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Prefrontal CRF and the Regulation of Goal Directed Behavior

Award Number: R01MH116526
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/05/2018
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Prefrontal CRF and the Regulation of Goal Directed Behavior - Project Summary The prefrontal cortex (PFC) supports a constellation of ‘executive’ cognitive processes that guide goal-directed behavior. Dysregulation of PFC-dependent cognition is associated with numerous behavioral disorders. Currently there is a strong need for improved treatments for PFC- dependent cognitive dysfunction. However, the development of novel treatments is hindered by our limited understanding of the neurobiology underlying PFC-dependent cognition. In recent studies we demonstrated that corticotropin-releasing factor (CRF) neurons in the caudal, but not rostral, dorsomedial PFC (dmPFC) of male and female rats (outside proestrus) impair two distinct cognitive processes: working memory and sustained attention. Conversely, inhibition of PFC CRF neuronal activity or blockade of CRF receptors, locally or globally in the brain, improved PFC- dependent cognition. Interestingly, the regulatory actions of CRF across these distinct cognitive processes involve distinct pathways: local release for working memory and extra-PFC release for sustained attention. The mediodorsal nucleus of the thalamus (MDthal) plays a central role in the regulation of PFC-dependent function. Preliminary studies indicate that MDthal plays a prominent role in the sustained attention actions of PFC CRF neurons. We recently demonstrated that the PFC CRF neurons are comprised of both glutamatergic (CRFGlu, 85%) and GABAergic (CRFGABA, 15%) subpopulations. The proposed multidisciplinary studies will provide a better understanding of neural mechanisms that underlie the cognitive actions of PFC CRF neurons. Aim 1 uses recently developed viral vector-based chemogenetic manipulations to determine the cognitive actions of CRFGlu and CRFGABA neurons. Aim 2, building on preliminary observations tests the hypothesis that the sustained attention (an possibly working memory) actions of PFC CRF neurons involve projections to the MDthal. Aim 3 examines the neural coding actions of caudal dmPFC CRFGlu and CRFGABA across the PFC-MDthal circuit. Collectively, these studies will provide novel insight into the neurobiology of PFC-dependent cognition. In doing so, these studies may provide a better understanding of the neural bases of PFC cognitive dysfunction and lead to novel treatment strategies for PFC-dependent cognitive dysfunction.


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 = $614,581 )
2026	2026	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	9	12/9/2025	NON-COMPETING CONTINUATION	$614,581
														Subtotal = $614,581

Issue Date FY: 2025 ( Subtotal = $614,581 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	8	1/3/2025	NON-COMPETING CONTINUATION	$522,394
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	001	8	8/14/2025	NON-COMPETING CONTINUATION	$92,187
														Subtotal = $614,581

Issue Date FY: 2024 ( Subtotal = $614,581 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	003	7	7/5/2024	NON-COMPETING CONTINUATION	$61,458
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	7	12/6/2023	NON-COMPETING CONTINUATION	$553,123
2024	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	002	6	12/11/2023	COMPETING CONTINUATION	$136,283
2024	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	001	5	12/11/2023	NON-COMPETING CONTINUATION	-$136,283
														Subtotal = $614,581

Issue Date FY: 2023 ( Subtotal = $614,581 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	6	1/18/2023	COMPETING CONTINUATION	$614,581
														Subtotal = $614,581

Issue Date FY: 2022 ( Subtotal = $470,549 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	001	5	5/16/2022	NON-COMPETING CONTINUATION	$47,056
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	5	1/18/2022	NON-COMPETING CONTINUATION	$423,493
														Subtotal = $470,549

Issue Date FY: 2021 ( Subtotal = $470,549 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	4	1/26/2021	NON-COMPETING CONTINUATION	$470,549
														Subtotal = $470,549

Issue Date FY: 2020 ( Subtotal = $470,549 )
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	3	1/22/2020	NON-COMPETING CONTINUATION	$470,549
														Subtotal = $470,549

Issue Date FY: 2019 ( Subtotal = $470,549 )
2019	2019	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	2	12/19/2018	NON-COMPETING CONTINUATION	$470,549
														Subtotal = $470,549

Issue Date FY: 2018 ( Subtotal = $445,240 )
2018	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Mental Health Research Grants	000	1	3/5/2018	NEW	$445,240
														Subtotal = $445,240

Grand Total All Awards = $4,785,760

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Prefrontal CRF and the Regulation of Goal Directed Behavior

Award Number: R01MH116526

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/05/2018

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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