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175 | Early-life stress modulates the development of prefrontal-raphe circuits and stress-responses of serotonin neurons

Neural Circuits and Systems Neuroscience

Author: Carla Veronica Argañaraz | email: carlavarganaraz@gmail.com


Carla Veronica Argañaraz , Mariano Soiza Reilly

1° Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) – Universidad de Buenos Aires, Argentina.

Early adversity represents a main risk factor for the emergence of psychiatric disorders in adult life. In mice, the stress of maternal separation (MS) during postnatal days (P) 2 to 14 produces anxiety and depressive-like phenotypes in adult life. We found that MS during this period alters the maturation of prefrontal circuits, producing a hyperinnervation of the prefrontal cortex (PFC) to dorsal raphe nucleus (DRN) synaptic circuit. This pathway is crucially involved in stress-coping strategies in response to uncontrollable stress and mood control by modulating serotonin (5-HT) release from DRN neurons. However, whether such changes in synaptic innervation could modify the stress-response of DRN 5-HT neurons that may contribute to adult emotional alterations remains unexplored. To tackle this, we assessed the early activation (at P15) of DRN 5-HT neurons in maternally-separated mice in response to a swim stress known to engage the PFC-to-DRN circuit. Our study involved a behavioral challenge in the forced swim test (FST) and c-Fos/5-HT immunofluorescent labeling in the DRN. These investigations will contribute to expand the current understanding of how early-life stress can influence the activity of developing 5-HT networks.