Download Similar Inhibitory Processes Dominate the Responses of Cat Lateral

Similar Inhibitory Processes Dominate the Responses of Cat Lateral
Amygdaloid Projection Neurons to Their Various Afferents
E. J. LANG AND D. PARÉ
Département de Physiologie, Université Laval, Québec, Québec G1K 7P4, Canada
INTRODUCTION
The amygdala is critical for imbuing sensory stimuli with
the appropriate emotional significance (Adolphs et al. 1995;
Bechara et al. 1995). The lateral amygdaloid (LAT) nucleus, a major recipient of cortical and thalamic sensory
pathways to the amygdala (Amaral et al. 1992; LeDoux et
al. 1985; Romanski and LeDoux 1992; Russchen 1982b;
Turner et al. 1980) and source of afferents to other amygdaloid nuclei (Krettek and Price 1978; Pitkänen et al. 1995;
Smith and Paré 1994; Stefanacci et al. 1992), appears to be
a necessary link for the development of auditory conditioned
fear responses (LeDoux et al. 1986, 1990). Characterization
of the mechanisms governing LAT neuronal activity therefore is required for understanding the neuronal basis of these
responses and more generally of emotional expression.
Recent evidence suggests that local inhibitory processes
are major determinants of LAT neuronal activity and are
central to its normal functioning as, for example, a decrease
in GABAergic neurons within this structure is correlated
with the development of kindled seizures (Callahan et al.
1991). In single unit studies, LAT neurons were found to
have very low firing rates (Ben-Ari et al. 1974; Bordi et al.
1993), with the majority of projection neurons being virtually silent unless presented with a specific sensory stimulus
(Gaudreau and Paré 1996). Moreover, in vitro studies have
shown that synaptic responses in the basolateral amygdaloid
(BL) complex are characterized by large inhibitory postsynaptic potentials (IPSPs) (Rainnie et al. 1991b; Sugita et al.
1993; Takagi and Yamamoto 1981; Washburn and Moises
1992). In agreement with these physiological findings, synaptic boutons immunoreactive for glutamic acid decarboxylase (GAD) are concentrated strategically around the soma,
proximal dendrites and axonal initial segment of amygdaloid
projection cells (Carlsen 1988).
Inhibition within the LAT nucleus must arise largely from
GABAergic neurons located within the LAT nucleus itself,
as lesions deafferenting the BL complex lead to minor decreases in GAD levels (Le Gal La Salle et al. 1978). Moreover, although other amygdaloid nuclei contain GABAergic
interneurons (McDonald 1985; Nitecka and Ben-Ari 1987;
Paré and Smith 1993), internuclear projections linking the
different nuclei of the BL complex appear to consist only
of excitatory projections (Paré et al. 1995c; Smith and Paré
1994). An intriguing finding, therefore, was that both spontaneous and evoked g-aminobuturic acid-A (GABAA ) and
GABAB responses could occur independently in LAT neurons recorded in vitro (Sugita et al. 1992), suggesting that
the LAT nucleus contains two distinct GABAergic neuronal
populations, each having access to different types of
GABAergic receptors.
Given the importance of inhibitory processes in the functioning of the amygdala, and to test the possibility that separate interneuronal populations are accessed differentially by
0022-3077/97 $5.00 Copyright q 1997 The American Physiological Society
/ 9k0b$$ja43
08-13-97 18:02:07
neupal
LP-Neurophys
341
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
Lang, E. J. and D. Paré . Similar inhibitory processes dominate
the responses of cat lateral amygdaloid projection neurons to
their various afferents. J. Neurophysiol. 77: 341 – 352, 1997. To
investigate the impact of inhibitory processes on responses of
lateral amygdaloid ( LAT ) neurons, intracellular recordings were
obtained from identified LAT projection neurons in barbiturateanesthetized cats. Synaptic responses evoked by perirhinal
( PRH ) , entorhinal ( ENT ) , basomedial, and LAT stimulation
were investigated. Regardless of stimulation site, responses consisted of an excitatory postsynaptic potential (EPSP ) that either
preceded and was truncated by an inhibitory postsynaptic potential ( IPSP) or occurred just after the IPSP onset. IPSPs were
monophasic, lasted hundreds of milliseconds, and were of such
large amplitude and rapid onset that they effectively opposed the
EPSPs, generally preventing orthodromic spikes. All sites elicited
IPSPs with relatively negative reversal potentials around 085
mV. Experiments analyzing the underlying ionic mechanisms are
presented in the companion paper. Evoked responses were similar
to synaptic potentials associated with spontaneous EEG events,
known as simple ( small, monophasic ) and complex (large, triphasic ) ENT sharp potentials ( SPs) , with no difference between the
reversals of evoked and SP-related IPSPs ( 083.2 { 2.7 mV ) .
IPSPs coinciding with complex SPs truncated SP-related EPSPs
more rapidly and had larger amplitudes and longer durations than
those related to simple SPs. These differences reflected the fact
that the amplitude and duration of SP-related IPSPs were correlated with SP amplitude. Similar variations were reproduced in
evoked IPSPs by varying the stimulus intensity. Low intensities
generated predominantly excitatory responses consisting of
EPSPs sometimes followed by small IPSPs, whereas high intensities evoked predominantly inhibitory responses comprised of a
large IPSP that truncated or occluded the EPSPs. Orthodromic
spikes were elicited only in a narrow range of intermediate intensities. These changes in the evoked response primarily reflected
increases in the IPSP evoked at high intensities. PRH stimulation
at different rostro-caudal levels demonstrated that rostral sites
elicited larger EPSPs and IPSPs with shorter latencies and longer
durations than caudal sites. These differences probably reflect
contrasting patterns of activity spread through the PRH cortex,
suggesting that the intact cortical circuitry allowed a temporally
distributed activation of inhibitory interneurons and thereby partly
explains the long duration and monophasic nature of the IPSPs.
Inhibition, thus, plays a primary role in shaping LAT neuronal
responses. The profuse intrinsic connectivity of the LAT nucleus
and parahippocampal cortices may underlie the relatively invariant response pattern of LAT neurons and suggests a common
mode of information processing, based upon quantitative, rather
than qualitative, differences in activation of LAT circuitry. Therefore we propose that effective transmission of signals through the
LAT nucleus may require activation of specifically sized neuronal
ensembles, rather than widespread afferent excitation.
342
E. J. LANG AND D. PARÉ
particular amygdaloid afferents, we sought to characterize
the IPSPs of intracellularly recorded LAT projection neurons
in vivo. Our results demonstrate that powerful IPSPs regulate
the response of LAT neurons to their synaptic inputs and
that their response pattern is relatively constant irrespective
of the stimulation site. Further, evidence was obtained that
feedback inhibition within the LAT nucleus is mediated by
similar IPSPs. This uniformity suggests that distinct
GABAergic subpopulations cannot be independently accessed in vivo. Instead, the degree of activation within a
particular afferent pathway was found to be critical in shaping the synaptic responses of LAT neurons.
METHODS
metrics, OR) data analysis software. For each cell, measurement
of IPSP amplitudes were performed at the same time for each
potential. This time corresponded to when the IPSP reached its
maximal amplitude at the most depolarized tested level. The IPSP
reversal potential was then determined by plotting the IPSP amplitude as a function of Vm . The input resistance (RIN ) before and
during an IPSP was estimated by calculation of the slope resistance
(the reciprocal of the slope conductance) (Johnston and Wu 1995).
Here the change in voltage from the resting Vm was plotted against
the DC current level, and the slope of the fitted line was used to
estimate the RIN of the cell. Although I-V curves showed deviations
from linearity, the comparison of the slope resistance before and
during IPSPs remained useful for estimating the impact of IPSPs.
