Effects of lesions of amygdaloid nuclei and substantia nigra on aversive responses induced by electrical stimulation of the inferior colliculus

Stimulation of the central nucleus of the inferior colliculus causes defensive behavior. In this work we examined the influence of lesions of brain structures involved in the expression of fear, such as periaqueductal gray matter, amygdala, and substantia nigra pars reticulata (SNpr), on these aversive responses. Thus, rats were implanted with an electrode in the central nucleus of the inferior colliculus, for the determination of the thresholds of alertness, freezing, and escape responses. Each rat also bore a cannula implanted in the periaqueductal, amygdala or Snpr for injection of the neurotoxin N-methyl-d-aspartate (8 μg/0.8 μl). The data obtained show that lesion of the central nucleus of the amygdala increases the thresholds of aversive responses whereas lesion of the basolateral complex decreases the threshold of these responses. Lesion of the Snpr increased the aversive consequences of the electrical stimulation of the inferior colliculus whereas periaqueductal gray lesions, either dorsal or ventral regions, did not change these responses. From the evidences obtained in this work, it is suggested that the expression of the defensive behavior induced by activation of the neural substrates of the inferior colliculus does not seem to depend on the integrity of the periaqueductal gray. On the contrary, the basolateral complex inhibits and the central nucleus amplifies the aversive responses integrated in the inferior colliculus. Furthermore, SNpr seems also to be an important motor output for the defensive behavior induced by stimulation of the inferior colliculus, in agreement with what has been suggested for other brain structures implicated in the expression of fear.     

Increases in extracellular levels of 5-HT and dopamine in the basolateral, but not in the central, nucleus of amygdala induced by aversive stimulation of the inferior colliculus

Consistent evidence has shown that dopamine release in the prefrontal cortex is increased by electrical stimulation of the inferior colliculus (IC) as unconditioned stimulus. Recent reports have also demonstrated that inactivation of the basolateral nucleus of the amygdala (BLA) with muscimol enhances the behavioural consequences of the aversive stimulation of the IC and reduces the dopamine release in the prefrontal cortex. Moreover, neurotoxic lesions of the BLA enhance whereas those of the central nucleus of the amygdala (CeA) reduce the aversiveness of the electrical stimulation of the IC. Based on these findings the present study examined the effects of the electrical stimulation of the IC on the extracellular levels of serotonin and dopamine in the BLA and CeA. To this end, rats implanted with a stimulation electrode in the IC also bore a microdialysis probe in the BLA or CeA for determination of the release of dopamine and serotonin. IC electrical stimulation at the freezing and escape thresholds increased the levels of serotonin ( approximately 70%) and dopamine ( approximately 60%) in the BLA related to the basal values. Similarly, the metabolites DOPAC and 5-HIAA increased in a parallel fashion in BLA. No significant changes could be detected in these biogenic amines and metabolites in CeA following IC aversive stimulation. These findings point to a differential role of serotonergic and dopaminergic mechanisms of the BLA and CeA in the setting up of adaptive responses to fear states generated at the inferior colliculus level.     

Aversive stimulation of the inferior colliculus changes dopamine and serotonin extracellular levels in the frontal cortex: modulation by the basolateral nucleus of amygdala

We have shown that stimulation of the neural substrates in the inferior colliculus (IC) causes a significant increase in the extracellular levels of dopamine (DA) in frontal cortex (FC). Also, it has been reported that the basolateral complex of the amygdala (BLA) serves as a filter for unconditioned and conditioned aversive information that ascend to higher structures from the brainstem. Linking these two kinds of information, this work examines whether inactivation of BLA interferes with the activation of cortical dopaminergic outputs produced by aversive stimulation of the IC. To this end, rats were implanted with an electrode in the IC for the determination of the threshold of escape responses. Each rat also bore a cannula implanted in the BLA for injections of lidocaine (10 microg/0.5 microL), muscimol (0.5 microg/0.5 microL), or its vehicle and a microdialysis probe in the FC for determination of the amount of DA and serotonin (5-HT). The data obtained show that IC electrical stimulation caused an increase in the DA release while it reduced the 5-HT release in the FC. BLA inactivation with both lidocaine or muscimol enhanced the aversiveness of the electrical stimulation of the IC and attenuated the increase in DA, while the reduction in 5-HT release in the FC remained unaffected. These findings suggest that ascending aversive information from IC on their way up to higher structures in the SNC courses with opposite modulation by DA/5-HT mechanisms in the FC. These processes are regulated by filters located in the BLA. It is proposed that the loss of these BLA regulatory mechanisms prevents the expression of these modulatory mechanisms in the FC that are adaptive responses in order to cope with unconditioned aversive stimulus triggered at the brainstem level.     

