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CELLULAR AND SYNAPTIC DISSECTION OF THE NEURONAL CIRCUITS OF SOCIAL AND AUTISTIC BEHAVIOR

Final Report Summary - CELLSYNCIRCUITS (CELLULAR AND SYNAPTIC DISSECTION OF THE NEURONAL CIRCUITS OF SOCIAL AND AUTISTIC BEHAVIOR)

Synapses are cellular specializations responsible for transducing information between neurons. Dysfunction at these structures impairs the normal function of neuronal circuits and may underlie disorders such as schizophrenia and autism. Not only in these disorders, but in various types of neuropsychiatric afflictions one of the most prominent dysfunction is in social behaviors. At the same time, isolation from social interactions or stressful social environment may itself trigger mental disorders. Nevertheless, the precise synaptic circuits and pathways that regulate the expression of various types of social behaviors are still largely unexplored. Thus, it remains critically important to identify and understand the neuronal synaptic circuits regulating the “social brain”.

We are particularly interested in understanding the circuits that inform on social recognition, social rank and social dominance. These tasks are deployed daily by most social species in the recognition and identification of a social hierarchy. Ranked hierarchy, or in the simplest cases, a “pecking order”, are common occurrence in nature that are thought to promote an equilibrium between the sharing of resources and the minimization of violent intragroup conflict. At the most basic level, stable hierarchies determine preferential access to food, mating partners and the choice for nesting place. At the neurobiological level, the medial prefrontal cortex has been shown to be implicated in the regulation of social hierarchy from rodents to primates, however, little else is known of the genes and synaptic circuits regulating these processes.
Specifically, we want to understand what are the molecular determinants predicting or influencing dominant and subordinate behavior. What are the neural pathways downstream of the computations occurring in the prefrontal cortex and how is “social rank” coded in the brain?

We have focused on the genetic and environmental triggers that manipulate the propensity for more dominant or submissive behavior in social hierarchies, with support from Marie Curie Actions we discovered that early life deprivation and adversity (EDA) triggers a form of stress for which the end result is not only an epigenetic alteration in gene expression but also perturbed behavioral strategies in social interactions that result in critical alterations to social hierarchies.
Our research as allowed us to:
1. Identify several genes as potential regulators/markers for social dominance by performing a detailed characterization of EDA mice using next generation sequencing (RNA-Seq).
2. Identify neuronal morphology changes in prefrontal brain regions linked to EDA and social subordinate phenotype.
3. Discover alterations in synaptic signaling across cortical microcircuits in subordinate mice.
4. Modulated social hierarchies by manipulating prefrontal cortical network activity using optogenetics.
5. Created a strategy to perform cortico-striatal recording in the context of hierarchical social encounters.


The Marie Curie CIG awarded to João Peça has allowed us to make strides in understanding the cellular and circuits regulating social behaviors.