Neurobiology of Social Behavior: Circuit Analysis in Early Life

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Project Summary My long-termcareer goal is to establish a research laboratory that dissects functional microcircuits supporting flexible social behavior in typical and perturbed development. The lab will integrate state-of-the-art techniques into a large toolkit of convergent methodologies to assess how neural networks exhibit plasticity to support adaptive behavior in early life. To effectively lead this future research team, I require additional professional development and training in techniques for measuring and manipulating neural function in behaving infants. My training to date has provided me with a strong foundation of skills in rodent developmental neurobiology, stress, electrophysiology, optogenetics and ex vivo imaging techniques and a broad theoretical approach. My career development plan expands on this skill set with professional development activities and training in fiber photometry and the use of microdrives to assess neural circuit dynamics during behavior. By engaging in this protected training time, I will enter my independent stage of research well-prepared to lead a research team established to uncover the plasticity of neural circuits supporting social behavior. Research Project: For many species, access to resources requiresa highly flexible system of social behavior that is sensitive to environmental demands. Indeed, inflexible social behavior can be highly maladaptive, particularly during developmental transitions when social demands are in constant flux. Yet, the neural substrates supporting flexible social behavior during development have been underexplored. The literature and pilot data collected for this proposal leads me to advance the central hypothesis that the basolateral amygdala (BLA) and its dopaminergic (DA) control are late-developing components of the social behavior circuit and their recruitment permits behavioral flexibility to transition a system biasing social approach within the nest into one favoring more inhibited approach as infants gain independence and enter the complex socia l world. Specifically, the goal of this BRAIN K99-R00 Award is to apply advanced optical and electrophysiological techniques in infant rats to directly test this hypothesis in three specific aims. Aim 1 will be performed during the mentored phase (K99) and is to determine when in development social approach becomes inhibited and how this is controlled by the BLA. Aim 2, initiated during the mentored phase (K99) and completed duringthe independent phase (R00), is to determine the role of VTA DA release into the BLA in social approach inhibition using convergent approaches to manipulate and measure DA levels in the BLA. Aim 3, performed during the independent phase (R00), will examine the relationship between long-range VTA-BLA synchrony and social approach by optogenetically manipulating DA neurons in the VTA of rats performing a social behavior task while recording spike -LFP synchrony in the VTA and the BLA. Lack of understanding of the developmental neurobiology underlying social behavior disorders impedes our search for effective therapies. By integrating advanced functional techniques into the study of complex infant behavior, the proposed work will advance the field both technically and conceptually.