Inhibitory plasticity and social learning in the accessory olfactory bulb

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 multiple physiological techniques to investigate cellular and synaptic physiology in AOB interneurons that undergo experience-dependent plasticity. We will investigate how experience- dependent plasticity modulates interneuron excitability, morphology, and gene transcription. We will determine how interneuron plasticity influences MC chemosensory tuning in vivo and ex vivo using chemogenetics, optogenetics, and live calcium imaging. Finally, we will investigate the impacts of inhibitory plasticity on brain-wide patterns of neuronal activation and social behavior 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.