FUNCTIONAL ROLE OF VTA NEURONAL PROJECTIONS TO THE BNST IN THREAT AND ANXIETY PROCESSING

Anxiety is an adaptive behavioral and physiological response necessary for raising awareness to potential threats in the environment. Understanding the neurobiological mechanisms leading to the pathological maintenance of this response, even in the absence of threat, is critical. The ventral tegmental area (VTA) is central to processing salient stimuli, and beyond coordinating reward experiences, it has been in recent years recognized as a coordinator of defensive behaviors. Activation of different VTA neuronal types is sufficient to trigger a variety of fight or flight responses. The bed nucleus of the stria terminalis (BNST) mediates responses to ambiguous cues in the environment and sits between cognitive and autonomic systems to promote appropriate behavioral strategies. BNST dysfunction may, thus, lead to a sustained state of hypervigilance to unpredictability, a hallmark of anxiety disorders. By combining anatomical, functional, and behavioral approaches, we investigate the functional role of the VTA as an upstream regulator of BNST activity. We hypothesize that VTA neuronal transmission in the BNST promotes heightened attention to salient but ambiguous events, with an exacerbated co-activity generating and maintaining anxious behavior. Our results show that the different VTA neuronal types project to multiple BNST subdivisions, establishing functional connections by exciting BNST cell populations. This VTA terminal excitation in BNST leads to cell-type specific behaviors upon optical manipulation, including rewarding and anxiety-like behaviors. Further exploration of this circuit under naturalistic aversive and anxiety-inducing conditions will enable us to elucidate its role in the development and maintenance of anxiety-like states.