Regulation of infant social behaviors and learning by the zona incerta - PROJECT SUMMARY Lifelong mental and physical health are seeded during infancy, with parent-infant interactions playing a pivotal role. Despite the critical importance of these early relationships, the neural circuits underlying infant-specific social behaviors remain largely unexplored. This project aims to elucidate these fundamental mechanisms by focusing on a population of somatostatin-expressing neurons in the infant mouse zona incerta (ZISST neurons) that we have identified as crucial for modulating infant responses to maternal presence. Based on our preliminary findings, we posit that ZISST neurons serve as an integrative brain node for the central representation of maternal presence (to be tested in Aim 1), which engages dedicated downstream neural circuits (to be tested in Aim 2) to guide maternal-dependent behavioral responses in the infant (to be tested in Aim 3). Specifically, aim 1 will determine the activity dynamics of ZISST neurons in preweaning mice in response to various maternal behaviors using fiber photometry and single-unit recordings. This will provide detailed insights into how maternal care modulates ZISST neuron activity at both the population and single-cell levels. Aim 2 will establish the functional connectivity of preweaning ZISST neurons and their recruitment by maternal presence through whole-brain mapping and projection-specific recordings. We will perform functional whole-brain mapping of activated (Fos+) neurons in infants under different conditions and use projection-specific expression of jGCaMP7s and fiber photometry to identify circuits that respond to maternal presence. These results will uncover target neural circuits from ZISST neurons that mediate the effects of maternal presence on infant social responses. Finally, aim 3 will leverage newly developed odor learning assays for preweaning mice to test the role of ZISST neurons in mediating the effects of maternal presence on different forms of aversive learning in infants, which rely on diverse sensory and central circuits. By testing the role of ZISST neurons in modulating aversive odor learning using both exteroceptive and interoceptive unconditioned stimuli, this aim will provide critical insights into how ZISST neurons influence learning processes that depend on maternal influence. Utilizing cutting-edge techniques in behavioral analysis, in vivo neural recordings, and neural circuit manipulation, this research will provide a comprehensive understanding of the physiological and anatomical mechanisms by which ZISST neurons mediate infant social behaviors. These insights could inform strategies to enhance early developmental outcomes and mitigate social and developmental disorders, ultimately contributing to improved mental and physical health across the lifespan.
