence of reward,
which is mediated by the amygdalar system.
| |
FOOTNOTES |
Received Sept. 2, 1997; revised April 17, 1998; accepted April 21, 1998.
This work was supported by the foundation for Medical Research
(MEDIGON, Grant 900-550-093) of the Dutch Organization for Scientific
Research (NWO). We thank Professor Dr. H. J. Groenewegen for his
valuable comments on this manuscript.
Correspondence should be addressed to A. B. Mulder, Netherlands
Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam ZO,
The Netherlands.
| |
REFERENCES |
-
Abraham WC,
Goddard GV
(1983)
Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression.
Nature
305:717-719[Medline].
-
Adolphs R,
Tranel D,
Damasio H,
Damasio AR
(1995)
Fear and the human amygdala.
J Neurosci
15:5879-5891[Abstract].
-
Alvarez P,
Zola-Morgan S,
Squire LR
(1995)
Damage to the hippocampal region produces long-lasting memory impairment in monkeys.
J Neurosci
15:3796-3807[Abstract].
-
Arts MPM,
Groenewegen HJ
(1992)
Relationships of the dendritic arborations of ventral striatomesencephalic projection neurons with boundaries of striatal compartments. An in vitro intracellular labelling study in the rat.
Eur J Neurosci
4:574-588[Web of Science][Medline].
-
Berendse HW,
Groenewegen HJ,
Lohman AHM
(1992)
Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat.
J Neurosci
12:2079-2103[Abstract].
-
Boeijinga PH,
Pennartz CMA,
Lopes da Silva FH
(1990)
Paired-pulse facilitation in the nucleus accumbens following stimulation of the subicular inputs in the rat.
Neuroscience
35:301-311[Medline].
-
Boeijinga PH,
Mulder AB,
Pennartz CMA,
Manshanden I,
Lopes da Silva FH
(1993)
Response of the nucleus accumbens following fornix/fimbria stimulation of the rat. Identification and long-term potentiation of mono- and polysynaptic pathways.
Neuroscience
53:1049-1058[Web of Science][Medline].
-
Calloway C,
Hakan RL,
Henriksen SJ
(1991)
Distribution of amygdala input to the nucleus septi: an electrophysiological investigation.
J Neural Transmembr
83:215-225.
-
Christie MJ,
Summers RJ,
Stephenson JA,
Cook CJ,
Beart PM
(1987)
Excitatory amino acid projections to the nucleus accumbens septi in the rat: A retrograde transport study utilizing d[3H]aspartate and [3H]GABA.
Neuroscience
22:425-439[Web of Science][Medline].
-
Davies M
(1992)
The role of the amygdala in conditioned fear.
In: The amygdala, neurobiological aspects of emotion, memory, and mental dysfunction (Aggleton JP,
ed), pp 255-305. New York: Wiley.
-
DeFrance JF,
Marchand J,
Stanley JC,
Sikes RW,
Chronister RB
(1980)
Convergence of excitatory amygdaloid and hippocampal input in the nucleus accumbens septi.
Brain Res
185:183-186[Medline].
-
DeFrance JF,
Marchand JF,
Sikes RW,
Chronister RB,
Hubbard JI
(1985)
Characterization of fimbria input to nucleus accumbens.
J Neurophysiol
54:1553-1567[Abstract/Free Full Text].
-
Fernandez de Molina A,
Garcia-Sanchez JL
(1967)
The properties of the stria terminalis fibers.
Physiol Behav
2:225-227.
-
Finch DM
(1996)
Neurophysiology of converging synaptic inputs from rat prefrontal cortex, amygdala, midline thalamus, and hippocampal formation onto single neurons of the caudate/putamen and nucleus accumbens.
Hippocampus
6:495-512[Web of Science][Medline].
-
Finch DM,
Gigg J,
Tan AM,
Kosoyan OP
(1995)
Neurophysiology and neuropharmacology of projections from entorhinal cortex to striatum in the rat.
Brain Res
670:233-247[Medline].
-
Gigg J,
Tan AM,
Finch DM
(1994)
Glutamatergic hippocampal formation projections to prefrontal cortex in the rat are regulated by GABAergic inhibition and show convergence with glutamatergic projections from the limbic thalamus.
Hippocampus
4:189-198[Web of Science][Medline].
-
Groenewegen HJ,
Vermeulen-Van Der Zee E,
te Kortschot A,
Witter MP
(1987)
Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of phaseolus vulgaris leucoagglutinin.
Neuroscience
23:103-120[Web of Science][Medline].
