Neural systems involved in fear and anxiety will be studied using changes in the amplitude of the acoustic startle response, a short-latency reflex that can be elicited in all mammals. Acoustic startle can be increased by presentation of a brief light previously paired with shock (fear-potentiated startle), by sustained exposure to the same light even without prior light-shock pairings (light-enhanced startle), or by intraventricular infusion of corticotropin releasing hormone (CRH-enhanced startle). The PI and colleagues found that lesions or chemical inactivation of the bed nucleus of the stria terminalis (BNST) blocked light-enhanced or CRH-enhanced startle but not fear-potentiated startle. Conversely, lesions or chemical inactivation of the central nucleus of the amygdala blocked fear-potentiated startle but had no effect on light-enhanced or CRH-enhanced startle. The proposed experiments will further characterize similarities and differences between these structures in stress-induced enhancement of the startle reflex. Studies will test whether there is additivity of fear-potentiated startle, light-enhanced startle, and CRH-enhanced startle and whether intraventricular or local infusion into the BNST of the CRH antagonist alpha-helical CRH9-41 will block light-enhanced startle. Induction of c-fos in the amygdala vs. the BNST during presentation of a conditioned fear context vs. an unconditioned anxiogenic context will be measured. Other studies will measure how activation of CRH receptors in the BNST may ultimately increase startle at the level of the brainstem. This will be done by first delineating the neural pathway linking the BNST to the nucleus reticularis pontis caudalis. Previously, these investigators found that if rats were first given extensive overtraining and then given amygdala lesions, relearning could occur with further training. Other studies will evaluate whether the BNST can 'take over' for the amygdala in fear-potentiated startle using lesion, chemical inactivation and IC-fosI methodologies.
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