# Basal Forebrain Non-cholinergic Circuit Mechanisms of Sustained Attention

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $582,487

## Abstract

ABSTRACT
The long-term goal is to understand how basal forebrain (BF) circuits underlie cognitive functions like
sustained attention. Traditionally, BF was thought to mediate attention through its cholinergic neurons
and cortical acetylcholine release. However, recent recordings suggest that cholinergic signaling
reflects arousal and reinforcement learning instead. If not cholinergic neurons, what alternative BF
circuits support attention?
The objective of this proposal is to determine the circuit and behavioral roles of an understudied BF
population: parvalbumin-expressing GABAergic neurons (BF-PV) that project to the cortex. Our
previous work using a sustained attention-demanding auditory detection task revealed that BF
cholinergic neurons respond to reinforcement surprises, independent of temporal fluctuations of
attention. This discovery prompted an investigation into alternative BF neuron types. Our preliminary
studies suggest that BF-PV neurons have key attributes relevant for sustained attention: their activity
predicts detection accuracy and reaction time on a trial-by-trial basis, and their optogenetic stimulation
enhances performance.
Using quantitative behavior, cell-type-specific recordings and manipulations, viral tracing, and
computational modeling, we aim to explore the link between BF-PV neurons and sustained attention.
Aim 1 will map BF-PV cortical projections and investigate whether they produce cortical gain control
through disinhibition. Aim 2 will record BF-PV neuron activity to assess how its dynamics predict
momentary attention levels during sustained attention tasks and use optogenetics to evaluate their
necessity and sufficiency. Aim 3 seeks to determine if BF-PV neurons convey motivational salience
signals that guide attention allocation.
This work will elucidate how long-range, cortex-projecting BF-PV neurons support sustained attention,
distinguishing their contributions from known cholinergic effects. Defining the computations and
connectivity underlying sustained attention will provide fundamental insights into basal forebrain circuits
for normal cognition. Illuminating this poorly understood pathway may also reveal new therapeutic
targets for attention disorders and BF-related dementias like Alzheimer's and Parkinson's disease.

## Key facts

- **NIH application ID:** 10946455
- **Project number:** 1R01MH137463-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Adam Kepecs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $582,487
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10946455

## Citation

> US National Institutes of Health, RePORTER application 10946455, Basal Forebrain Non-cholinergic Circuit Mechanisms of Sustained Attention (1R01MH137463-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10946455. Licensed CC0.

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