Linear fits were performed with the least-squares method as calculated by the computer program IGOR (Wavemetrics, OR).
Histology
Intracellular recordings were obtained from adult cats (2.5–3.5
kg) anesthetized with sodium pentobarbital (Somnotol, 40 mg/kg
ip), paralyzed with gallamine triethiodide (33 mg/kg iv), and
ventilated artificially. The level of anesthesia was determined by
continuously monitoring the electroencephalograph (EEG), and
supplemental doses of Somnotol (5–7 mg/kg iv) were given as
needed to maintain a synchronized EEG pattern. Lidocaine (2%)
was applied to all skin incisions. End tidal CO2 concentration was
kept at 3.7 { 0.2% (mean { SE), and the rectal temperature was
maintained at 37–387C with a heating pad. To ensure recording
stability, the cisterna magna was drained, the cat suspended, and
a bilateral pneumothorax performed.
The bone and dura mater overlying the parietal and temporal
cortices were removed, allowing a lateral approach to the amygdala
and a dorsal approach to the perirhinal (PRH) and entorhinal
(ENT) cortices. Pairs of tungsten electrodes (0.5 MV ) whose tips
were separated by 1.5 mm in the vertical axis, or concentric bipolar
tungsten electrodes were used to record the PRH and ENT EEG
activity and to apply local electrical stimuli (100–200 ms pulses,
100–1,500 mA, at 0.2–1 Hz). The tungsten electrodes were implanted stereotactically into the PRH and ENT cortices with one
electrode of each pair in the superficial (I-II) and deep cortical
layers (IV-V), respectively. The exact dorsoventral coordinate was
obtained by lowering the ENT electrodes until they contacted the
temporal bone and then raising them to their correct position using
the EEG criteria of positive or negative going sharp potentials as
indicative of superficial or deep cortical layers, respectively (Paré
et al. 1995a). The dorsoventral position of the electrodes in the
PRH cortex was corrected as a function of the difference between
the stereotaxically predicted (Berman and Jones 1982) and actual
positions of the ENT cortex. The ENT electrodes were placed into
the ventromedial ENT area.
Histological controls were performed to confirm the stimulation
electrode positions and the morphology of the recorded cells. At
the conclusion of the experiment, the animal was perfused with
500 ml of chilled saline (0.9%) followed by 1 l of a solution of
2% paraformaldehyde and 1% glutaraldehyde in 0.1 M phosphate
buffered saline (PBS, pH 7.4). The brain was stored in 30% glucose solution overnight and then transferred to PBS. Coronal sections (80 mm) were cut on a freezing microtome. Neurobiotin filled
cells were visualized by incubating the sections in the avidinbiotin-horseradish peroxidase (HRP) solution (ABC Elite Kit,
Vector Labs) and processed to reveal the HRP staining (Horikawa
and Armstrong 1988). The positions of stimulation electrodes were
verified in thionin-stained sections.
Recording procedure
Intracellular recording electrodes consisted of glass capillary
tubes pulled to a tip diameter of É0.5 mm (35–45 MV ). The
electrodes were filled with K / -acetate (4 M) and Neurobiotin (14
mg/mL; Vector Labs). They were lowered obliquely 6 mm through
the posterior sylvian gyrus to the border of the LAT nucleus using
a piezoelectric manipulator. The exposed cortical surfaces then
were covered with agar to improve recording stability.
Intracellular recordings were made using a high impedance amplifier with active bridge circuitry (Neurodata, NY). Typically,
cells were recorded for 30 min to 2 h. After penetration and stabilization of impalements, spontaneous and evoked synaptic potentials
were recorded at different membrane potentials (Vms) induced by
DC current injection. The intracellular and EEG signals were monitored using a digital oscilloscope, printed out on a chart recorder,
and stored on VCR tape for off-line analysis using IGOR (Wave-
/ 9k0b$$ja43
RESULTS
Stable intracellular recordings were obtained from 74
LAT neurons with stable resting potentials greater than or
equal to 065 mV ( 072.6 { 1.3 mV; mean { SE; n Å
74), and spike amplitudes ranging between 60 and 90 mV.
Eighteen percent of them were identified formally as projection neurons using morphological and/or physiological criteria (Fig. 1). In agreement with previous Golgi studies (for
review, McDonald 1992), neurobiotin-filled neurons were
considered as projection cells when they had spiny dendrites
with a stellate or a modified pyramidal somatodendritic morphology. An example of a morphologically identified LAT
neuron is shown in Fig. 1A1, along with a high-power photomicrograph of a spiny dendritic segment (Fig. 1A2).
Physiological identification of LAT projection cells rested
on eliciting antidromic responses by PRH or ENT stimulation (Fig. 1B). All neurons described in this study displayed
similar electroresponsive properties known to be characteristic of LAT projection cells including lack of spontaneous
discharges at rest, time- and voltage-dependent rectification,
and generation of voltage-dependent oscillations in the 4–
10 Hz range upon steady membrane depolarization to around
065 mV (Pape and Paré 1995; Paré et al. 1995b).
Recordings of spontaneous activity revealed synaptic
events typically consisting of truncated excitatory postsynaptic potentials (EPSPs) followed by large (5–15 mV) hyperpolarizing potentials. These intracellular events often were
related to spontaneous EEG waves in the PRH and ENT
cortices, termed sharp potentials (SPs) (Paré et al. 1995a).
For brevity, we will henceforth refer to evoked and SPrelated hyperpolarizing potentials as IPSPs; however, we
demonstrate in the accompanying paper that they actually
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
Surgery
INHIBITION IN THE LATERAL AMYGDALOID NUCLEUS
343
FIG . 1. Morphological and physiological identification of lateral amygdaloid (LAT) projection neurons. A1:
photomicrograph of a spiny stellate LAT neuron filled
with Neurobiotin. A2: high magnification of a spiny dendritic segment. B1: perirhinal (PRH)-evoked antidromic
spikes. Superimposed responses to 12 PRH stimuli (arrowhead) showing constant spike latency. Note that spike
arises directly from baseline without a preceding excitatory postsynaptic potential (EPSP). B2: superimposed
antidromic responses to high-frequency (250 Hz) trains
of 3 and 5 PRH stimuli (arrowheads). Note ability of
antidromic spikes to follow high-frequency stimulation.
Cortical and intra-amygdaloid stimuli evoke similar IPSPs
To test whether different afferents generate distinct IPSPs
in LAT neurons, synaptic responses were evoked from several brain regions connected with this nucleus, including the
PRH and ENT cortices as well as the basomedial (BM)
nucleus. The latter was stimulated in an attempt to evoke
recurrent inhibition, as this nucleus receives a massive input
from the LAT nucleus but does not reciprocate this projection (Krettek and Price 1978). In addition, the LAT nucleus
itself was stimulated to assess the influence of intrinsic connections. Histological controls confirmed the electrode
placements in these regions (Fig. 3, A–D). In the PRH
cortex, a series of four electrodes was placed along its rostrocaudal extent as shown schematically in Fig. 3A1.
Cortical stimuli (PRH, Fig. 3A2; ENT, Fig. 3B) evoked
similar responses with respect to the PSP sequence, IPSP
amplitude, and reversal potential. The latency of cortically
evoked IPSPs (from the site eliciting the shortest latency
response) was 4.8 { 0.5 ms (range, 2.8–7.3 ms; n Å 8),
whereas the BM-evoked IPSPs had a slightly longer latency
of 6.6 { 0.9 ms (range, 2.1–10.8 ms; n Å 8). These differences did not reach significance (P õ 0.1).
