Inhibitory Processing and Social Learning in the Mouse Accessory Olfactory Bulb

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Project Summary/Abstract Chemosensory systems contribute extensively to social behavior in humans and other mammals, including mice, a predominant animal model for diseases and disorders that impact human social function. We propose to study the neural circuitry of the accessory olfactory system in order to better understand how this system extracts information from chemical messages and informs social behavior. Without improved understanding of these processes, we risk making mistakes in the interpretation of studies seeking new therapies for diseases and disorders involving social behavior. The activity of excitatory projection neurons called mitral cells (MCs) in the first neural circuit in the accessory olfactory system, called the accessory olfactory bulb (AOB), strongly influences reproductive physiology and social behavior. AOB mitral cell activity is tightly controlled by several types of GABAergic interneurons: juxtaglomerular cells, external granule cells, and internal granule cells (IGCs). We and others have identified that AOB IGCs undergo experience-dependent plasticity following chemosensory social behaviors. We will investigate the hypothesis that these cells, and perhaps other AOB interneurons, are involved in social behavior plasticity. We will use a combination of physiological techniques to investigate cellular and synaptic physiology in AOB interneurons that undergo experience-dependent plasticity. We will study the impacts of interneuron plasticity on chemosensory tuning. We will use targeted viral transgenic strategies to selectively suppress activity of plastic AOB interneurons in vivo and ex vivo while measuring population AOB MC activity using 2-photon calcium imaging and electrophysiological recordings. These experiments will provide mechanistic tests of the hypothesis that experience- dependent plasticity in AOB interneurons suppresses activation by learned, but not unlearned, chemosignals. Finally, we will investigate the impacts of plastic AOB interneurons in social behavior plasticity and brain-wide patterns of neuronal activation during repeated social encounters. Combined, these studies will fill major gaps in our understanding of chemosensory information processing, experience-dependent plasticity, and mammalian social behavior.