Project Grant F32MH139150

IDENTIFYING A FUNCTIONAL ROLE FOR TRANSCRIPTIONALLY DISTINCT, BLA-ACTIVATED LS ENSEMBLES IN SOCIAL BEHAVIORS - PROJECT SUMMARY SOCIAL RECOGNITION IS THE ABILITY TO DISTINGUISH BETWEEN NOVEL AND FAMILIAR CONSPECIFICS. THIS SOCIAL BEHAVIOR IS ESSENTIAL FOR ORGANISMAL SURVIVAL AS AN ORGANISM MIST BE ABLE TO DIRECT THEIR BEHAVIOR BASED ON A SOCIAL STIMULUS OR PRESENTATION. RECENT EVIDENCE FROM OUR LAB HAS IDENTIFIED THAT NEURONS PROJECTING FROM THE BASOLATERAL AMYGDALA (BLA) TO THE LATERAL SEPTUM (LS) ARE CRITICALLY INVOLVED IN SOCIAL RECOGNITION. HOWEVER, THE MECHANISMS GOVERNING ACTIVATION OF LS NEURONS BY BLA INPUT ARE UNDERSTUDIED. MY LONG-TERM GOAL IS TO BETTER UNDERSTAND THE NEURAL SUBSTRATES REGULATING SOCIAL BEHAVIORS AT THE CIRCUIT, CELLULAR, AND MOLECULAR LEVELS. THE OBJECTIVE OF THIS PROJECT - TO STUDY THE ROLE OF BLA-ACTIVATED LS NEURONAL ENSEMBLES IN REGULATING SOCIAL RECOGNITION, AND TO CHARACTERIZE BOTH THE SPATIAL TOPOGRAPHY AND TRANSCRIPTIONAL HETEROGENEITY OF THESE ENSEMBLES, IS THE FIRST STEP TOWARD THIS LONG-TERM GOAL. BASED ON PREVIOUS FINDINGS IMPLICATING THE BLA-LS CIRCUIT IN REGULATING SOCIAL RECOGNITION, MY CENTRAL HYPOTHESIS IS THAT ACTIVATING LS-PROJECTING BLA NEURONS RECRUITS A TRANSCRIPTIONALLY DISTINCT ENSEMBLE OF LS NEURONS THAT ARE REQUIRED FOR SOCIAL RECOGNITION. THE RATIONALE FOR THE PROPOSED RESEARCH IS THAT IDENTIFYING A FUNCTIONAL ROLE FOR A SPECIFIC, MOLECULARLY DEFINED LS NEURONAL SUBPOPULATION IN SOCIAL RECOGNITION WILL PROVIDE FURTHER UNDERSTANDING OF THE NEURAL SUBSTRATES REGULATING HARDCODED SOCIAL BEHAVIORS ESSENTIAL FOR ORGANISMAL SURVIVAL. THE CENTRAL HYPOTHESIS OF THIS PROPOSAL WILL BE TESTED BY PURSUING TWO SPECIFIC AIMS: 1) ELUCIDATE MOLECULAR SIGNATURES OF BLA-ACTIVATED LS ENSEMBLES ACROSS THE SPATIAL TOPOGRAPHY OF THE LS, AND 2) TEST THE NECESSITY AND SUFFICIENCY OF BLA-ACTIVATED LS NEURONAL ENSEMBLES IN SOCIAL RECOGNITION. THIS APPROACH IS INNOVATIVE BECAUSE IT PROPOSES TO USE CIRCUIT-SPECIFIC, ACTIVITY- DEPENDENT TAGGING OF NEURONAL ENSEMBLES TO BOTH FUNCTIONALLY INTERROGATE THE POPULATION AND COMPREHENSIVELY CHARACTERIZE ITS MOLECULAR SIGNATURE. THE PROPOSED RESEARCH IS SIGNIFICANT BECAUSE IT WILL SHED LIGHT ON THE NEUROBIOLOGICAL UNDERPINNINGS THAT GOVERN THE DEVELOPMENT OF SOCIAL BEHAVIORS, AND COULD POTENTIALLY IDENTIFY NOVEL THERAPEUTIC TARGETS FOR THE TREATMENT OF NEURODEVELOPMENTAL DISORDERS WITH SOCIAL DEFICITS.