Neurobiology of Social Behavior: Circuit Analysis in Early Life

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Project Summary For many species, access to resources requires a 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 lead us 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 social world. Specifically, the goal of the parent BRAIN R00 Award is to apply advanced optical and electrophysiological techniques in infant rats to directly test this hypothesis in two specific aims. Aim 1 is to determine how adversity impacts electrophysiological signaling in the basolateral amygdala. Aim 2 will assess real-time dynamics of dopamine signaling within the BLA in typical and perturbed development. Aim 3 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. To pursue these Aims, we are requesting this supplement to support the training and career development of a postdoctoral researcher, Dr. Cesar Medina. Dr. Medina is a Latino U.S. citizen. He will be working as a postdoctoral fellow in my lab to model adversity and collect neurobehavioral measures during rat pup social behavior at these two ages. In support of Aim 2 of the parent R00 grant, Dr. Medina will employ virus-mediated strategies to measure the activity of biosensors for dopamine in the basolateral amygdala using fiber photometry. In support of Aim 3, Dr. Medina will record from multiple brain areas simultaneously and assess measures of functional coupling between spikes and oscillations (local field potentials, LFP), including synchrony, coherence, power, directional entrainment, and phase-phase coupling. During the proposed support period, Dr. Medina will receive training in technical skills and career development from Dr. Maya Opendak and Dr. Jeremiah Cohen. This training and mentorship will be structured to support Dr. Medina’s goal of leading an independent research team studying the neural circuitry supporting complex behavior and how it is impacted by adversity.