Wednesday, September 17, 2025 9/17/2025

Preclinical Assays of Hippocampal-Prefrontal Cortical Circuit Engagement for Application in Therapeutic Development

Award Number: R01MH126236
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Preclinical Assays of Hippocampal-Prefrontal Cortical Circuit Engagement for Application in Therapeutic Development - TITLE: Preclinical Assays of Hippocampal-Prefrontal Cortical Circuit Engagement for Application in Therapeutic Development FOA type: PAR-19-289: Abstract: The high failure rate of translating discovery science to positive clinical outcomes in the treatment of psychiatric diseases demonstrates the necessity of improving the efficiency and rigor of the therapeutic development pipeline. To this end, the critical importance of advancing the discovery of in vivo physiological and behavioral measures of the engagement of specific circuits for normal cognitive function has been acknowledged across funding initiatives. The hippocampus (HPC)-prefrontal cortical (PFC) circuit is critical for affective processing as well as higher cognitive functions and vulnerable in a number of mental health disorders. Although disrupted functional connectivity in the HPC-PFC circuit is a common feature of anxiety, bipolar disorder, schizophrenia, and autism, how local cellular interactions within this circuit manifest as large-scale temporal coordination to support higher cognitive functions remains unknown. Addressing this fundamental gap in our knowledge will establish a foundation for using circuit-based models for therapeutic target discovery and screening tools of novel drug efficacy. The long-term goal of this proposal, in line with the Funding Opportunity Announcement (PAR-19-289), is to enhance the therapeutic development pipeline for mental illness treatment by optimizing, evaluating, and mechanistically testing neurophysiological and behavioral measures of circuit engagement. The primary objective of this proposal, which is the first step towards achieving our goal, is to relate behavioral performance on the rodent analog on the Paired Associates Learning task (PAL), part of human Cambridge Neuropsychological Test Automated Batteries [CANTAB] assessment, and surface EEG recordings to invasive neurophysiological measures of neural coordination in the HPC-PFC circuit. Through an innovative series of experiments that integrate in vivo neurophysiological local field potential (LFP) recordings, circuit manipulation, surface EEG, and behavior, we will optimize, evaluate and mechanistically test novel noninvasive biomarkers of HPC-PFC circuit engagement by pursuing the following specific aims: 1) Optimize behavioral and non-invasive EEG biomarkers for inferring HPC-PFC circuit engagement and temporal coordination, 2) Evaluation of behavioral and non-invasive EEG biomarkers for determining HPC-PFC circuit engagement through pharmacological manipulation, and 3) Mechanistically test HPC-PFC projections as a driver of surface EEG organization. The proposed research is innovative because it integrates a clinically relevant behavioral task, designed to be analogous to human cognitive assessments, with surface EEG measures that translate across mammals. This will enable the optimization, evaluation, and testing of novel and translatable measures of HPC-PFC circuit engagement in the context of higher cognition and global neural organization. The significance of this contribution will be to provide novel diagnostic tools that can be used to enhance the therapeutic development pipeline for treating mental illness.


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: 2025 ( Subtotal = $657,365 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	5	7/22/2025	NON-COMPETING CONTINUATION	$657,365
2025	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	4	4/24/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	001	4	4/25/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $657,365

Issue Date FY: 2024 ( Subtotal = $790,578 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	3	2/21/2024	SUPPLEMENT FOR EXPANSION	$38,235
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	4	6/17/2024	SUPPLEMENT FOR EXPANSION	$76,469
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	001	4	6/13/2024	NON-COMPETING CONTINUATION	$675,874
														Subtotal = $790,578

Issue Date FY: 2023 ( Subtotal = $624,149 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	3	6/15/2023	NON-COMPETING CONTINUATION	$624,149
														Subtotal = $624,149

Issue Date FY: 2022 ( Subtotal = $674,785 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	2	8/3/2022	NON-COMPETING CONTINUATION	$674,785
														Subtotal = $674,785

Issue Date FY: 2021 ( Subtotal = $727,091 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	1	9/9/2021	NEW	$727,091
														Subtotal = $727,091

Grand Total All Awards = $3,473,968

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Preclinical Assays of Hippocampal-Prefrontal Cortical Circuit Engagement for Application in Therapeutic Development

Award Number: R01MH126236

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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