The distribution of fos immunoreactivity in rat brain following freezing and escape responses elicited by electrical stimulation of the inferior colliculus

Several sources of evidence indicate that the inferior colliculus also integrates acoustic information of an aversive nature besides its well-known role as a relay station for auditory pathways. Gradual increases of the electrical stimulation of this structure cause in a hierarchical manner alertness, freezing and escape behaviors. Independent groups of animals implanted with bipolar electrodes into the inferior colliculus received electrical stimulation at one of these aversive thresholds. Control animals were submitted to the same procedure but no current was applied. Next, analysis of Fos protein expression was used to map brain areas activated by the inferior colliculus stimulation at each aversive threshold and in the controls. Whereas alertness elicited by stimulation of the inferior colliculus did not cause any significant labeling in any structure studied in relation to the respective control, electrical stimulation applied at the freezing threshold increased Fos-like immunoreactivity in the central amygdaloid nucleus and entorhinal cortex. In contrast, escape response enhanced Fos-like immunoreactivity in the nucleus cuneiform and the dorsal periaqueductal gray matter of the mesencephalon. This evidence supports the notion that freezing and escape behaviors induced by electrical stimulation of the inferior colliculus activate different neural circuitries in the brain. Both defensive behaviors caused significant expression of c-fos in the frontal cortex, hippocampus and basolateral amygdaloid nucleus. This indistinct pattern of c-fos distribution may indicate a more general role for these structures in the modulation of fear-related behaviors. Therefore, the present data bring support to the notion that amygdala, dorsal hippocampus, entorhinal cortex, frontal cortex, dorsal periaqueductal gray matter and cuneiform nucleus altogether play a role in the integration of aversive states generated at the level of the inferior colliculus.     

Differential effects of neurotoxin-induced lesions of the basolateral amygdala and central nucleus of the amygdala on lithium-induced conditioned disgust reactions and conditioned taste avoidance

When rats are intraorally exposed to saccharin solution that has previously been paired with lithium chloride (LiCl), they display Pavlovian conditioned disgust reactions. When exposed to LiCl-paired saccharin solution by bottle, they display suppressed instrumental approach to the bottle resulting in suppressed consumption. The present experiments demonstrated that while neither neurotoxin-induced lesions of the basolateral amygdala (BLA) nor the central nucleus of the amygdala (CeA) attenuated the display of Pavlovian conditioned disgust reactions, lesions of the BLA (but not the CeA) attenuated instrumental conditioned avoidance of the taste. The results are discussed in light of current models of the role of the amygdala in aversive learning.     

Deep brain stimulation in the central nucleus of the amygdala decreases ‘wanting’ and ‘liking’ of food rewards

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever‐pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self‐stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory‐excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an ‘information lesion’ that not only decreased motivational ‘wanting’ of food rewards, but also blocked ‘liking’ of rewards.     

Differential involvement of 5-HT projections within the amygdala in prepulse inhibition but not in psychotomimetic drug-induced hyperlocomotion

While there is abundant evidence for a role of 5-HT and the amygdala in anxiety and depression, the role of 5-HT in this brain region in schizophrenia is less well understood. We therefore examined the effects of local 5-HT depletion in the amygdala on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition, two animal model of aspects of schizophrenia. Pentobarbital-anaesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically micro-injected with 0.5 microl of a 5 microg/mul solution of the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the basolateral (BLA) or central nucleus of amygdala (CeN). Two weeks after the surgery, rats with BLA lesions did not show changes in either psychotomimetic drug-induced locomotor hyperactivity or prepulse inhibition. In contrast, rats with CeN lesions showed significant disruption of prepulse inhibition, but no changes in psychotomimetic drug-induced locomotor hyperactivity. Neurochemical analysis and autoradiographic labelling of 5-HT transporter sites showed that a good degree of anatomical selectivity was obtained. Following administration of 5,7-DHT into the amygdala, the concentration of 5-HT was significantly reduced. Similarly, 5-HT transporter autoradiographs showed differential and selective lesions of 5-HT innervation in targeted subregions of the amygdala. These results provide evidence for differential involvement of 5-HT projections within the amygdala in prepulse inhibition but not locomotor hyperactivity. Thus, the present study supports the view that 5-HT in the amygdala may be involved in aspects of schizophrenia and a target for antipsychotic drug action.     

