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SPLTRAK Abstract Submission
Poster #Other
Potential role of islands of Calleja in regulating grooming and depression-like behavior in mice
Minghong Ma
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

The ventral striatum is a reward center, comprising multiple subdivisions. The islands of Calleja (IC) contain clusters of densely packed granule cells, predominantly situated in the olfactory tubercle (OT). The IC are evolutionally conserved, charaterized by expression of the D3 dopmaine receptor. Optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. As abnormal self-grooming is often observed in mouse models of affective disorders, we invesgiated the potential role of OT D3 neurons in depression-like behavior.  Chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons that project to midbrain dopamine neurons. These studies reveal a crucial role of OT D3 neurons in bidirectionally mediating self-grooming and depression-like behaviors, suggesting a potential therapeutic target.