/ 9k0b$$ja43
The monophasic IPSPs evoked from cortical and BM sites
typically had reversal potentials ranging from 080 to 090
mV (cortex, 084.7 { 1.3 mV, n Å 17; BM, 082.1 { 0.9
mV, n Å 4) and were not significantly different (P õ 0.2).
In particular, IPSPs evoked in the same cells by PRH and
BM stimulation had closely matched reversal potentials. In
the cell of Fig. 4, A and B, for example, PRH-evoked IPSPs
(Fig. 4A1) reversed at 083.1 mV, whereas BM-evoked
IPSPs (Fig. 4A2) reversed at 081.9 mV, nearly the same
potential (Fig. 4A3). In this cell, BM stimulation evoked
IPSPs of lower amplitude that were associated with a smaller
drop in RIN (55%, Fig. 4B2) than PRH-evoked IPSPs (83%,
Fig. 4B1). However, there were large variations between
cells in the RIN drops related to IPSPs.
In a further attempt to reveal a second, distinct type of
inhibitory response, IPSPs were evoked by direct stimulation
of the LAT nucleus. However, placement of stimulation electrodes in the LAT nucleus altered the properties of the cells
(higher RINs and more depolarized resting potentials and
IPSP reversals). Consequently, this stimulation site was used
in only two experiments. These IPSPs had a latency of 4 {
0.5 ms (n Å 3), consistently shorter than BM- or cortically
evoked IPSPs. However, their reversal potentials ( 080.4 {
0.6 mV, n Å 3) were similar to those of IPSPs elicited by
cortical ( 078.9 { 0.7 mV, n Å 3) and BM ( 080.4 { 0.2
mV, n Å 3) stimulation in the same cells. Figure 4C illustrates LAT-evoked responses in a LAT projection cell. In
this case, the IPSP reversed around 079.6 mV (Fig. 4C1)
and was associated with a 71% drop in RIN (Fig. 4C3).
Similarly, ENT- and BM-evoked IPSPs reversed at 077.5
and 080.5 mV and produced 32 and 68% decreases in RIN ,
respectively.
SP-related IPSPs
To determine whether the uniform properties of the
evoked IPSPs reflected the artificial nature of electrical stimuli, we compared them with synaptic events occurring spontaneously in relation to simple (monophasic) and complex
(triphasic) SPs that occur in the ENT and PRH cortices
under barbiturate anesthesia (Fig. 2) and during slow-wave
sleep (Paré and Gaudreau 1996; Paré et al. 1995a). The
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
are generated by a combination of synaptic and synapticallyactivated intrinsic conductances (Lang and Paré 1997).
An example is shown in Fig. 2B1 where the intracellular
trace (INTRA) displays numerous IPSPs that occurred in
association with SPs (Fig. 2B1, top; ENT) or in response
to a PRH stimulus (arrowhead). Depolarization to 060 mV
with /0.6 nA led to sustained spiking (Fig. 2A), which
was interrupted by large SP-related IPSPs (curved arrows)
lasting °500 ms. The IPSPs could occur in relation to either
simple (monophasic, Fig. 2C1) or complex (triphasic, Fig.
2C2) SPs, as demonstrated by perievent averages of intracellular events using the negative peak (arrows in Fig. 2C) of
SPs as a temporal reference.
Cortically evoked responses were similar to SP-related
intracellular potentials in amplitude and duration (Fig. 2B2).
Like SP-related IPSPs, cortically evoked IPSPs often had
small postsynaptic potentials (PSPs) embedded within them
(Fig. 2D, arrowheads).
344
E. J. LANG AND D. PARÉ
average reversal potential of SP-related IPSPs was 083.8 {
2.7 mV (n Å 7), which was not statistically different from
the reversal potential of IPSPs evoked by cortical and BM
stimuli (P ú 0.50). Furthermore, there was a high correlation between the reversal potential of evoked and SP-related
IPSPs (r Å 0.87, P õ 0.05) in the same cells. Additionally,
the reversal potentials of simple and complex SP-related
IPSPs were compared and found to be nearly identical
( 086.3 { 5.9 mV, simple SP-related; 086.4 { 5 mV, complex SP-related; n Å 3).
Simple and complex SP-related IPSPs recorded at different Vms in the same cell are shown in Fig. 5B. The IPSPs
were aligned using the negative peak of the related SPs
shown in Fig. 5A. In this cell, simple and complex SPrelated IPSPs reversed at similar values of 093.5 and 091
mV, respectively. ENT-evoked responses also reversed at a
relatively negative value of 087.5 mV.
It was found consistently that the amplitude of SP-related
IPSPs was related to the size of the SP. This relationship
was most clearly observed when comparing simple and complex SP-related IPSPs because of the large amplitude difference between the two SP types (Figs. 2, A and B, 5, and
6). As shown in the peri-SP averages of Fig. 2C, IPSPs
related to simple SPs had a lower amplitude than those related to complex SPs (Simple, 2.2 { 0.2 mV; Complex,
6.9 { 0.5 mV, n Å 6 at 065 mV; P õ 0.00005, paired ttest). In addition to their larger amplitude, complex SPrelated IPSPs curtailed the initial EPSP more rapidly and
/ 9k0b$$ja43
had a longer duration. Superimposed traces of simple SPrelated synaptic potentials (Fig. 6B) and complex SP-related
ones (Fig. 6C) demonstrate these differences. Thus, while
the initial EPSPs are similar in amplitude, the ones related
to complex SPs are significantly narrowed (Complex, 21.5
{ 10.4 ms; Simple, 59.3 { 15.2 ms, n Å 6, P õ 0.02) and
have a steeper falling phase than the simple SP-related
EPSPs (Fig. 6, B–D). Further, comparison of the averaged
potentials shows the longer duration of the complex SPrelated IPSP (Fig. 6D; Simple, 318.3 { 38.4 ms; Complex,
556.2 { 66.8 ms, n Å 6, P õ 0.002). This duration difference remained even after scaling the simple SP-related IPSP
(Fig. 6E), suggesting that the complex SP triggers not only
a larger amplitude potential, but also one that lasts longer.
Synaptic responses of LAT neurons vary with stimulation
intensity
The parallel fluctuations between, on the one hand, the
amplitude of SPs, and on the other, the nature of SP-related
potentials, suggested that the balance between excitatory and
inhibitory inputs converging on a LAT neuron might depend
on the degree of activation in a LAT afferent pathway, additionally, so might the IPSP duration. To verify this, synaptic
responses were evoked by PRH and BM stimulation at varying intensities, and a common response profile was observed
(n Å 17). At very low intensities, depolarizing responses
typically were observed. However, with increasing intensi-
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
FIG . 2. Spontaneous activity of LAT projection cells is
dominated by large amplitude inhibitory postsynaptic potentials (IPSPs). A and B: bipolar electroencephalographic recording of entorhinal (ENT) cortex (top) and simultaneously recorded LAT neuron (bottom). In A, depolarizing
current injection (0.6 nA to approximately 060 mV) induced
tonic firing except during large IPSPs that were related to
spontaneous ENT sharp potentials (SPs). B: same cell at
rest ( 072 mV). Note absence of spontaneous spikes and
dominant IPSPs. Small EPSPs also were present, but often
appeared truncated by large amplitude IPSPs. Arrowhead
points to PRH stimulus artifact. Intracellular events labeled
by asterisks in B1 are expanded in B2. C: peri-event average
of intracellular potentials using negative peak (F ) of simple
(C1) and complex (C2) SPs. D: ENT-evoked IPSPs from
a depolarized level (D1) and from rest (D2).
INHIBITION IN THE LATERAL AMYGDALOID NUCLEUS
345
are truncated more and more rapidly as the response becomes
predominantly hyperpolarizing at higher intensities.