Exploratory behaviour of rats in the elevated plus-maze is differentially sensitive to inactivation of the basolateral and central amygdaloid nuclei

The amygdala has a crucial role in detecting motivationally significant inputs and in communicating relevant information to other limbic structures. Behavioural studies have shown that the central (CeA) and basolateral (BLA) nuclei of amygdala differentially regulate conditioned and unconditioned fear. Indeed, much evidence has accumulated suggesting that regulatory mechanisms in the BLA serve as a filter for unconditioned and conditioned aversive information that ascends to higher structures from the brainstem, whereas the CeA is the main output for the autonomic and somatic components of fear reaction through major projections to other limbic regions. It is still unclear, however, how amygdaloid nuclei function in high and open spaces so as to determine the characteristic exploratory behaviour of rats submitted to the elevated plus-maze test (EPM). In the present study, we carried out an ethopharmacological analysis of the behaviour of rats submitted to the elevated plus-maze test together with analysis of the tissue content of monoamine dopamine (DA) and serotonin (5-HT) and their metabolites in the dorsal hippocampus (DH), nucleus accumbens (NAC) and dorsal striatum (DS) of animals injected with saline or muscimol (1.0 nmol/0.2 microL) into the BLA or CeA. The data obtained show that injections of muscimol into the CeA, but not into the BLA, caused anxiolytic-like effects in the EPM. Such effects of muscimol into the CeA were accompanied by increases in 5-HT content of the DH, whereas corresponding injections into the BLA caused a reduction in the DA content of the NAC. There was no change in the turnover rates of these monoamines. These data suggest that the BLA and CeA have distinct roles in the exploratory behaviour of rodents in the EPM. While BLA appears to be related to the detection and validation of threatening stimuli, the CeA appears to be involved in the expression of fear behaviours in the EPM.     

Opposing influence of basolateral amygdala and footshock stimulation on neurons of the central amygdala.

BACKGROUND: The basolateral complex (BLA) and the central nucleus of the amygdala (CeA) are believed to mediate the expression of affective responses. After affective learning, conditioned stimulus-related information is thought to be conveyed from the BLA to the CeA; the medial CeA (Cem), in turn, projects to hypothalamic and brainstem structures involved with induction of affective responses. Although the conditioned stimulus and unconditioned stimulus both evoke affective responses, the precise response often differs. It is unknown whether this difference is represented by distinct activity patterns of single Cem neurons. Furthermore, the nature of the interaction between the BLA and Cem is unknown. METHODS: Using in vivo extracellular and intracellular recordings, we examined how the BLA affects the Cem and compared this with effects induced by footshock (unconditioned stimulus) in the same neurons. RESULTS: Our results demonstrate that, contrary to conventional views, BLA stimulation primarily inhibits Cem neurons by a polysynaptic circuit, and show that single Cem neurons respond to both BLA input and footshock in an opposite manner. CONCLUSIONS: These results demonstrate the predominantly inhibitory nature of the BLA-Cem interaction. These data further demonstrate the distinct cellular events that might lead to differential modulation of conditioned and unconditioned affective responses.     

The functional significance of neonatal 5,7-dihydroxytryptamine lesions in the rat: response to selective 5-HT1A and 5-HT2,1C agonists

To study the involvement of serotonin (5-HT) receptor subtypes in behavioral supersensitivity following neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions, we measured acute behavioral responses to a single dose of selective 5-HT1A (8-OH-DPAT) or 5-HT2,1C (DOI) agonist compared to 5-hydroxytryptophan (5-HTP) in rats injected with 5,7-DHT intraperitoneally or intracisternally 14 weeks earlier. Only intraperitoneal 5,7-DHT injection resulted in brainstem 5-HT hyperinnervation, but cortical 5-HT depletions were also less. Effects of DOI, such as shaking behavior and forepaw myoclonus, were enhanced by 5,7-DHT lesions made intracisternally not intraperitoneally, whereas 8-OH-DPAT-evoked behaviors, such as forepaw myoclonus and head weaving, were enhanced more by the intraperitoneal route. The main consequence of intraperitoneal compared to intracisternal 5,7-DHT injection on supersensitivity to 5-HT agonists was increased presynaptic 5-HT1A responses and decreased 5-HT2,1C responses. In contrast, 5-HTP evoked more shaking behavior and less of the serotonin syndrome with the intraperitoneal compared to the intracisternal route of 5,7-DHT injection. Behavioral supersensitivity to 5-HTP, which was attributable to 5-HT1A, 5-HT2,1C, and possibly to other 5-HT receptors, was orders of magnitude greater than that elicited by direct receptor agonists and more clearly differentiated between rats with 5,7-DHT lesions and their controls, and between routes of 5,7-DHT injections, than responses to 5-HT agonists at the dose studied. 5,7-DHT induced dysregulation of 5-HT receptors, including both presynaptic and postsynaptic changes and altered interactions between receptor subtypes, better explains these data than postsynaptic changes alone.     

