Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus

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Abstract

The bed nucleus of the stria terminalis (BNST) is believed to be a critical relay between the central nucleus of the amygdala (CE) and the paraventricular nucleus of the hypothalamus in the control of hypothalamic–pituitary–adrenal (HPA) responses elicited by conditioned fear stimuli. If correct, lesions of CE or BNST should block expression of HPA responses elicited by either a specific conditioned fear cue or a conditioned context. To test this, rats were subjected to cued (tone) or contextual classical fear conditioning. Two days later, electrolytic or sham lesions were placed in CE or BNST. After 5 days, the rats were tested for both behavioral (freezing) and neuroendocrine (corticosterone) responses to tone or contextual cues. CE lesions attenuated conditioned freezing and corticosterone responses to both tone and context. In contrast, BNST lesions attenuated these responses to contextual but not tone stimuli. These results suggest CE is indeed an essential output of the amygdala for the expression of conditioned fear responses, including HPA responses, regardless of the nature of the conditioned stimulus. However, because lesions of BNST only affected behavioral and endocrine responses to contextual stimuli, the results do not support the notion that BNST is critical for HPA responses elicited by conditioned fear stimuli in general. Instead, the BNST may be essential specifically for contextual conditioned fear responses, including both behavioral and HPA responses, by virtue of its connections with the hippocampus, a structure essential to contextual conditioning. The results are also not consistent with the hypothesis that BNST is only involved in unconditioned aspects of fear and anxiety.

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Subjects

Adult male Sprague–Dawley rats (Hilltop Laboratories, Scottsdale, PA, USA) weighing 275–325 g at the start of the experiments were used. All animals were acclimated for 2 weeks prior to experimentation. Animals were housed individually in plastic Nalgene cages (Nalge Nunc International, Rochester, NY, USA). The animal colony was on a 12-h light/dark cycle (lights on at 08:00 h) with food and water provided ad libitum. All animals utilized were behaviorally naive. All procedures were conducted

Histological results

Of the 71 CE lesioned animals, 30 met anatomical and histological criteria. Damage to the CE was sustained to its full rostral–caudal extent, and included the lateral CE as well as significant portions of the medial and capsular parts of the CE. The commissural stria terminalis was also damaged in some rats. The borders of the CE lesions were the basal amygdala on the lateral side and the lateral globus pallidus on the medial side, with minimal infringement on either side.

Of the 68 BNST

Discussion

The neural pathways through which emotionally salient environmental events initiate HPA stress hormone responses are poorly understood. In this study, we pursued this issue using classical fear conditioning, a form of emotional stress that has been studied extensively at the neural level. We focused on the role of two structures previously implicated in the activation of the HPA axis by conditioned fear stimuli, the CE and the BNST, and compared the effects of electrolytic lesions of these

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