The duration of the IPSP always was found to vary directly with stimulus intensity (n Å 17). Thus higher intensities produced IPSPs that could last several hundred milliseconds longer than IPSPs elicited at lower intensities. An example is shown in Fig. 7C, where IPSPs evoked by different
intensities were scaled to have equal peak amplitudes. The
responses evoked by the lower intensity stimuli, whereas
peaking at a similar time as the responses evoked by the
higher intensity shocks, had steeper decays leading to their
more rapid termination (Fig. 7C). In addition, IPSP duration
was measured from response onset to the time when the
potential had decreased to 25% of the peak IPSP amplitude.
A plot of duration as a function of stimulus intensity also
showed the direct relation between IPSP duration and stimulus intensity (Fig. 7D).
FIG . 3. Histological controls showing location of stimulation electrodes.
A1: scheme showing placement of PRH stimulation electrodes (S1–S4)
on a ventral view of cat brain. Remaining panels are thionin-stained coronal
sections showing positions of stimulation electrodes placed in PRH (A2)
and ENT (B) cortices, as well as in LAT ( C), and basal (D) amygdaloid
nuclei. Curved arrows point to tips of stimulating electrodes. Scale bar in
C and D is also valid for B. BL, basolateral amygdaloid nucleus; BM,
basomedial amygdaloid nucleus; CEL, central lateral amygdaloid nucleus;
CEM, central medial amygdaloid nucleus; DG, dentate gyrus; ENT, entorhinal cortex; EC, external capsule; GP, globus pallidus; L, lateral amygdaloid
nucleus; OB, olfactory bulb; ON, optic nerve; OT, optic tract; PRH, perirhinal cortex; rs, rhinal sulcus.
ties, these depolarizing responses decreased in size and then
became dominated by large hyperpolarizing potentials. The
shape of the depolarizing potential also varied with stimulus
intensity, having a broad shape at lower intensities (lasting
for 100–200 ms), but narrowing to 5–10 ms or completely
disappearing at higher ones. The IPSP shape also was found
to vary with stimulus intensity, but in contrast to the EPSP,
both its amplitude and duration grew monotonically with
stimulus intensity.
A typical response, in this case evoked by PRH stimulation, is shown in Fig. 7A. Here the cell was depolarized to
062 mV with 0.21 nA DC current, and synaptic responses
were evoked with intensities ranging from 0.23 to 1.5 mA
(weaker shocks failed to elicit consistent responses). Depolarizing responses were evoked by the lower intensities
(0.23, 0.25 mA), whereas the higher ones elicited hyperpolarizing responses; small depolarizing potentials embedded
in the IPSP provided evidence that EPSPs continued to be
elicited at the higher intensities (Fig. 7B).
In cases where the EPSP preceded the IPSP onset (65%,
n Å 11), evidence was obtained that the EPSPs would have
continued to increase in size if not for the countering effects
of the IPSP. For example, the PRH-evoked EPSPs in Fig.
8A increased in amplitude with stimulus intensity (compare
EPSPs of 0.33, 0.50, and 0.83 mA traces), even though they
/ 9k0b$$ja43
Anatomic studies in cats have demonstrated that PRH
projections to the LAT nucleus arise from the entire extent
of the PRH cortex, although rostral levels contribute a denser
projection (Russchen 1982a; Witter and Groenewegen
1986). To investigate the degree of PRH convergence onto
individual LAT neurons, the PRH cortex was stimulated at
different rostrocaudal sites (Fig. 9A). In all cells (n Å 10),
synaptic responses could be evoked from the entire extent
of the PRH cortex with all sites showing similar intensity
dependent response profiles, IPSP reversal potentials, and
difficulty in evoking orthodromic spikes.
Nevertheless, some consistent differences emerged. First,
stimulation of caudal PRH levels evoked smaller responses
than were elicited from more rostral sites. For example, in
the cell shown in Fig. 8, stimuli of identical strength (0.83
mA) evoked increasingly large EPSPs and IPSPs when applied at more rostral sites (compare S1, S2, and S3 in Fig.
8, A–C, respectively). Only very high stimulus intensities
(1 mA) applied at the most caudal site (S4) produced IPSPs
of comparable size. Further, the more rostral sites had lower
thresholds for evoking EPSPs (compare minimal intensities
for S1 and S2 versus S3 and S4 in Fig. 8).
Yet, the generation of an orthodromic spike depended less
on the absolute size of the synaptic potentials than on the
balance between the competing EPSPs and IPSPs evoked
by the stimulus. Thus orthodromic spikes could be elicited
from any level of the PRH cortex, not just from the site with
the largest EPSPs. However, each PRH site elicited spikes
only within a narrow range of stimulus intensities. For example, S3 at 0.23 mA readily evoked spikes whereas other
intensities produced subthreshold synaptic potentials (Fig.
8C). In the cell of Fig. 8, only subthreshold responses to
S1, S2, and S4 are displayed for clarity.
PSP onset and duration vary systematically with PRH
stimulus site
Onset latency, defined as the first sustained deflection
from baseline, whether positive or negative (as the evoked
IPSP sometimes preceded the EPSP), was found to increase
as the distance between the LAT nucleus and the stimulation
site increased (Fig. 9, A and D). The average response laten-
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
Synaptic responses evoked from different PRH locations
346
E. J. LANG AND D. PARÉ
cies to S1–S4 were 4.8 { 0.5, 5.9 { 0.7, 10.3 { 1.9, 29 {
3.5, respectively (n Å 8, P õ 0.05). An example of this
latency shift is shown in Fig. 9B.
The onset latency of PRH-evoked PSPs also was found
to decrease with increasing stimulus intensity. The magnitude of this effect, however, depended on the stimulation
site. Rostral sites had not only shorter onset latencies but
also displayed less latency variations with changes in intensity. Thus in Fig. 9, the most caudal site evoked IPSPs at
latencies of 17 and 6.2 ms with low and high intensities,
compared with 6 and 2.5 ms with the rostral-most site.
The duration of PRH-evoked IPSPs (as defined above)
also varied systematically with stimulation location, with
more rostral sites evoking longer duration PSPs compared
with caudal sites. In the example shown in Fig. 9C, the IPSP
duration evoked by S4 was 409 ms compared with 528 ms
at S1 and intermediate values with S2 and S3. As with onset
latency, the duration varied with stimulation distance (Fig.
9D); however, the change in duration was 13.2 ms/mm,
some 30-fold greater than the latency variations (0.4
ms/mm).
FIG . 4. IPSPs evoked by cortical and intra-amygdaloid stimuli have
similar reversal potentials. A: IPSPs elicited at different Vms by PRH (A1)
and BM (A2) stimulation in same LAT neuron. Each trace in this and the
following figures is an average of 4–9 individual sweeps, unless otherwise
stated. Evoked responses consist of a short latency EPSP followed by a
long lasting IPSP. Although PRH stimulation evoked larger synaptic potentials than did BM stimuli in this cell, evoked IPSPs had similar reversal
potentials. Rest Å 071 mV. A3: plot of IPSP amplitude ( DV) at IPSP peak
vs. Vm as determined by DC current injection. Zero-crossing of fitted lines
gives reversal potentials of IPSPs. B: plots of voltage change from resting
potential ( DV) vs. DC current (I) before stimulation (RIN ) and at IPSP
peak (RPEAK ) for PRH- (B1) and BM- (B2) evoked IPSPs. RIN estimated
from slopes of fitted lines (slope resistance). C: IPSPs evoked by direct
LAT stimulation in a different neuron. C1: IPSPs evoked from different
Vm as determined by DC current injection. C2: plot of IPSP amplitude
( DV) at IPSP peak vs. Vm . IPSP reversal potential of 079.6 mV was similar
to those obtained for ENT- and BM-evoked IPSPs in this cell ( 077.5 and
080.5 mV, respectively). See text. Rest Å 065 mV. C3: plots of voltage
change from resting potential ( DV) vs. DC current (I) before stimulation
(RIN ) and at IPSP peak (RPEAK ). At its peak, IPSP reduced RIN by Ç71%.
