Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.     

Modulation of the acoustic startle reflex by infusion of corticotropin-releasing hormone into the nucleus reticularis pontis caudalis

The amplitude of the acoustic startle reflex can be modulated by exposure to aversive stimuli or other conditions which evoke a state of fear. The neurotransmitters involved in this modulation are currently being investigated. Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40 and 80 ng) into the nucleus reticularis pontis caudalis (PnC), an obligatory synapse in the acoustic startle reflex, significantly elevated startle amplitude in a dose-dependent manner. The facilitation of startle began immediately following infusion, reached asymptote approximately 20-25 min later, and persisted throughout the remaining 60 min test session. This CRH-enhanced startle effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41, immediately prior to CRH infusion. These results support an involvement of CRH at the level of the PnC in modulating the acoustic startle reflex.     

Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear

The amplitude of the acoustic startle response is reliably enhanced when elicited in the presence of bright light (light-enhanced startle) or in the presence of cues previously paired with shock (fear-potentiated startle). Light-enhanced startle appears to reflect an unconditioned response to an anxiogenic stimulus, whereas fear-potentiated startle reflects a conditioned response to a fear-eliciting stimulus. We examine the involvement of the basolateral nucleus of the amygdala, the central nucleus of the amygdala, and the bed nucleus of the stria terminalis in both phenomena. Immediately before light-enhanced or fear-potentiated startle testing, rats received intracranial infusions of the AMPA receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (3 microg) or PBS. Infusions into the central nucleus of the amygdala blocked fear-potentiated but not light-enhanced startle, and infusions into the bed nucleus of the stria terminalis blocked light-enhanced but not fear-potentiated startle. Infusions into the basolateral amygdala disrupted both phenomena. These findings indicate that the neuroanatomical substrates of fear-potentiated and light-enhanced startle, and perhaps more generally of conditioned and unconditioned fear, may be anatomically dissociated.     

Does the bed nucleus of the stria terminalis mediate fear behaviors?

The bed nucleus of the stria terminalis (BNST) has been implicated in autonomic and hormonal reactions to fearful stimuli, but its role in behavioral reactions to these stressors is less clear. This is puzzling, because 2 closely related areas, the septum and the amygdala, have been repeatedly implicated in fear behaviors. To investigate further, the behavioral effects of BNST lesions were compared to those of septal and amygdaloid lesions in 2 models of rat anxiety: the plus-maze and shock-probe tests. Septal lesions inhibited rats' open-arm avoidance in the plus-maze and suppressed burying of the shock-probe, whereas amygdaloid lesions specifically inhibited shock-probe avoidance. However, BNST lesions produced none of these anti-fear effects; thus, its involvement in the behavioral expression of fear is questionable. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Shock-induced hyperalgesia: III. Role of the bed nucleus of the stria terminalis and amygdaloid nuclei.

Rats exposed to a few moderately intense (1 mA) shocks subsequently exhibit lower vocalization thresholds to shock and thermal stimuli. They also exhibit facilitated learning in a Pavlovian conditioning paradigm. Together, these results suggest that shock exposure can enhance pain (hyperalgesia). The present study examined the role of the amygdala and bed nucleus of the stria terminalis (BNST), 2 systems that have been implicated in the induction and maintenance of negative affective states. Experiment 1 showed that lesions of the central, but not the basolateral, amygdala eliminate shock-induced hyperalgesia as measured by a decrease in vocalization thresholds to shock. Experiment 2 revealed that central nucleus lesions also prevent shock-induced sensitization of the vocalization response to heat. Anterior, but not posterior, BNST lesions had a similar effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions in the anterior bed nucleus of the stria terminalis in Syrian hamsters block short-photoperiod-induced testicular regression