-
Heimer L,
Wilson RD
(1975)
The subcortical projections of the allocortex: similarities in the neural associations of the hippocampus, the piriform cortex, and the neocortex.
In: Perspectives in neurobiology. Golgi centennial symposium (Santini M,
ed), pp 177-193. New York: Raven.
-
Heimer L,
Zahm DS,
Churchill L,
Kalivas PW,
Wohltmann C
(1991)
Specificity in the projection patterns of the accumbal core and shell in the rat.
Neuroscience
41:89-125[Web of Science][Medline].
-
Johnson LR,
Aylward RL,
Hussain Z,
Totterdell S
(1994)
Input from the amygdala to the rat nucleus accumbens: its relationship with tyrosine hydroxylase immunoreactivity and identified neurons.
Neuroscience
61:851-865[Web of Science][Medline].
-
Jongen-Rêlo A,
Voorn P,
Groenewegen HJ
(1994)
Immunohistochemical characterization of the shell and core territories of the nucleus accumbens in the rat.
Eur J Neurosci
6:1255-1264[Web of Science][Medline].
-
Kirouac GJ,
Ganguly PK
(1995)
Topographical organization in the nucleus accumbens of afferents from the basolateral amygdala and efferents to the lateral hypothalamus.
Neuroscience
67:625-630[Web of Science][Medline].
-
Kita H,
Kitai ST
(1990)
Amygdaloid projections to the frontal cortex and the striatum in the rat.
J Comp Neurol
298:40-49[Web of Science][Medline].
-
Krettek JE,
Price JL
(1978)
Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat.
J Comp Neurol
178:225-254[Web of Science][Medline].
-
Kuhnt U,
Voronin LL
(1994)
Interaction between paired pulse facilitation and long-term potentiation in area CA1 of guinea-pig hippocampal slices: application of quantal analysis.
Neuroscience
62:391-397[Web of Science][Medline].
-
Laroche S,
Jay TM,
Thierry AM
(1990)
Long-term potentiation in the prefrontal cortex following stimulation of the hippocampal CA1/subicular region.
Neurosci Lett
114:184-190[Web of Science][Medline].
-
LeDoux JE
(1993)
Emotional memory systems in the brain.
Behav Brain Res
58:69-79[Web of Science][Medline].
-
Lopes da Silva FH
(1996)
The generation of electric and magnetic signals of the brain by local networks.
In: Comprehensive human physiology, Vol 1 (Gregor R,
Windhorst U,
eds), pp 509-531. Berlin: Springer.
-
Lopes da Silva FH,
Arnold DEAT,
Neijt HC
(1984)
A functional link between the limbic cortex and ventral striatum: physiology of the subiculum-accumbens pathway.
Exp Brain Res
55:205-214[Web of Science][Medline].
-
McDonald AJ
(1991)
Topographical organization of amygdaloid projections to the caudatoputamen, nucleus accumbens, and related striatal-like areas of the rat brain.
Neuroscience
44:15-33[Web of Science][Medline].
-
Meredith GE,
Pennartz CMA,
Groenewegen HJ
(1993)
The cellular framework for chemical signalling in the nucleus accumbens.
Prog Brain Res
99:3-24[Web of Science][Medline].
-
Mogenson GJ,
Nielsen M
(1984)
A study of the contribution of hippocampal-accumbens-subpallidal projections to locomotor activity.
Behav Neural Biol
42:38-51[Medline].
-
Mogenson GJ,
Jones DL,
Yim CY
(1980)
From motivation to action: functional interface between the limbic system and the motor system.
Prog Neurobiol
14:69-97[Web of Science][Medline].
-
Morris RGM,
Garrud P,
Rawlins JNP,
O'Keefe J
(1982)
Place navigation impaired in rats with hippocampal lesions.
Nature
297:681-683[Medline].
-
Mulder AB,
Lopes da Silva FH
(1996)
Interaction of the hippocampus and the basolateral amygdala inputs to the nucleus accumbens.
Soc Neurosci Abstr
22:911.
-
Mulder AB,
Arts MPM,
Lopes da Silva FH
(1993)
Long term potentiation simultaneously induced in nucleus accumbens, prefrontal cortex, and hippocampus.
Neurosci Res Commun
13:11-14.
-
Mulder AB,
Gijsberti Hodenpijl M,
Lopes da Silva FH
(1995a)
Electrophysiology of the hippocampal and basolateral amygdaloid inputs to the nucleus accumbens of the rat: patterns of convergence and segregation.