The effects of acute stress on the regulation of central and basolateral amygdala CRF-binding protein gene expression

Corticotropin-releasing factor (CRF) is a key mediator of the behavioral, autonomic, and endocrine responses to stress. CRF binds two receptors and a CRF-binding protein (CRF-BP), which may inactivate or modulate the actions of CRF at its receptors. The amygdala is an important anatomical substrate for CRF and contains CRF, its receptors, and CRF-BP. Few studies have examined the effects of acute stress on the regulation of amygdala CRF-BP with other CRF system genes. Therefore, we examined the time course of the effects of acute restraint stress on central (CeA) and basolateral (BLA) amygdala CRF system genes. Consistent with our previous study, acute stress increased BLA CRF-BP mRNA shortly after stress offset. Surprisingly, BLA CRF-BP mRNA remained elevated up to 21 h after the stressor. This effect was selective in the BLA as stress did not alter CeA CRF-BP mRNA, and there were no changes in CRF or CRF receptor mRNAs in either amygdala nucleus. These results suggest that alterations in BLA CRF-BP gene expression are a primary response of the BLA/CeA CRF system to acute stress. Because CRF-BP can modulate CRF action, changes in amygdala CRF-BP levels after stress exposure may affect the ability of an organism to adapt to future stressors.     

Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats

Pain is a multidimensional conscious experience including sensory and negative affective components. The neural systems of the sensory component of pain have been extensively studied, while those of the negative affective component are less clear. The amygdala is a forebrain structure composed of several distinct nuclei including the basolateral (BLA) and central (CeA) nuclei, and is thought to be a key neural substrate underlying emotional responses. Recently, we reported that intraplantar (i.pl.) injection of formalin as a chemical somatic noxious stimulus increased c-fos mRNA expression in the BLA, but not CeA, while intraperitoneal (i.p.) injection of acetic acid as a chemical visceral noxious stimulus induced it highly in the CeA, and hardly in BLA [Nakagawa et al. (2003) Neurosci. Lett., 344, 197-200]. In this study, we examined the effects of discrete bilateral excitotoxic lesions of the BLA or CeA on the sensory and negative affective components of the two types of pain in Sprague-Dawley rats. In the place-conditioning paradigm, both i.pl. formalin and i.p. acetic acid produced conditioned place aversion. The i.pl. formalin-induced conditioned place aversion was abolished by the lesion of the BLA or CeA, while the i.p. acetic acid-induced conditioned place aversion was abolished by the CeA-, but not BLA-lesion. On the other hand, the BLA- or CeA-lesion failed to reduce the i.pl. formalin- and i.p. acetic acid-produced nociceptive behaviours. Taken together, these results suggest that activation of distinct amygdaloid nuclei could differentially contribute to chemical somatic and visceral noxious stimuli-induced negative affective, but not sensory components of pains.     

Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan

There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.     

Fos induction in the amygdala by vestibular information during hypergravity stimulation

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness.     

Enhancement of electrically evoked startle-like responses by tetanic stimulation of the superior colliculus

Single-pulse unilateral electrical stimulation of either the amygdala or the inferior colliculus elicited startle-like responses in chloral hydrate anesthetized rats. EMG responses to intracranial stimulation were recorded from the anterior biceps femoris muscles. The EMG responses were generally enhanced following unilateral tetanic stimulation of the deep layers of the superior colliculus, but the enhancement was stronger for amygdala sites than inferior colliculus sites. The enhancement of EMG responses to ipsilateral amygdala stimulation was much larger than that for contralateral amygdala stimulation and that for ipsilateral inferior colliculus stimulation. The enhancement of EMG responses to contralateral inferior colliculus stimulation was not significant. The present study provides a motor-output model for studying plasticity in the neural pathways mediating startle facilitation.     

