Top‐Down Control of Isolation‐Induced Aggression Through mPFC Tac2+ Interneurons

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Project Summary/Abstract As social creatures, social interaction is vital for mammalian health. Prolonged separation from social environments can result in social isolation stress, which is linked to poor mental health outcomes, including anxiety, depression, and violence. Despite this, relatively little is known about the neurobiology underlying these changes induced by social isolation, representing a critical gap in the field. In this proposal, I will investigate the role of Tachykinin 2-expressing (Tac2+) interneurons in the medial prefrontal cortex (mPFC) in regulating isolation-induced aggression, through a combination of genetic characterization, cell-type specific functional manipulations, and in vivo imaging approaches. My preliminary work establishes mPFC Tac2+ neurons as interneurons and finds isolation-induced aggression in both male and female mice. In Aim 1 I will use an in situ hybridization assay to investigate the extent to which neuropeptide-encoding genes are expressed in mPFC Tac2+ interneurons to understand whether these neurons are a homogenous population or can be subdivided into subpopulations. Then, in Aim 2 I will examine whether the activity of mPFC Tac2+ interneurons or Tac2/Neurokinin B signaling is necessary for isolation-aggression and will investigate the role of neurokinin B in this process. Lastly in Aim 3, I will use dual-color in vivo microendoscopic imaging of different colored calcium indicators expressed in mPFC Tac2+ interneurons and mPFC pyramidal neurons, respectively, to understand the activity of these neuronal populations during isolation-induced aggression. This project builds off my strong background in rodent behavior and allows me to gain computational skills for the analysis of behavior and calcium imaging data. Under the training provided by this fellowship, I will gain the necessary technical skills, knowledge of my field, and data analysis skills to assist in my transition to a postdoctoral position in systems neuroscience and achieve my career goal of becoming a professor at a research-intensive institution. Through understanding the contribution of mPFC Tac2+ interneurons to isolation-induced aggression, this project will further our understanding of the circuit-level mechanisms that contribute to mental health issues resulting from prolonged social isolation.