PV Interneuron Involvement In Social Recognition

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Background and Significance
Social cognition is a complicated process that requires the integration of a wide variety of behaviors, including perception of social signals, reward-seeking, motivation, short-term recognition, and flexible adjustment in social groups. As crucial parts of social cognition, animals, including rodents and primates, have the desire to seek out contact and interaction with conspecifics. This is called social motivation. During this interaction, they need to recognize the behavior of other individuals or the group as a whole, and to respond to social signals appropriately. Social recognition/perception is required for forming long-term attachments, hierarchies, and other complex social strategies critical for survival
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Considerable targeted studies have tried to identify the neural circuitry involved in the social recognition, but the bottom-up strategy (e.g., calcium imaging and electrophysiology) only covers a small region of interest, which limits a whole-brain systematic investigation of PV interneuron involvement in social recognition. The manual staining and analysis of gene expression patterns are labor intensive and difficult to scale up for whole-brain analyses. Other top-down imaging techniques (e.g., MRI) offer only gross macroscale and lack the cellular resolution required for circuit level analysis. Thus, there is a critical need for techniques that allow for brain-wide (system level) analysis while maintaining or even improving spatial (cellular level) resolution. To address this challenge, we and our collaborator applied a novel imaging system, a serial two-photon tomography (STPT) for whole-brain mapping. This method provides us a high-resolution (XY resolution=1 µm) imaging, with a customized data-processing pipeline that is optimized to detect, analyze, and register signals in 3D volumes at a rate of several whole brains per day. Leveraged by transgenic reporter mouse lines expressing GFP under the c-fos promoter, we successfully scaled image analysis to achieve fast, brain-wide activity detection of GFP expression(9). This top-down approach can…show more content…
Recently, we used a bottom-up strategy in a chemogenetics approach, Designer Receptor Exclusively Activated by Designer Drugs (DREADD) to activate PV interneurons in the dentate gyrus and discovered that abnormal activation of PV interneurons impairs social recognition while maintaining normal social motivation (8). To determine the molecular controller for social recognition, β-catenin (β-cat) is a promising candidate as β-cat shapes the excitatory synaptic structure (10, 11) and regulates excitatory postsynaptic strength (12, 13). Interestingly, we found that β-cat knockout (KO) in PV interneurons leads to social recognition deficits, but keeps normal social motivation (14). Our results support that β-cat in PV interneurons is a unique molecular effector that controls social
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