Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals

Abstract

The bed nucleus of the stria terminalis (BNST) has been implicated in fear and anxiety, but the specific factors that engage the BNST in defensive behavior are unclear. Here we explore the possibility that ambiguous threats recruit the BNST during Pavlovian fear conditioning in rats. We arranged a conditioned stimulus (CS) to either precede or follow an aversive unconditioned stimulus (US), a procedure that established reliable (forward) or ambiguous (backward) signals for US onset. After conditioning, reversible inactivation of the BNST selectively reduced freezing to the backward CS; BNST inactivation did not affect freezing to the forward CS even when that CS predicted a variable magnitude US. Backward CSs increased Fos in the ventral BNST and in BNST-projecting neurons in the infralimbic cortex, but not the hippocampus or amygdala. These data reveal that BNST circuits process ambiguous threat signals central to the etiology and expression of anxiety.