Tuesday, February 17, 2026 2/17/2026

Neural Circuits that Regulate Risk Seeking

Award Number: R01MH110594
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Neural Circuits that Regulate Risk Seeking - Adaptive control of cognitive behaviors in response to changes in uncertainty about future rewards is fundamental for survival. It is not surprising that uncertainty-related maladaptive behaviors, such as maladaptive risk seeking or avoidance, are observed in a wide range of psychiatric disorders. But, to date, the neural mechanisms of uncertainty-mediated risk seeking or risk avoidance are unclear. And, anatomically targeted treatments for many risk-related behavioral states have not been developed. The overarching goal of the current renewal is to uncover the neuronal and behavioral mechanisms of risky decision making under uncertainty. Aim 1 will uncover the mechanisms by which single neurons regulate risky decisions under uncertainty. Our previous work showed that the ventral pallidum (VP) transmits a risk signal before risky decisions. This raised crucial new questions. How does VP compute its risk signal? What is its function in decision making? We hypothesize that VP computes the subjective value of risk in order to govern risk- reward tradeoffs in decision making, and that decision making is controlled by a major recipient of VP projections - the lateral habenula (LhB). Aim 1 will (i) test among leading mechanistic accounts of risky behavior and assess how the subjective value of risk is governed by distinct forms of reward uncertainty and by reward timing, (ii) determine whether VP neurons' activity is necessary and sufficient to control decision making under uncertainty via these mechanisms, and (iii) determine whether and how VP risky decision related activity is reflected in the LHb. Preliminary data indicate that risky decisions arise due to a change in subjective value of risk mediated by uncertainty-sensitive neurons in the VP, and that representations of total subjective value ultimately guide choice through the LhB, downstream of VP. Aim 2 will shed light on the behavioral and neuronal mechanisms through which risk tolerance and value-based decision making are mediated by time. We found that monkeys' behavior closely resembled human decision making: monkeys are more willing to accept risks when they can resolve the resulting uncertainty early instead of having to live with the uncertainty for a prolonged time, and this risk tolerance was reflected in VP and LhB neurons. We hypothesize that timing information that is computationally necessary to control this risk tolerance is encoded in dorsal raphe nucleus (DRN) – a modulatory input to VP and LhB. Aim 2 will (i) characterize how neurons in DRN process the timing- and uncertainty-related variables that govern risk tolerance and (ii) transiently manipulate population activity in the DRN to assess the impact on decisions. Preliminary data show that DRN neurons encode information about time and uncertainty in a manner that is sufficient to control risk tolerance. The Aims offer an unprecedented opportunity to (i) understand the mechanisms of risky decision-making and (ii) study the neuronal activity in brain areas tightly linked to psychiatric disorders that have not been studied in during decision making in the closest animal model to human beings.


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 = $377,075 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Mental Health Research Grants	001	10	1/23/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$377,075
2026	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	9	1/23/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $377,075

Issue Date FY: 2025 ( Subtotal = $393,306 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	9	9/18/2025	NON-COMPETING CONTINUATION	$58,995
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	9	1/14/2025	NON-COMPETING CONTINUATION	$334,311
														Subtotal = $393,306

Issue Date FY: 2024 ( Subtotal = $393,319 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	8	2/5/2024	NON-COMPETING CONTINUATION	$353,987
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	001	8	7/5/2024	NON-COMPETING CONTINUATION	$39,332
														Subtotal = $393,319

Issue Date FY: 2023 ( Subtotal = $397,431 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	7	1/30/2023	NON-COMPETING CONTINUATION	$397,431
														Subtotal = $397,431

Issue Date FY: 2022 ( Subtotal = $403,619 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	6	2/4/2022	COMPETING CONTINUATION	$403,619
2022	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	5	8/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $403,619

Issue Date FY: 2021 ( Subtotal = $381,250 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	5	12/9/2020	NON-COMPETING CONTINUATION	$343,125
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	5	4/7/2021	NON-COMPETING CONTINUATION	$38,125
														Subtotal = $381,250

Issue Date FY: 2020 ( Subtotal = $381,250 )
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	4	12/13/2019	NON-COMPETING CONTINUATION	$343,125
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	4	3/11/2020	NON-COMPETING CONTINUATION	$38,125
														Subtotal = $381,250

Issue Date FY: 2019 ( Subtotal = $381,250 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	3	11/17/2018	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2018 ( Subtotal = $381,250 )
2018	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	2	6/15/2018	NON-COMPETING CONTINUATION	$38,125
2018	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	2	11/7/2017	NON-COMPETING CONTINUATION	$343,125
														Subtotal = $381,250

Issue Date FY: 2017 ( Subtotal = $381,250 )
2017	2017	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	1	2/10/2017	NEW	$381,250
														Subtotal = $381,250

Grand Total All Awards = $3,871,000

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Neural Circuits that Regulate Risk Seeking

Award Number: R01MH110594

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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