Extended amygdala circuits are differentially activated by context fear conditioning in male and female rats

Abstract

As the incidence of anxiety disorders is more prevalent in females, comparing the neural underpinnings of anxiety in males and females is imperative. The bed nucleus of the stria terminalis (BNST) contributes to long-lasting, anxiety-like states including the expression of context fear conditioning. Currently, there is conflicting evidence as to which nuclei of the BNST contribute to these behaviors. The anterolateral portion of the BNST (BNST-AL) located dorsal to the anterior commissure and lateral to the stria terminalis sends robust projections to the central nucleus of the amygdala (CE). Here we asked whether the BNST-AL is active during the expression of context fear conditioning in both male and female rats. At the cellular level, the expression of context fear produced upregulation of the immediate-early gene ARC in the BNST-AL as well as an upregulation of ARC specifically in neurons projecting to the CE, as labeled by the retrograde tracer Fluorogold infused into the CE. However, this pattern of ARC expression was observed in male rats only. Excitotoxic lesions of the BNST reduced context fear expression in both sexes, suggesting that a different set of BNST subnuclei may be recruited by the expression of fear and anxiety-like behaviors in females. Overall, our data highlight the involvement of the BNST-AL in fear expression in males, and suggest that subnuclei of the BNST may be functionally different in male and female rats.

Keywords: ARC; Amygdala; Anxiety; BNST; Fear conditioning.