/ 9k0b$$ja43
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
FIG . 5. Reversal potentials of simple and complex SP-related IPSPs. A:
averaged bipolar recordings of ENT SPs and related intracellular events
(B) recorded at different Vms ( 0106 to 061 mV) as determined by DC
current injection. Simple SP-related IPSPs reversed at 093.5 mV whereas
complex SP-related IPSPs reversed at a similar value ( 091 mV). ENTevoked IPSPs had a slightly more depolarized reversal potential ( 087.5
mV) in this cell. Rest Å 076 mV.
INHIBITION IN THE LATERAL AMYGDALOID NUCLEUS
347
related synaptic potentials; there is a large degree of convergence onto LAT neurons from widespread regions of the
PRH cortex; and synaptic response profiles are highly dependent on stimulus intensity, implying a competitive interaction between excitatory and inhibitory inputs in the LAT
nucleus.
Origin of inhibition within the LAT nucleus
FIG . 6. Intracellular correlates of simple and complex SPs. A: average
of 6 simple (A1) and 4 complex (A2) ENT SPs and related intracellular
events (B and C, respectively). Same LAT neuron in B and C. Traces were
aligned in relation to negative peak of the SPs. D: superimposition of
averaged simple and complex SP-related synaptic potentials. Note larger
size of complex SP-related IPSPs. E: superimposition of averaged complex
and scaled-simple SP-related synaptic potentials. In D and E, arrows point
to EPSPs and IPSPs related to simple SPs. Simple SP-related IPSP was
scaled to have same peak amplitude as averaged complex SP-related IPSP.
Calibration bars in C are for B–E. All postsynaptic potentials obtained at
065 mV with 0.6 nA. Rest Å 078 mV.
DISCUSSION
Previous work has shown that projection neurons of the
LAT nucleus have very low firing rates (Gaudreau and Paré
1996; Paré and Gaudreau 1996), and that GABAergic inhibition may be an important factor in this respect. Thus the
present investigation was undertaken to study how IPSPs
affect the behavior of LAT projection neurons in vivo. Our
results demonstrate that large amplitude, long-lasting monophasic IPSPs reversing around 085 mV dominate the activity
of LAT cells; electrical stimuli applied in major input and
output structures of the LAT nucleus evoke relatively invariant synaptic responses that are similar to spontaneous SP-
/ 9k0b$$ja43
FIG . 7. Synaptic response profiles vary with stimulation intensity. LAT
neuron with resting Vm of 074 mV depolarized to 062 mV by current
injection (0.21 nA). A: synaptic responses to PRH stimuli of different
intensities (mA, numbers on right). Initial part of responses are shown at
a faster sweep speed in B. Note transition from depolarizing to hyperpolarizing responses with increasing stimulus intensity. C: superimposition of
several traces from A after scaling to the same peak IPSP amplitude. D:
plot of IPSP duration versus stimulus intensity. IPSP duration was measured
from response onset to time when potential had decreased to 25% of peak
IPSP amplitude.
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
Although glycinergic IPSPs of unknown origin have been
observed in the LAT nucleus (Danober and Pape 1995),
GABA appears to be the main inhibitory transmitter in the
BL complex. For instance, in vitro studies of LAT and BL
neurons have shown that synaptically evoked IPSPs are sensitive to GABAA- and/or GABAB-receptor antagonists (Danober and Pape 1995; Rainnie et al. 1991b; Sugita et al.
1992, 1993; Washburn and Moises 1992). These IPSPs presumably resulted from the activation of local GABAergic
interneurons as lesions deafferenting the amygdala produce
little if in any decreases in GAD levels (Le Gal La Salle et
al. 1978) and internuclear connections linking the different
BL nuclei only consist of excitatory projections (Paré et al.
1995c; Smith and Paré 1994).
348
E. J. LANG AND D. PARÉ
Thus it is likely that in the present study, the hyperpolarizing potentials elicited by cortical and subcortical stimuli in
LAT projection neurons were mediated mostly by GABAergic interneurons of the LAT nucleus. However, as shown in
the companion paper (Lang and Paré 1997) and in a recent
in vitro study (Danober and Pape 1996), a synaptically activated intrinsic conductance also contributed to these hyperpolarizing potentials.
In vivo IPSP profile differs from that found in vitro
In the in vitro studies of LAT and BL neurons (Rainnie et
al. 1991a,b; Sugita et al. 1992, 1993; Washburn and Moises
1992), responses to afferent stimulation typically consisted
of an early glutamatergic EPSP followed by a biphasic IPSP
comprising an early Cl 0-mediated phase lasting Ç50 ms,
and a late, longer-lasting, K / -mediated component. The
pharmacological sensitivity of these two IPSP phases sug-
/ 9k0b$$ja43
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
FIG . 8. Synaptic responses evoked from different PRH sites. Synaptic
responses were evoked in same neuron from 4 different stimulation sites
along rostrocaudal extent of PRH cortex: S1 (A), S2 (B), S3 (C), and S4
(D). See scheme in Fig. 3A1 for relative positions of stimulating electrodes.
Each panel depicts responses to a range of intensities (mA, values on right).
gested that they resulted from the activation of GABAA and
GABAB receptors, respectively. The early and late IPSPs
also could be distinguished by their reversal potentials
(Rainnie et al. 1991b; Sugita et al. 1992, 1993; Washburn
and Moises 1992). In LAT neurons for instance, the IPSP
reversals were similar to those reported in other CNS neurons, i.e., around 070 mV for GABAA and 0110 mV for
GABAB mediated IPSPs (Sugita et al. 1993).
In addition, in vitro observations indicated that spontaneous and evoked GABAA and GABAB responses could occur
independently in LAT neurons (Sugita et al. 1992), thus
suggesting that the LAT nucleus contains two distinct
GABAergic neuronal populations, each having access to different types of GABAergic receptors.
Although the present results confirmed some of the basic
in vitro findings, such as the near coincident activation of a
fast EPSP and IPSP and the presence of a long-lasting IPSP,
significant differences were observed. First, spontaneous and
evoked IPSPs were monophasic. That is, a clear separation
of the IPSP into distinct early and late components was not
observed in vivo. Second, these monophasic IPSPs (measured at their peak) reversed around 085 mV, a value in
between those typically reported for GABAA and GABAB
IPSPs, suggesting that Cl 0 and K / conductances contributed
to the IPSP. Third, the electrophysiological features of
evoked IPSPs were constant, irrespective of the stimulation
site.
It could be argued that the use of barbiturates in our experiments has obscured the break between an early GABAA and
late GABAB component because barbiturates prolonged the
mean open time of GABAA channels (Barker and McBurney
1979), thus prolonging GABAA-mediated IPSPs (Thompson
and Gähwiler 1992). However, biphasic GABAergic
responses indistinguishable from those observed in vitro
have been described in thalamocortical neurons intracellularly recorded in cats anesthetized with various drugs including urethane, sodium pentobarbital, and ketamine-xylazine
(Contreras et al. 1996; Paré et al. 1991; Paré and Lang,
unpublished results). Yet, pentobarbital perfusion has been
shown to reduce GABAB IPSPs in neurons of the BL nucleus
in vitro (Rainnie et al. 1991b).