Eur J Neurosci [Suppl]
8:151.
-
Mulder AB,
Zuiderwijk M,
Lopes da Silva FH
(1995b)
Enhancement of long-term potentiation in the nucleus accumbens by removal of GABAergic inhibition.
Pflügers Arch
430:R177.
-
Mulder AB,
Arts MPM,
Lopes da Silva FH
(1997)
Short- and long-term plasticity of the hippocampus to nucleus accumbens and prefrontal cortex pathways in the rat, in vivo.
Eur J Neurosci
9:1603-1611[Web of Science][Medline].
-
Napier TC,
Mitrovic I,
Churchill L,
Klitenick MA,
Lu XY,
Kalivas PW
(1995)
Substance P in the ventral pallidum: projection from the ventral striatum, and electrophysiological and behavioral consequences of pallidal substance P.
Neuroscience
69:59-70[Web of Science][Medline].
-
Nauta WJH,
Smith GP,
Faull RL,
Domesick VB
(1978)
Efferent connections and nigral afferents of the nucleus accumbens in the rat.
Neuroscience
3:385-401[Web of Science][Medline].
-
O'Donnell P,
Grace AA
(1995)
Synaptic interactions among excitatory afferents to nucleus accumbens neurons: hippocampal gating of prefrontal cortical input.
J Neurosci
15:3622-3639[Abstract].
-
Paxinos G,
Watson C
(1996)
In: The rat brain in stereotaxic coordinates. New York: Academic.
-
Pellegrino LJ,
Pellegrino AS,
Cushman AJ
(1981)
In: A stereotaxic atlas of the rat brain, Ed 2. New York: Plenum.
-
Pennartz CMA,
Kitai ST
(1991)
Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: evidence for feed-forward inhibition.
J Neurosci
11:2838-2847[Abstract].
-
Shinonaga Y,
Takada M,
Mizuno N
(1994)
Topographic organization of collateral projections from the basolateral amygdaloid nucleus to both the prefrontal cortex and the nucleus accumbens in the rat.
Neuroscience
58:389-397[Web of Science][Medline].
-
Totterdell S,
Smith AD
(1989)
Convergence of hippocampal and dopaminergic input onto identified neurons in the nucleus accumbens of the rat.
J Chem Neuroanat
2:285-298[Web of Science][Medline].
-
Wright CI,
Beijer AVJ,
Groenewegen HJ
(1996)
Basal amygdaloid complex afferents to the rat nucleus accumbens are compartmentally organized.
J Neurosci
16:1877-1893[Abstract/Free Full Text].
-
Yang CR,
Mogenson GJ
(1984)
Electrophysiological responses of neurons in the nucleus accumbens to hippocampal stimulation and the attenuation of the excitatory responses by the mesolimbic dopaminergic system.
Brain Res
324:69-84[Web of Science][Medline].
-
Yang CR,
Mogenson GJ
(1985)
An electrophysiological study of the neural projections from the hippocampus to the ventral pallidum and the subpallidal areas by way of the nucleus accumbens.
Neuroscience
15:1015-1024[Web of Science][Medline].
-
Yim CY,
Mogenson GJ
(1982)
Response of nucleus accumbens neurons to amygdala stimulation and its modification by dopamine.
Brain Res
239:401-415[Web of Science][Medline].
-
Yim CY,
Mogenson GJ
(1986)
Mesolimbic dopamine projection modulates amygdala-evoked EPSP in nucleus accumbens neurons: an in vivo study.
Brain Res
369:347-352[Medline].
-
Yim CY,
Mogenson GJ
(1989)
Low doses of nucleus accumbens dopamine modulate amygdala suppression of spontaneous exploratory activity in rats.
Brain Res
477:202-210[Medline].
-
Zola-Morgan S,
Squire LR,
Amaral DG
(1986)
Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus.
J Neurosci
6:2950-2967[Abstract].
-
Zola-Morgan S,
Squire LR,
Amaral DG
(1989)
Lesions of the hippocampal formation but not lesions of the fornix or the mammillary nuclei produce long-lasting memory impairments in monkeys.
J Neurosci
9:898-913[Abstract].
-
Zola-Morgan S,
Squire LR,
Alvarez-Royo P,
Clower RP
(1991)
Independence of memory functions and emotional behaviour: separate contributions of the hippocampal formation and the amygdala.
Hippocampus
1:207-220[Medline].
Copyright © 1998 Society for Neuroscience 0270-6474/98/18135095-08$05.00/0
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Top
Abstract
Introduction