To elucidate the neural circuitry involved in the photoperiodic control of seasonal reproduction, adult male Syrian hamsters, previously housed under long photoperiods (LD; 14 h of light per day), received sham or bilateral radiofrequency-current lesions directed towards one of three anterior-to-posterior levels of the bed nucleus of the stria terminalis (BNST; far anterior, anterior, posterior). They were then transferred to a short photoperiod (SD; 6 h of light per day) for 12 wk, and their testicular weights and plasma FSH, LH, and testosterone concentrations were determined. All of these parameters became markedly inhibited in the sham-lesioned SD controls and also in the far anterior and posterior BNST lesioned groups. In contrast, this inhibitory response to SD was completely abolished in 8 of 14 animals that had received anterior BNST lesions; only in these 8 animals did the lesion encompass the lateral aspect of the anterior BNST. In a second experiment, hamsters that had previously been exposed to SD for 12 wk in order to induce testicular regression were lesioned in the anterior BNST and for the next 4 weeks were either exposed to LD or further maintained in SD. However, in neither case did the anterior BNST lesions perturb the normal photoperiodic response. Paired testes weights and plasma FSH, LH, and testosterone concentrations at 4 wk did not differ significantly (p > 0.05) between the lesioned animals and their respective sham-lesioned LD and SD controls, which, respectively, showed recrudescence of the reproductive axis or remained in a regressed condition. Taken together, the results suggest that lateral aspects of the anterior BNST contain a cell group that is critical for perception of the SD neuro-inhibitory signal; obliteration of this cell group interrupts the transmission of the inhibitory signal to the reproductive axis but does not directly stimulate it.     

The bed nucleus of the stria terminalis is critically involved in enhancing associative learning after stressful experience.

Exposure to an acute stressful event enhances trace eyeblink conditioning in male rats, even when rats begin training days after the stressor (Shors, 2001). The authors examined whether the bed nucleus of the stria terminalis (BNST), an area involved in stress and anxiety, is critically involved in this effect and, if so, when. The authors found that excitotoxic lesions to the BNST prevented the enhanced conditioning after stressor exposure. In addition, temporary inactivation of the BNST during the stressor did not alter enhanced responding, whereas inactivation during training prevented the enhancement. These data indicate that stressful experience induces persistent changes in the BNST that are necessary for enhancing learning well after the stressful event has ceased. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of lesions in the amygdala, periamygdaloid cortex, and stria terminalis on aggressive behaviors in rats.

In 3 experiments, with a total of 113 male albino Sprague-Dawley rats, it was found that small lesions in the periamygdaloid cortex, cortical amygdaloid nucleus, or bed nuclei of the stria terminalis reduced or eliminated attacks and signs of dominance in fights which were generated by isolated housing and the omission of food reward. The same lesions had little or no effect on pain-induced or reflexive "fighting" or on mouse-killing. Small lesions in the lateral or central amygdaloid nuclei significantly inhibited pain-induced "aggression," but did not modify attack behavior or dominance in fights that occurred in situations not involving painful stimulation. These lesions also did not alter mouse-killing behavior. Results suggest that the periamygdaloid cortex and cortical amygdaloid nucleus, as well as the stria terminalis, may be part of a neural system which influences intraspecies aggression in male rats. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions of the bed nucleus of the stria terminalis, lateral hypothalamus, or insular cortex on conditioned taste aversion and conditioned odor aversion.

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of a sexually dimorphic projection from the bed nuclei of the stria terminalis to the anteroventral periventricular nucleus in the rat

The principal nucleus of the bed nuclei of the stria terminalis (BSTp) is larger in male rats and conveys olfactory information relevant for reproduction to the hypothalamus. In males, the BSTp provides a massive projection to the anteroventral periventricular nucleus of the preoptic region (AVPV), which in contrast to most sexually dimorphic nuclei contains more neurons in female rats. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the BSTp of adult female rats failed to demonstrate the strong projection to the AVPV observed previously in males. The ontogeny of this robust sex difference was examined by using the axonal marker DiI. The projection from the BSTp to the AVPV is established between postnatal day 9 (P9) and P10 in male rats and seems to be maintained during the juvenile period. Although labeled fibers extended from the BSTp toward the preoptic region in both male and female neonates, a similar connection with the AVPV was not apparent in female rats at any of the ages studied, and the density of labeled axons in the AVPV of P10 males was 20-fold greater than that of P10 females. A projection from the BSTp to the medial preoptic nucleus was also weaker in females but was much more substantial than that to the AVPV. These findings suggest that a sex- and region-specific activity influences the development of the projection from the BSTp to the AVPV, producing a sexually dimorphic architecture in pathways that convey olfactory information to the hypothalamus.     

Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats.