IPSPs evoked by stimulating various input and output
structures of the LAT nucleus were studied in an attempt
to test the possibility that the LAT nucleus contains two
populations of GABAergic interneurons having access to
either GABAA or GABAB receptors and being involved in
distinct intra-amygdaloid circuits (Sugita et al. 1992). Stimulation of the PRH and ENT cortices, basal forebrain (results
not shown) as well as intra-amygdaloid stimuli (BM nucleus) all evoked similarly shaped monophasic IPSPs that
reversed around 085 mV. Moreover, IPSPs evoked by direct
LAT stimulation were monophasic, and had nearly identical
reversal potentials to those of the BM- and cortically evoked
IPSPs in the same cells.
BM stimulation was employed in an attempt to selectively
evoke feedback inhibition, because this nucleus is a major
target of LAT neurons (Krettek and Price 1978; Pitkänen et
al. 1995; Russchen 1982b; Smith and Paré 1994; Wakefield
1979) and does not reciprocate this projection (with the
exception of a minor projection to the ventromedial border
of the LAT nucleus) (Paré et al. 1995c). Moreover, LAT
projection neurons give off numerous collaterals before leav-
INHIBITION IN THE LATERAL AMYGDALOID NUCLEUS
349
ing the LAT nucleus (McDonald 1992; Millhouse and
DeOlmos 1983), which presumably contact projection cells
and interneurons (Paré et al. 1995c).
This attempt to demonstrate feedback inhibition was only
partly successful in that the overlapping ranges of latencies
of the BM- and PRH-evoked IPSP prevented us from ruling
out the possibility that the BM-evoked IPSPs were mediated
via an amygdalo-cortico-LAT loop rather than through antidromic activation of recurrent collaterals. Nevertheless, in
at least some cells, the onset of the IPSP and/or EPSP was
too fast (i.e., less than twice the shortest latency of a PRHevoked IPSP) for the initial part of the response to be mediated via a cortical loop. Thus in these cases at least, the
initial components of BM-evoked PSPs were mediated by
feedback excitation and inhibition.
In light of these considerations, the finding that BM- and
cortically evoked IPSPs were indistinguishable suggests that
feedback IPSPs are mediated by the same interneurons responsible for the cortically evoked feed-forward inhibition.
Again, this interpretation is subject to the caveat that a contribution from feed-forward inhibition due to cortical afferents
cannot be excluded, particularly at later times during the
IPSP. This indirect recruitment of cortical inputs may have
obscured differences in shape or reversal potential.
Conversely, it is possible that feedback inhibition, resulting from antidromic activation of cortically projecting
LAT neurons, contributed to cortically evoked IPSPs. However, although the LAT nucleus projects to the entire rostro-
/ 9k0b$$ja43
caudal extent of the PRH in cats (Room and Groenewegen
1986), the projection to the ENT is limited to ventrolateral
ENT area (Smith and Paré 1994), whereas we stimulated
the more caudally situated ventromedial ENT area. Because
no consistent differences between ENT- and PRH-evoked
IPSPs were found, either the contribution of feedback inhibition to PRH-evoked IPSPs is minimal relative to the feedforward inhibition or both types of inhibition involve the
same interneuronal population.
In sum, the relatively invariant nature of the evoked IPSPs,
regardless of stimulation site and their similarity to SP-related
IPSPs, lead us to conclude that independent activation of interneuronal subpopulations contacting only GABAA or GABAB
receptors, respectively, appears not to occur in vivo. This difference from the in vitro situation may be ascribed to the intactness
of the cortical and amygdaloid circuitry in vivo, which probably
links the activation of the different GABAergic populations.
Given the reported barbiturate-sensitivity of GABAB IPSPs in
some neurons (Rainnie et al. 1991b), this conclusion should
be verified under other anesthetics. However, the results of the
companion paper suggest that we were able to detect GABAB
IPSPs and that they never occurred independently of GABAA
IPSPs (Lang and Paré 1997).
Convergence and divergence in corticoamygdaloid
afferents
The discrepancies between the in vivo and in vitro data
appear to result from several factors, including the apparent
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
FIG . 9. IPSP onset and duration vary with PRH stimulation site. A: scheme showing position of PRH stimulation
electrodes on a ventral view of cat brain. B: initial part of
responses are shown at fast sweep speed. Arrows indicate
onset of responses. C: evoked response to identical stimuli
applied at each site. Open circles, points where IPSP amplitudes have decreased to 25% of peak amplitudes. D: plot
of IPSP duration and onset as a function of electrode location in terms of frontal plane level. Intracellular recordings
were obtained at a frontal plane of Ç12 mm. E: schematics
showing postulated flow of activity after stimulation of
rostral (E1) or caudal (E2) PRH sites.
350
E. J. LANG AND D. PARÉ
/ 9k0b$$ja43
A balance of excitation and inhibition
The large IPSPs observed here in vivo, and previously in
vitro (Sugita et al. 1992, 1993; Takagi and Yamamoto
1981), must play an important role in shaping the responses
of LAT neurons. Consistent with these intracellular observations, the large majority of LAT neurons have transient (i.e.,
1–2 spikes) responses to sustained auditory stimuli (Bordi
and LeDoux 1992), Moreover, in a double shock paradigm
of medial geniculate inputs, LAT neurons were found to
have a reduced response to stimuli for delays °150 ms
(Clugnet et al. 1990).
The present results suggest that this inhibition is due to
activation of much the same intra-LAT circuitry and intrinsic
conductances, regardless of the afferent source activated.
Instead, the balance of inhibition and excitation evoked from
a particular site, appears to depend most strongly on the
stimulus intensity, with low intensities producing depolarizing responses and high intensities hyperpolarizing ones.
Given the large degree of divergence in the PRH-LAT projection, this pattern may result from the more extensive dendritic trees of the projection cells as compared with those
of interneurons (Hall 1972). Thus projection neurons would
be more likely to receive synaptic inputs from a particular
source than inhibitory interneurons. Therefore low intensity
stimuli could produce excitation of projection neurons while
still subthreshold for evoking firing of interneurons. With
higher stimulus intensities, interneurons would fire, and because of their strategically located synapses onto the soma
and proximal dendrites (Carlsen 1988), inhibit the projection neurons, despite their receiving increasingly strong excitatory input.
Thus we propose that information processing in the LAT
nucleus may be linked to quantitative, rather than qualitative
differences in activation of intra-LAT circuitry, with the
balance of excitation and inhibition being more relevant than
the absolute magnitude of the evoked responses, or the particular afferent stimulated, for determining the response of
a LAT neuron. Thus we predict that large-scale generalized
activity in LAT afferents should not be as effective in activating the LAT nucleus as would the activity of relatively
small cortical neuronal ensembles. Simultaneous recordings
from the PRH cortex and LAT nucleus should be performed
to address these issues.
The authors thank P. Giguère and G. Oakson for excellent technical and
programming support, D. Drolet for help with the preparation of the figures,
and S. Charpak for stimulating discussions.
E. J. Lang was supported by a National Institute of Neurological Disorders and Stroke Grant 1 F32 NS-10006-01. This study was supported by
the Medical Research Council of Canada (Grant MT-11562).
Address reprint requests to D. Paré.
Received 7 May 1996; accepted in final form 27 September 1996.
REFERENCES
ADOLPHS, R., TRANEL, D., DAMASIO, H., AND DAMASIO, A. R. Fear and the
human amygdala. J. Neurosci. 15: 5879–5891, 1995.
AMARAL, D. G., PRICE, J. L., PITK Ä NEN, A., AND CARMICHEAL, S. T. Anatomical organization of the primate amygdaloid complex. In: The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction, edited by J. P. Aggleton. New York: Wiley-Liss, 1992, p. 1–66.
