Functional anatomy of the bed nucleus of the stria terminalis-hypothalamus neural circuitry: Implications for valence surveillance, addiction, feeding, and social behaviors

The bed nucleus of the stria terminalis (BNST) is a medial basal forebrain structure that modulates the hypothalamo-pituitary-adrenal (HPA) axis. The heterogeneous subnuclei of the BNST integrate inputs from mood and reward-related areas and send direct inhibitory projections to the hypothalamus. The connections between the BNST and hypothalamus are conserved across species, promote activation of the HPA axis, and can increase avoidance of aversive environments, which is historically associated with anxiety behaviors. However, BNST-hypothalamus circuitry is also implicated in motivated behaviors, drug seeking, feeding, and sexual behavior. These complex and diverse roles, as well its sexual dimorphism, indicate that the BNST-hypothalamus circuitry is an essential component of the neural circuitry that may underlie various psychiatric diseases, ranging from anorexia to anxiety to addiction. The following review is a cross-species exploration of BNST-hypothalamus circuitry. First, we describe the BNST subnuclei, microcircuitry and complex reciprocal connections with the hypothalamus. We will then discuss the behavioral functions of BNST-hypothalamus circuitry, including valence surveillance, addiction, feeding, and social behavior. Finally, we will address sex differences in morphology and function of the BNST and hypothalamus.