Timing of Impulses From the Central Amygdala and Bed Nucleus of the Stria
Terminalis to the Brain Stem
Frank Z. Nagy and Denis Pare ´
Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey
Submitted 19 August 2008; accepted in final form 22 October 2008
Nagy FZ, Pare ´ D. Timing of impulses from the central amygdala
and bed nucleus of the stria terminalis to the brain stem. J
Neurophysiol 100: 3429–3436, 2008. First published October 29,
2008; doi:10.1152/jn.90936.2008. The amygdala and bed nucleus of
the stria terminalis (BNST) are thought to subserve distinct func-
tions, with the former mediating rapid fear responses to discrete
sensory cues and the latter longer “anxiety-like” states in response
to diffuse environmental contingencies. However, these structures
are reciprocally connected and their projection sites overlap ex-
tensively. To shed light on the significance of BNST–amygdala
connections, we compared the antidromic response latencies of
BNST and central amygdala (CE) neurons to brain stem stimula-
tion. Whereas the frequency distribution of latencies was unimodal
in BNST neurons (?10-ms mode), that of CE neurons was bimodal
(?10- and ?30-ms modes). However, after stria terminalis (ST)
lesions, only short-latency antidromic responses were observed,
suggesting that CE axons with long conduction times course
through the ST. Compared with the direct route, the ST greatly
lengthens the path of CE axons to the brain stem, an apparently
disadvantageous arrangement. Because BNST and CE share major
excitatory basolateral amygdala (BL) inputs, lengthening the path
of CE axons might allow synchronization of BNST and CE
impulses to brain stem when activated by BL. To test this, we
applied electrical BL stimuli and compared orthodromic response
latencies in CE and BNST neurons. The latency difference between
CE and BNST neurons to BL stimuli approximated that seen
between the antidromic responses of BNST cells and CE neurons
with long conduction times. These results point to a hitherto
unsuspected level of temporal coordination between the inputs and
outputs of CE and BNST neurons, supporting the idea of shared
I N T R O D U C T I O N
Behavioral findings indicate that the central nucleus of the
amygdala (CE) and bed nuclei of the stria terminalis (BNST)
subserve different functions. In particular, lesion (Campeau
and Davis 1995; Hitchcock and Davis 1987 1991; LeDoux
et al., 1988) and local drug infusion studies (Kim et al. 1993;
Wilensky et al. 2006) have shown that the CE is critically
involved in the rapid expression of conditioned fear responses
to discrete sensory cues, functions that are left intact by BNST
lesions (Gewirtz et al. 1998; LeDoux et al. 1988; Sullivan et al.
2004; Walker and Davis 1997). Instead, BNST lesions interfere
with the development of longer “anxiety-like” states in re-
sponse to more diffuse environmental contingencies, responses
that often persist after termination of the threat (reviewed in
Walker et al. 2003). For instance, BNST lesions were reported
to disrupt corticosterone and freezing responses to contextual
stimuli associated with aversive outcomes (Sullivan et al.
In contrast with these behavioral findings, however, these
two structures exhibit similar anatomical properties. For in-
stance, CE and BNST neurons send robust projections to an
overlapping set of autonomic and motor brain stem nuclei
thought to generate components of fear/anxiety responses
(Dong and Swanson 2004, 2006a–c; Dong et al. 2000; Hol-
stege et al. 1985; Hopkins and Holstege 1978; Veening et al.
1984). Moreover, both receive strong glutamatergic inputs
from the basolateral amygdala (BL) (Dong et al. 2001; Krettek
and Price 1978a,b; Pare et al. 1995; Savender et al. 1995). In
fact, these overlapping connections of CE and BNST, coupled
to similarities in neuronal morphology and transmitter content
(reviewed in McDonald 2003), have led to the proposal that the
BNST and CE constitute one anatomical entity termed the
extended amygdala (Alheid and Heimer 1988; deOlmos and
In further support of this idea, there are strong reciprocal
connections between CE and BNST (Dong and Swanson
2006a-c; Dong et al. 2001; Krettek and Price 1978b; Price
and Amaral 1981; Sun and Cassell 1993; Veinante and
Freund-Mercier 2003). According to these tracing studies,
BNST projections to the CE mostly originate in its antero-
lateral and anteromedial divisions, and the same regions
receive the bulk of CE outputs. A puzzling property of
amygdalo–BNST connections shown in preceding studies is
that there is tremendous heterogeneity in the course taken by
these axons to reach their target. Some follow a direct route,
through and around the substantia innominata (ventral
amygdalofugal pathway). Others follow a circuitous path,
via the stria terminalis, that lengthens their trajectory sev-
eral-fold, raising questions as to the significance of this
peculiar anatomical arrangement.
Thus this study aimed to shed light on the functional signif-
icance of BNST–amygdala connections using extracellular
recordings of BNST and central amygdala (CEA) neurons in
rats anesthetized with isoflurane. Our results point to an unex-
pected level of coordination in the timing of BNST and CE
outputs relative to BL inputs.
M E T H O D S
All procedures were approved by the Institutional Animal Care
and Use committee of Rutgers State University, in compliance with
the Guide for the Care and Use of Laboratory Animals (Depart-
Address for reprint requests and other correspondence: D. Pare ´, CMBN,
Aidekman Research Ctr., Rutgers, The State University of New Jersey, 197
University Ave., Newark, NJ 07102 (E-mail: email@example.com).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
J Neurophysiol 100: 3429–3436, 2008.
First published October 29, 2008; doi:10.1152/jn.90936.2008.
3429 0022-3077/08 $8.00 Copyright © 2008 The American Physiological Society www.jn.org
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3436 F. Z. NAGY AND D. PARE´
J Neurophysiol • VOL 100 • DECEMBER 2008 • www.jn.org