The ability to detect and appropriately respond to potentially threatening situations is critical for survival. Dysregulation of the neural systems which mediate these functions can lead to pathological avoidance of ordinary environments and persistent feelings of imminent threat, key components of the negative emotional state characteristic of anxiety disorders. Many studies have begun to reveal the brain regions and neural circuits that control avoidance behavior and encode states of anxiety. Specifically, the ventral hippocampus has emerged as a critical node for emotional behaviors including those evoked by anxiogenic environments. Our lab and others have found that subpopulations of single neurons in ventral CA1 are activated by aversive environments, but this selectivity does not generalize across different tasks used to assay anxiety-like behavior. Moreover, it is unclear which inputs to the ventral hippocampus provide the emotional information that drives this anxiety-related neural activity. The mechanism by which the ventral hippocampus encodes anxiety states is still unknown and investigating how this brain region represents these emotional states is an essential step towards understanding the neural substrates of anxiety disorders. In this proposal, I will utilize pose estimation algorithms and unsupervised behavioral segmentation (Aim 1), in vivo calcium imaging and neural population analyses (Aim 2), along with simultaneous input-specific optogenetic inhibition and calcium imaging (Aim 3) to characterize the behavioral manifestations of anxiety-like emotional states and determine how they are encoded in the ventral hippocampus. Successful completion of this study will help to elucidate the role of the ventral hippocampus in anxiety, potentially opening new research avenues for the development of neural circuit based therapeutics to treat anxiety disorders. These data along with the research and scientific expertise developed through this Kirschstein-NRSA F30 Fellowship Award will support my long-term goal of becoming an independent physician-scientist.
Anxiety is characterized by a persistent and disruptive negative emotional state. This proposal will utilize pose estimation algorithms, unsupervised behavioral segmentation, neural population analyses, and simultaneous in vivo calcium imaging and input-specific optogenetic inhibition to investigate the mechanism by which the ventral hippocampus encodes anxiety-like emotional states. Determining the neural substrates of anxiety will uncover novel avenues of research for the development of neural circuit based therapeutics to treat anxiety disorders.