Attempts to condition fear potentiation of startle (FPS) in rats younger than 23 days of age have not been successful, regardless of the type of aversively conditioned stimulus used (P. S. Hunt, R. Richardson, & B. A. Campbell, 1994; R. Richardson, G. Paxinos, & J. Lee, 2000; R. Richardson & A. Vishney, 2000). In the present study, the authors report that peripheral injections of strychnine hydrochloride, a glycine receptor antagonist, and intracerebroventricular infusions of corticotropin releasing hormone (CRH) both potentiated the acoustic startle response (ASR) in 16–18-day-old rats. Because strychnine and CRH have distinct sites of activation in the primary startle pathway, it can be concluded that this pathway is functional and modifiable in rats younger than 23 days of age. This finding suggests that the failure to observe conditioned FPS in preweanling rats is due to an immaturity of the secondary fear circuit responsible for enhancing the ASR during a fear state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal integration in the acoustic startle reflex of the rat.

Exposed 6 male albino rats to 6,900 Hz tone pulses with durations of .25-64 msec. and intensities of 80-125 db. re .0002 dyne/cm2. Startle amplitudes increased with duration in a manner suggestive of an exponential function distorted by the failure of the auditory system to reflect faithfully prolonged intense sounds. 5 other male albino rats were exposed to pairs of 1-msec pulses at 125 db., having interpulse intervals ranging 1-11 msec. For pulses separated by 3 msec. or more, response amplitudes demonstrated a decaying exponential summation function with a time constant of 3 msec. Results are in accord with established principles of reflex function and organization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid stress-induced elevations in corticotropin-releasing hormone mRNA in rat central amygdala nucleus and hypothalamic paraventricular nucleus: an in situ hybridization analysis

High densities of nerve cells containing corticotropin-releasing hormone (CRH) are located in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) of the hypothalamus. These brain regions play an important role in activating autonomic, behavioral, and endocrine responses to stress. This study was conducted to provide needed information concerning the acute effects of stress on CeA and PVN CRH mRNA expression. Rats were exposed to restraint stress for 1 h and brains collected after a 1-h post-stress interval. CRH mRNA expression occurring in the CeA and PVN was examined using in situ hybridization techniques. Densitometric analysis revealed that acute restraint stress produced significant increases in CRH mRNA levels in the PVN and in the rostral CeA region. In addition, the area in the rostral CeA encompassing high CRH mRNA signals increased significantly after stress. Results provide clear evidence that CRH neurons in the CeA and PVN exhibit rapid increases in CRH mRNA expression after exposure to stress.     

Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: Aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear.

Four experiments investigated the effects of lesions of the bed nucleus of the stria terminalis (BNST) on conditioned fear and anxiety. Though BNST lesions did not disrupt fear conditioning with a short-duration conditional stimulus (CS; Experiments 1 and 3), the lesion attenuated conditioning with a longer duration CS (Experiments 1 and 2). Experiment 3 found that lesions attenuated reinstatement of extinguished fear, which relies on contextual conditioning. Experiment 4 confirmed that the lesion reduced unconditioned anxiety in an elevated zero maze. The authors suggest that long-duration CSs, whether explicit cues or contexts, evoke anxiety conditioned responses, which are dissociable from fear responses to shorter CSs. Results are consistent with behavioral and anatomical distinctions between fear and anxiety and with a behavior-systems view of defensive conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Corticotropin-releasing factor type II (CRF?) receptors in the bed nucleus of the stria terminalis modulate conditioned defeat in Syrian hamsters (Mesocricetus auratus).

In Syrian hamsters (Mesocricetus auratus), social defeat produces a subsequent increase in submissive and defensive behavior and a loss of normal territorial aggression, which the authors have called conditioned defeat. In this study, the authors investigated the effect of blocking corticotropin-releasing factor (CRF) Type I and Type II receptors on conditioned defeat. Intracerebroventricular infusion of the CRF? receptor antagonist antisauvagine-30 prior to testing significantly reduced conditioned defeat compared with vehicle controls, whereas the CRF? receptor antagonist CP-154,526 had no effect. Also, infusion of antisauvagine-30 into the bed nucleus of the stria terminalis (BNST) 15 min, but not immediately, prior to testing reduced conditioned defeat in a dose-dependent manner. The authors' results provide evidence that CRF? receptors in the BNST, but not CRF? receptors, are an important component in the neural circuitry regulating conditioned defeat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reflex-inhibiting stimuli and the refractory period of the acoustic startle reflex in the rat.