Amygdala c-Fos induction corresponds to unconditioned and conditioned aversive stimuli but not to freezing

These experiments examined the relationship between freezing and c-Fos expression in the amygdala. In Experiment 1 freezing was elevated during a period immediately following shock in rats that remained in the shock context, but not in rats that were moved to a different, neutral context. The two groups showed equally elevated c-Fos levels in both the central (CeA) and lateral (LA) nuclei. In Experiment 2 rats were shocked in one compartment (paired) and not shocked in another, distinct compartment (unpaired). Rats re-exposed to the paired compartment 24h later froze more than rats exposed to the unpaired compartment, and rats in both groups froze more than un-shocked rats. c-Fos protein expression in CeA, LA and basolateral (BLA) nucleus was elevated in the rats exposed to the paired compartment but not in rats exposed to the unpaired compartment. Thus, c-Fos expression was induced by exposure to both unconditioned and conditioned stimuli, although it is unclear if the same cell population was activated in both cases. Neither case of c-Fos expression coincided with the occurrence of freezing. c-Fos expression may represent neural activity in LA and CeA produced by exposure to unconditioned cues and activity in BLA, LA and CeA produced by conditioned cues. This activity may contribute to an aversive affective state (or "fear"). Behaviors promoted by this state, such as freezing, may be mediated in other brain areas, or by other neurons in the amygdala.     

From aversive associations to defensive programs: experience-dependent synaptic modifications in the central amygdala

Plasticity elicited by fear conditioning (FC) is thought to support the storage of aversive associative memories. Although work over the past decade has revealed FC-induced plasticity beyond canonical sites in the basolateral complex of the amygdala (BLA), it is not known whether modifications across distributed circuits make equivalent or distinct contributions to aversive memory. Here, we review evidence demonstrating that experience-dependent synaptic plasticity in the central nucleus of the amygdala (CeA) has a circumscribed role in memory expression per se, guiding the selection of defensive programs in response to acquired threats. We argue that the CeA may be a key example of a broader phenomenon by which synaptic plasticity at specific nodes of a distributed network makes a complementary contribution to distinct memory processes.     

Regional central serotonin-2 receptor binding and phosphoinositide turnover in rats with 5,7-dihydroxytryptamine lesions

"Denervation supersensitivity" of serotonin (5-HT) receptors has been proposed to explain the behavioral supersensitivity to 5-hydroxytryptophan (5-HTP) which develops after lesions of indoleamine neurons with 5,7-dihydroxytryptamine (5,7-DHT). To examine the possible role of receptor recognition sites and second messenger activity in supersensitivity, we measured regional 5-HT2 receptor ligand binding and 5-HT-stimulated phosphoinositide turnover in adult rats with 5,7-DHT lesions made by intracisternal injection and their saline-treated controls. In [3H]ketanserin binding studies of fresh brain tissue two weeks after 5,7-DHT injection, there were no significant changes in frontal cortex, brainstem, or spinal cord in Bmax, Kd, or nH of 5-HT2 receptors, 5,7-DHT lesions did not affect basal levels of [3H]inositol phosphate (IP) accumulation but significantly increased 5-HT-stimulated [3H]IP accumulation in the brainstem (+27%) and cortex (+23%). Because brainstem rather than cortex is involved in 5-HTP-evoked myoclonus, increased 5-HT-stimulated phosphoinositide hydrolysis in brainstem following 5,7-DHT lesions in the rat may be relevant to serotonergic behavioral supersensitivity.     

Effects of chronic stress on dendritic arborization in the central and extended amygdala

A differential role has been suggested for two important areas in the neural circuitry of stress, central nucleus of the amygdala (CeA) and bed nucleus of stria terminalis (BNST) in the extended amygdala, in regulating fear versus anxiety. Since chronic stress enhances anxiety and consolidation of aversive memories, we examined the effects of chronic immobilization stress (CIS) on neuronal morphology in the CeA and BNST of rats. In contrast to previous reports of stress-induced atrophy in the hippocampus, CIS does not cause dendritic atrophy in CeA and BNST neurons. While dendritic arborization in CeA neurons remains unaffected, it increases in BNST neurons after CIS. These results suggest a role for dendritic remodeling of BNST neurons in stress-induced facilitation of anxiety.