Dealing with aversion: Investigation of the neural substrates for fear and anxiety

The world is a complex and dynamic system, filled with many threats, rewards, and associated cues. To ensure survival, we must deal with incoming threats and cues predictive of threats. Defensive behaviors such as fear and anxiety guide our response to actual and ambiguous threats, respectively. Given their importance to survival, understanding the neural substrates underlying fear and anxiety is paramount but still not complete. With a circuit neuroscience approach, works in my thesis provide evidence that understudied subcortical brain regions such as the lateral Ventral Tegmental Area (VTA) and the Zona Incerta (ZI) contribute to the encoding and modulation of fear and/or anxiety. In the first study, I showed that the lateral VTA gabaergic and glutamatergic neurons encode learned fear. Furthermore, I show that the direct and indirect projections of these lateral VTA subpopulations to the cholinergic interneurons of the dorsal striatum differentially modulate associative fear learning. In my second study, I investigated the ZI and showed that ZI neurons encode cues that contribute to fear learning as well as fear learning itself. In the third and final study, I focused on anxiety and showed that the ZI encode anxiety-related information and actively influence anxiety-like behaviors. Overall, my work advanced our understanding of the neural substrates underlying fear and anxiety.