BARKER, J. L. AND MC BURNEY, R. M. Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurones.
Proc. R. Soc. Lond. B Biol. Sci. 206: 319–327, 1979.
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
down regulation of the GABAB IPSP and the presence of a
synaptically activated Ca 2/ -dependent K / conductance in
vivo. These will be treated in detail in the companion paper
(Lang and Paré 1997). Here we will discuss the role of the
extensive intra-amygdaloid and intracortical connectivity,
which is largely lost with in vitro preparations, in shaping
the temporal characteristics of the evoked responses in vivo.
In our experiments, the extensive convergence of cortical
inputs on LAT neurons was demonstrated by the possibility
of evoking synaptic responses in LAT neurons from all
levels of the PRH cortex as well as from the ENT cortex.
A previous in vivo study performed in rats also demonstrated
that LAT neurons receive convergent inputs from multiple
sources (Mello et al. 1992). The variations in amplitudes
and onset latencies of PRH-evoked IPSPs as a function of
the stimulation site were consistent with the anatomic data
on PRH projections to the LAT nucleus. Thus the shorter
latency of responses to rostral PRH stimuli is consistent with
the shorter distance separating the LAT nucleus from rostral
PRH levels as compared with caudal PRH sites (Fig. 9E).
In addition, the larger size of the responses evoked from
rostral sites fits with the denser projection of rostral PRH
levels to the LAT nucleus (Russchen 1982a; Witter and
Groenewegen 1986; Witter et al. 1986).
Given the extensive corticocortical connections within the
PRH cortex and considering the fact that the entire PRH
cortex projects to the LAT nucleus (Russchen 1982a; Witter
and Groenewegen 1986; Witter et al. 1986), the PRHevoked IPSPs must have resulted from the direct activation
of corticoamygdaloid neurons at the stimulation site and
from the activation, via corticocortical circuits, of such neurons throughout a great extent of the PRH cortex (Fig. 9E).
Consequently, PRH inputs arising from different rostrocaudal levels reach the LAT nucleus asynchronously, producing
a temporally distributed activation of LAT inhibitory interneurons that might cause the ‘‘early’’ and ‘‘late’’ inhibitory
responses seen in vitro to overlap, thus explaining the lack
of a clear break between the GABAA and GABAB responses
in vivo. In parallel with the spread of activity at the cortical
level, intrinsic connections within the LAT nucleus (Krettek
and Price 1978; Pitkänen et al. 1995; Russchen 1982b; Smith
and Paré 1994) also must contribute to distribute PRH influences in time and space.
In addition, it is likely that this spread of activity across
the cortex is partly responsible for the longer duration of
IPSPs evoked from rostral PRH sites as compared with caudal ones, since stimuli applied at rostral levels would recruit
the shortest corticoamygdaloid pathways first and the longest
pathways last (Fig. 9E1), resulting in a relatively longer
activation of LAT interneurons. In contrast, IPSPs evoked
by stimulation of caudal PRH sites would be relatively compressed in time because the longer corticoamygdalar fibers
would be activated before the shorter ones (Fig. 9E2). However, given the differences in IPSP latencies from these sites,
which reflect the differing conduction times, only 10–20%
of the duration difference can be accounted for in this manner. The remaining difference must be due to other mechanisms that lead to a more sustained activation of LAT interneurons and/or to greater activation of the inhibitory intrinsic membrane conductances present in LAT projection
neurons.
INHIBITION IN THE LATERAL AMYGDALOID NUCLEUS
/ 9k0b$$ja43
MILLHOUSE, O. E. AND DEOLMOS, J. Neuronal configurations in lateral and
basolateral amygdala. Neuroscience 10: 1269–1300, 1983.
NITECK A, L. AND BEN-ARI, Y. Distribution of GABA-like immunoreactivity
in the rat amygdaloid complex. J. Comp. Neurol. 266: 45–55, 1987.
PAPE, H.-C. AND PARÉ, D. Rhythmic electrical activity in the amygdala:
observations in vitro and in vivo. Soc. Neurosci. Abstr. 21: 1666, 1995.
PARÉ, D., CURRÓ DOSSI, R., AND STERIADE, M. Three types of inhibitory
post-synaptic potentials generated by interneurons in the anterior thalamic
complex of the cat. J. Neurophysiol. 66: 1190–1205, 1991.
PARÉ, D., DONG, J., AND GAUDREAU, H. Amygdalo-entorhinal relations and
their reflection in the hippocampal formation: generation of sharp sleep
potentials. J. Neurosci. 15: 2482–2503, 1995a.
PARÉ, D. AND GAUDREAU, H. Projection cells and interneurons of the lateral
and basolateral amygdala: distinct firing patterns and differential relation
to theta and delta rhythms in conscious cats. J. Neurosci. 16: 3334–
3350, 1996.
PARÉ, D., PAPE, H.-C., AND DONG, J. Bursting and oscillating neurons
of the cat basolateral amygdaloid complex in vivo: electrophysiological
properties and morphological features. J. Neurophysiol. 74: 1179–1191,
1995b.
PARÉ, D. AND SMITH, Y. Distribution of GABA immunoreactivity in the
amygdaloid complex of the cat. Neuroscience 57: 1061–1076, 1993.
PARÉ, D., SMITH, Y., AND PARÉ, J.-F. Intra-amygdaloid projections of the
basolateral and basomedial nuclei in the cat: phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron microscopic level.
Neuroscience 69: 567–583, 1995c.
PITK Ä NEN, A., STEFANACCI, L., FARB, C. R., GO, G.-G., LEDOUX, J. E.,
AND AMARAL, D. G. Intrinsic connections of the rat amygdaloid complex:
projections originating in the lateral nucleus. J. Comp. Neurol. 356: 288–
310, 1995.
RAINNIE, D. G., ASPRODINI, E. K., AND SHINNICK-GALLAGHER, P. Excitatory
transmission in the basolateral amygdala. J. Neurophysiol. 66: 986–998,
1991a.
RAINNIE, D. G., ASPRODINI, E. K., AND SHINNICK-GALLAGHER, P. Inhibitory
transmission in the basolateral amygdala. J. Neurophysiol. 66: 999–1009,
1991b.
ROMANSKI, L. M. AND LEDOUX, J. E. Equipotentiality of thalamo-amygdala
and thalamo-cortico-amygdala circuits in auditory fear conditioning. J.
Neurosci. 12: 4501–4509, 1992.
ROOM, P. AND GROENEWEGEN, H. J. Connections of the parahippocampal
cortex in the cat. II. Subcortical afferents. J. Comp. Neurol. 251: 451–
473, 1986.
RUSSCHEN, F. T. Amygdalopetal projections in the cat. I. Cortical afferent
connections. A study with retrograde and anterograde tracing techniques.
J. Comp. Neurol. 206: 159–179, 1982a.
RUSSCHEN, F. T. Amygdalopetal projections in the cat. II. Subcortical afferent connections. A study with retrograde tracing techniques. J. Comp.
Neurol. 207: 157–176, 1982b.
SMITH, Y. AND PARÉ, D. Intra-amygdaloid projections of the lateral nucleus
in the cat: PHA-L anterograde labeling combined with postembedding
GABA and glutamate immunocytochemistry. J. Comp. Neurol. 342:
232–248, 1994.
STEFANACCI, L., FARB, C. R., PITK Ä NEN, A., GO, G., LEDOUX, J. E., AND
AMARAL, D. G. Projections from the lateral nucleus to the basal nucleus
of the amygdala: a light and electron microscopic PHA-L study in the
rat. J. Comp. Neurol. 323: 586–601, 1992.
