# NEURAL CIRCUITS MEDIATING UNCERTAINTY AND THEIR EFFECT ON BEHAVIOR

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,250

## Abstract

Project Summary
We live in an uncertain world in which events and outcomes are often unpredictable. Being able to flexibly
modify our behavior based on our uncertainty about important future outcomes, such as rewards, is critical for
survival. Many studies have reported that reward uncertainty modulates behavioral and emotional states, and
that improper evaluation of uncertainty is associated with maladaptive behaviors, such as risk-seeking, anxiety,
and addiction. Recent evidence suggests that within the brain there are populations of neurons devoted to
signaling uncertainty. But how this signal is broadcast and utilized is unknown. We will test the hypothesis that
the basal forebrain (BF) plays a major role in broadcasting this signal. We will further test the idea that medial
and dorsal-lateral subregions of BF differentially contribute to the regulation of behavior in uncertain contexts.
In Aim 1, we will test whether and how different subregions of the primate BF signal and combine information
about uncertainty and value. The medial BF is thought to be crucial for learning and monitoring of important
events, and dorsal-lateral portions of the BF, known as the ventral pallidum or the ventral-rostral globus
pallidus, are thought to regulate motivation. If this is true, then it seems likely that these two BF subregions
might represent uncertainty in very different ways. Next, we propose to examine how the differential
representations of uncertainty and value in different regions of the BF contribute to behavior. If dorsal-lateral
BF regulates motivation, then it is possible that uncertainty-signals there modulate uncertainty-related
behaviors, such as risk-seeking. To test this hypothesis, we will study BF activity while monkeys choose
between certain and uncertain rewards. Preliminary data support the hypothesis that dorsal-lateral BF's
uncertainty representation is correlated with risky-choices, while medial BF's uncertainty signals emerge after
the risky choice, while the subject awaits the choice-outcome. Finally, we will transiently inactivate different
subregions of BF to causally test how the differential neuronal encoding of uncertainty in those regions
contributes to choice behavior. In Aim 2 we will test whether a major input to the dorsal-lateral BF, the
striatum, is a source of the uncertainty signal we observed there. Based on data gathered during preliminary
experiments, we hypothesize that uncertainty coding neurons clustered in the internal capsule bordering region
of the striatum could be the source of uncertainty modulation observed in dorsal-lateral BF. To causally test
this hypothesis, the last experiment in Aim 2 will assess whether inactivation of this striatal area reduces the
uncertainty sensitivity of neurons in the BF.
Uncertainty about rewards modulates motivation and decision making. Our proposed experiments will provide
crucial information about the neuronal mechanisms of behavioral modulation by uncertainty. Unders...

## Key facts

- **NIH application ID:** 9825432
- **Project number:** 5R01MH110594-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ilya E. Monosov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2017-02-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825432

## Citation

> US National Institutes of Health, RePORTER application 9825432, NEURAL CIRCUITS MEDIATING UNCERTAINTY AND THEIR EFFECT ON BEHAVIOR (5R01MH110594-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9825432. Licensed CC0.

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