209 | Early-life stress shapes developing prefrontal to dorsal raphe circuit

Neural Circuits and Systems Neuroscience

Author: Carla Veronica Argañaraz | Email: carganaraz@fbmc.fcen.uba.ar

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-life experience can influence neural circuit development. Although this can help an individual to adapt to environmental conditions, it can also lead to maladaptive circuit alterations that could increase the adult vulnerability to develop psychiatric disorders. The stress of maternal separation (MS) in mice during a critical period of ages (between postnatal days (P) 2 to 14) represents a well-established model of how early-life stress alters the adult emotional control with the appearance of anxiety and depressive-like symptoms. We propose that this critical period is a crucial neurodevelopmental window for the maturation of emotional circuits such as the one connecting the prefrontal cortex (PFC) to the dorsal raphe nucleus (DRN). We found that MS increases the PFC synaptic innervation of the DRN, a nucleus known for harboring most of the serotonin (5-HT)-producing neurons, a neurotransmitter key in stress-coping and mood regulation. MS-exposed mice concomitantly show an early enhancement of 5-HT neuron activity in response to stress, suggesting functional changes in the PFC-DRN circuit. Preliminary results indicate that the early activity of PFC glutamate projection neurons engaged in the PFC-DRN circuit could be selectively affected by early-life stress. Our study contributes to the understanding on how early-life adversity impacts on neurodevelopment of mood and emotional brain circuits.