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

Award Number: R01MH140184
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2025
PERIOD OF PERFORMANCE END DATE: 01/31/2030

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $392,982 )
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	2	2/9/2026	NON-COMPETING CONTINUATION	$392,982
														Subtotal = $392,982

Issue Date FY: 2025 ( Subtotal = $375,927 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Mental Health Research Grants	000	1	4/18/2025	NEW	$375,927
														Subtotal = $375,927

Grand Total All Awards = $768,909

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

Award Number: R01MH140184

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2025

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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