Previous studies show that if acoustic startle stimuli are presented in pairs, then the reaction to the 2nd stimulus (S2) is reduced, with the size of the refractory decrement determined by the interstimulus interval and the relative intensity of the 1st stimulus (S1). If a neutral stimulus (p) is presented just prior to S1, then the reaction to S1 is similarly inhibited, revealing the phenomenon of prestimulus inhibition. In 2 experiments with male albino Holtzman rats (N = 24) it was found that suppression of the reflex to S2 by S1 was unaffected by prestimulus inhibition of S1 (i.e., reflex amplitudes associated with S2 were identical in pS1-S2 series and S1-S2 series). In contrast, a reduction in the intensity of S1 relative to S2 did reduce the effect of S1 on S2. These data indicate that prestimulus inhibition of the reflex to S1 does not result because the preliminary stimulus attenuates the sensory impact of S1. The inhibitory process may be presumed to have a central locus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spectral frequency and the modulation of the acoustic startle reflex by background noise.

The rat's (Long-Evans) acoustic startle reflex to a high-frequency tone burst (10.5 kHz) was depressed by intense high-frequency band-pass noise (8–26 kHz) but enhanced by low frequency noise (1–2 kHz). However, contrary to the hypothesis that the depression of startle in intense background noise is produced by sensory masking, the reflex to a low-freqency tone burst (at 1 kHz) was depressed by both high- and low-frequency band-pass noise. Two additional hypotheses are offered to supplement sensory masking in order to explain the asymmetry in these data. The first is that the intratympanic reflex, which acts as a high pass filter on acoustic input, is elicited in intense backgrounds. The second is that acoustic startle reflexes elicited by intense low-frequency tones are in part elicited by their high-frequency distortion products and that these distortion products are then masked by high-frequency background noise. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Importance of pup-related sensory inputs and maternal performance for the expression of Fos-like immunoreactivity in the preoptic area and ventral bed nucleus of the stria terminalis of postpartum rats.

This study used Fos immunocytochemistry to locate neurons within the medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBNST) that are tightly associated with the performance of maternal behavior in postpartum rats. In the 1st experiment, a high degree of Fos activation was observed in these regions if females were allowed to interact fully with pups, but not if they could receive only olfactory, visual, and auditory inputs from pups. The 2nd experiment found that olfactory bulbectomy combined with thelectomy did not eliminate Fos expression in the MPOA and VBNST of females displaying maternal behavior. These Fos-expressing neurons may represent efferent neurons essential for the performance of maternal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Species differences in the vasopressin-immunoreactive pathways in the bed nucleus of the stria terminalis and medial amygdaloid nucleus in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus).

Vasopressin-immunoreactive (AVP-ir) cells in the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MAN) and their AVP-ir projections to the lateral septum were studied in monogamous prairie voles (Microtus ochrogaster) and promiscuous meadow voles (M. pennsylvanicus). A sexually dimorphic AVP-ir pathway was found in both species; males had more AVP-ir cells in the BST and MAN, as well as denser AVP-ir fibers in the lateral septum, than did females. A significant species difference was also found. Overall, meadow voles had more AVP-ir cells in the BST and MAN than did prairie voles. Male prairie voles, however, had a higher density of AVP-ir fibers in the lateral septum than male meadow voles. The species difference in the sexually dimorphic AVP-ir projections in the BST and MAN is implicated in the rodents' different life strategy and behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transections of stria medullaris or stria terminalis in the rat: Effects on aversively controlled behavior.

Surgical transection of the stria medullaris (SM) in male albino rats reliably interfered with the acquisition of a 1-way avoidance response but had no effect on 2-way shuttlebox avoidance, passive avoidance, intake of palatable fluids, or locomotor activity. Transection of the stria terminalis (ST) selectively interfered with Ss' reactions to punishments in a passive avoidance situation but had no effect on 1-way or 2-way active avoidance or on locomotor activity. This pattern of effects complements the results of earlier investigations that showed that 2-way avoidance learning (but not 1-way avoidance or passive avoidance behavior) was impaired after fornicotomy and after transection of the ventral connections of the septum with the lower brainstem. The latter cut, but not fornicotomy or transection of ST or SM, reproduced the effects of septal lesions on water intake, body weight, and preferential intake of palatable solutions. Results support the hypothesis that the septum exercises a number of separate functions that are mediated by different pathways. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)