SUGITA, S., JOHNSON, S. W., AND NORTH, R. A. Synaptic inputs to GABAA
and GABAB receptors originate from discrete afferent neurons. Neurosci.
Lett. 134: 207–211, 1992.
SUGITA, S., TANAK A, E., AND NORTH, R. A. Membrane properties and synaptic potentials of three types of neurone in rat lateral amygdala. J.
Physiol. Lond. 460: 705–718, 1993.
TAK AGI, M. AND YAMAMOTO, C. The long-lasting inhibition recorded in
vitro from the lateral nucleus of the amygdala. Brain Res. 206: 474–478,
1981.
THOMPSON, S. M. AND GÄHWILER, B. H. Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice
cultures. J. Neurophysiol. 67: 1698–1701, 1992.
TURNER, B. H., MISHKIN, M., AND KNAPP, M. Organization of the amygdalopetal projections from modality-specific cortical association areas in
the monkey. J. Comp. Neurol. 191: 515–543, 1980.
WAKEFIELD, C. The intrinsic connections of the basolateral amygdaloid
nuclei as visualized with the HRP method. Neurosci. Lett. 12: 17–21,
1979.
08-13-97 18:02:07
neupal
LP-Neurophys
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
BECHARA, A., TRANEL, D., DAMASIO, H., ADOLPHS, R., ROCKLAND, C.,
AND DAMASIO, A. R. Double dissociation of conditioning and declarative
knowledge relative to the amygdala and hippocampus in humans. Science
Wash. DC 269: 1115–1118, 1995.
BEN-ARI, Y., LE GAL LA SALLE, G., AND CHAMPAGNAT, J. Lateral amygdala
unit activity. I. Relationship between spontaneous and evoked activity.
Electroencephalogr. Clin. Neurophysiol. 37: 449–461, 1974.
BERMAN, A. L. AND JONES, E. G. The Thalamus and Basal Telencephalon
of the Cat. Madison, WI: University of Wisconsin Press, 1982.
BORDI, F. AND LEDOUX, J. Sensory tuning beyond the sensory system: an
initial analysis of auditory response properties of neurons in the lateral
amygdaloid nucleus and overlying areas of the striatum. J. Neurosci. 12:
2493–2503, 1992.
BORDI, F., LEDOUX, J., CLUGNET, M. C., AND PAVLIDES, C. Single-unit
activity in the lateral nucleus of the amygdala and overlying areas of the
striatum in freely behaving rats: rates, discharge patterns, and responses
to acoustic stimuli. Behav. Neurosci. 107: 757–769, 1993
CALLAHAN, P. M., PARIS, J. M., CUNNINGHAM, K. A., AND SHINNICK-GALLAGHER, P. Decrease of GABA-immunoreactive neurons in the amygdala
after electrical kindling in the rat. Brain Res. 555: 335–339, 1991.
CARLSEN, J. Immunocytochemical localization of glutamate decarboxylase
in the rat basolateral amygdaloid nucleus, with special reference to GABAergic innervation of amygdalostriatal projection neurons. J. Comp.
Neurol. 273: 513–526, 1988.
CLUGNET, M. C., LEDOUX, J. E., AND MORRISON, S. F. Unit responses
evoked in the amygdala and striatum by electrical stimulation of the
medial geniculate body. J. Neurosci. 10: 1055–1061, 1990.
CONTRERAS, D., TIMOFEEV, I., AND STERIADE, M. Mechanisms of longlasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks. J. Physiol. Lond. 494: 251–264, 1996.
DANOBER, L. AND PAPE, H.-C. Slow inhibitory synaptic responses in amygdaloid nuclei. Soc. Neurosci. Abstr. 21: 1666, 1995.
DANOBER, L. AND PAPE, H.-C. Contribution of a slow membrane hyperpolarization to the prevention of epileptic activity in the lateral amygdala.
Soc. Neurosci. Abstr. 22: 822.14, 1996.
GAUDREAU, H. AND PARÉ, D. Projection neurons of the lateral amygdaloid
nucleus are virtually silent throughout the sleep-waking cycle. J. Neurophysiol. 75: 1301–1305, 1996.
HALL, E. The amygdala of the cat: a golgi study. Z. Zellforsch. 134: 439–
458, 1972.
HORIK AWA, K. AND ARMSTRONG, W. E. A versatile means of intracellular
labeling: injection of biocytin and its detection with avidin conjugates.
J. Neurosci. Methods 25: 1–11, 1988.
JOHNSTON, D. AND WU, S. M.-S. Foundations of Cellular Neurophysiology.
Cambridge, MA: Bradford Book/MIT Press, 1995.
KRETTEK, J. E. AND PRICE, J. L. A description of the amygdaloid complex
in the rat and cat with observations on intra-amygdaloid axonal connections. J. Comp. Neurol. 178: 255–280, 1978.
LANG, E. J. AND PARÉ, D. Synaptic and synaptically activated intrinsic
conductances underlie inhibitory potentials in cat lateral amygdaloid projection neurons in vivo. J. Neurophysiol. 77: 353–363, 1997.
LE GAL LA SALLE, G., PAXINOS, G., EMSON, P., AND BEN-ARI, Y. Neurochemical mapping of GABAergic systems in the amygdaloid complex
and bed nucleus of the stria terminalis. Brain Res. 155: 397–403, 1978.
LEDOUX, J. E., CICCHETTI, P., XAGORARIS, A., AND ROMANSKI, L. M. The
lateral amygdaloid nucleus: sensory interface of the amygdala in fear
conditioning. J. Neurosci. 10: 1062–1069, 1990.
LEDOUX, J. E., RUGGIERO, D. A., AND REIS, D. J. Projections to the subcortical forebrain from anatomically defined regions of the medial geniculate
body in the rat. J. Comp. Neurol. 242: 182–213, 1985.
LEDOUX, J. E., SAK AGUCHI, A., IWATA, J., AND REIS, D. J. Interruption of
projections from the medial geniculate body to an archi-neostriatal field
disrupts the classical conditioning of emotional responses to acoustic
stimuli. Neuroscience 17: 615–627, 1986
MC DONALD, A. J. Immunohistochemical identification of gamma-aminobutyric acid containing neurons in the rat basolateral amygdala. Neurosci.
Lett. 53: 203–207, 1985.
MC DONALD, A. J. Cell types and intrinsic connections of the amygdala. In:
The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction, edited by J. P. Aggleton. New York: Wiley-Liss, 1992,
p. 67–96.
MELLO, L.E.A.M., TAN, A. M., AND FINCH, D. M. Convergence of projections from the rat hippocampal formation, medial geniculate and basal
forebrain onto single amygdaloid neurons: an in vivo extra- and intracellular electrophysiological study. Brain Res. 587: 24–40, 1992.
351
352
E. J. LANG AND D. PARÉ
WASHBURN, M. S. AND MOISES, H. C. Inhibitory responses of rat basolateral
amygdaloid neurons recorded in vitro. Neuroscience 50: 811–830, 1992.
WITTER, M. P. AND GROENEWEGEN, H. J. Connections of the parahippocampal cortex in the cat. IV. Subcortical efferents. J. Comp. Neurol. 252:
51–77, 1986.
WITTER, M. P., R OOM, P., G ROENEWEGEN, H. J., AND LOHMAN,
A.H.M. Connections of the parahippocampal cortex in the cat.
V. Intrinsic connections; comments on input / output connections with the hippocampus. J. Comp. Neurol. 252: 78 – 94,
1986.
Downloaded from http://jn.physiology.org/ by 10.220.33.1 on May 2, 2017
/ 9k0b$$ja43
08-13-97 18:02:07
neupal
LP-Neurophys