The bed nucleus of the stria terminalis mediates the expression of proactive defensive behavior

Abstract

The bed nucleus of the stria terminalis (BNST) is a forebrain region implicated in aversive responses to uncertain threat. Much of the work on the role of BNST in defensive behavior has used Pavlovian paradigms in which the subject reacts to aversive stimuli delivered in a pattern determined entirely by the experimenter. Here, we report that BNST also mediates proactive defensive responses in a task that allows subjects to prevent the delivery of an aversive outcome. In a standard two-way signaled active avoidance paradigm, male rats learned to shuttle during a tone to avoid shock. Our data demonstrate that chemogenetic inhibition (hM4Di) of BNST attenuates the expression of the avoidance response, whereas chemogenetic activation (hM3Dq) of BNST potentiates the response by extending the period of tone-evoked shuttling. This effect was specific to the BNST, as inactivation of the neighboring medial septum produced no effect on the expression of avoidance. These data support the novel conclusion that BNST mediates two-way avoidance behavior in male rats.