Synchronous network activity in the maturing prefrontal cortex: mechanistic impact of birth timing and serotonin

University Of Virginia, Charlottesville VA

Investigators

Abstract

PROJECT SUMMARY The brain functionally matures during postnatal windows of heightened plasticity, known as the critical or sensitive periods. While postnatal experience-dependent critical periods depend on inhibitory neurotransmission, the early neonatal critical periods depend on the patterns of intrinsic activity, serotonin signaling and the timing of birth. In sensory areas, intrinsic activity and birth-triggered serotonin signaling support the establishment of sensory maps. However, their roles in the development of frontal areas are unclear. Preliminary studies for this proposal found that the timing of birth drastically impacts intrinsic activity, with reduced synchrony in neonate mice born a day early (preterm mice). Preterm mice have deficits in cognitive function and cortical inhibition, suggesting that birth-triggered neonatal critical period supports the establishment of prefrontal circuits for cognitive function. This proposal uses a combination of in vivo electrophysiology, optogenetics, chemogenetics, confocal imaging, and behavioral assays to mechanistically determine the impact of premature birth and serotonin signaling on prefrontal development, and to test whether postnatal manipulation of intrinsic activity and serotonin can rescue the circuit and behavioral deficits in preterm mice. Through innovative approaches in a novel animal model, this proposal will shed light on the early steps in circuit development whose impairment can increase the risk of atypical neurodevelopment.