# Neural Circuits that Regulate Risk Seeking

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $403,619

## Abstract

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 n...

## Key facts

- **NIH application ID:** 10298264
- **Project number:** 2R01MH110594-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ilya E. Monosov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $403,619
- **Award type:** 2
- **Project period:** 2017-02-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10298264

## Citation

> US National Institutes of Health, RePORTER application 10298264, Neural Circuits that Regulate Risk Seeking (2R01MH110594-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10298264. Licensed CC0.

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