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Decoding mPFC Plasticity Across Life Stages

Award Number: R21MH143121
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/03/2026
PERIOD OF PERFORMANCE END DATE: 08/02/2028

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Decoding mPFC Plasticity Across Life Stages - The medial prefrontal cortex (mPFC) is a midline cortical region critical for cognition and implicated in neurodevelopmental disorders such as autism spectrum disorders (ASD). Developmental plasticity has been demonstrated in cortical regions associated with sensory function, but much less is known about this in mPFC. Developmental plasticity occurs during critical periods in which plasticity is enhanced, and as such is a period of time in which ongoing experiences shape the ultimate formation of mature functional circuits. Recent evidence suggests an adolescent critical period for mPFC, but the exact timing and underlying synaptic and molecular mechanisms are unclear. To investigate this, we developed a high-throughput assay to test a key form of plasticity, Long Term Potentiation (LTP), in the brain slices of the mouse mPFC. Using multielectrode recording arrays, we record local field potentials and from these extract current-source density (CSD) signals to clearly differentiate pre- and post-synaptic components. Our preliminary data show that while mPFC brain slices from juveniles fail to exhibit LTP, slices from older adolescents have robust LTP, with adult slices showing reduced plasticity. This aligns with the maturation of perineuronal nets (PNNs), specialized extracellular matrices that stabilize circuits by ‘freezing’ plasticity and contributing to mature circuit function. In Aim 1, we will rigorously define mPFC developmental plasticity by mapping LTP and PNN expression across development, which will refine the key time points for complementary in vivo experiments while minimizing animal use. In Aim 2, we will manipulate PNNs and neural activity to test their role in critical period regulation. By degrading PNNs or using Designer Drugs Exclusively Activated by Designer Drugs (DREADDs) to reduce inhibitory activity in the mPFC, we will assess whether the critical period can be reopened in adults. This research integrates high-throughput electrophysiology methods with molecular analyses to uncover mPFC critical periods. Understanding these mechanisms will not only provide insights into prefrontal development but also inform therapeutic strategies for disorders with altered plasticity, such as autism or schizophrenia. 1


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 = $426,991 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research - Research Projects	000	1	8/5/2026	NEW	$426,991
														Subtotal = $426,991

Grand Total All Awards = $426,991

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Decoding mPFC Plasticity Across Life Stages

Award Number: R21MH143121

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/03/2026

PERIOD OF PERFORMANCE END DATE: 08/02/2028

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