# Mechanisms of basal forebrain control over sensory processing

> **NIH NIH R00** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $224,101

## Abstract

PROJECT SUMMARY
A key problem in neuroscience is understanding how internal and external information are integrated in the brain to produce
sensory experiences, cognition, and behavioral responses. This integration relies on flexible modulation of sensory
processing in response to behavioral states like motivation, attention, and arousal. Neurons in the basal forebrain are key
mediators of these behavioral states. At the same time, basal forebrain neurodegeneration in Alzheimer’s and Parkinson’s
disease is associated with deficits in both cognitive and sensory processing. Olfactory deficits are especially common across
neurodegenerative and neuropsychiatric diseases, particularly those associated with dementia. While it has been
hypothesized that olfaction and cognitive processing are linked by common upstream regulatory systems, the circuit
mechanisms mediating this control remain unknown. Therefore, the goal of this proposal is to develop a mechanistic
understanding of how neural circuits in the basal forebrain impact sensory processing. The proposed Aims test the
hypothesis that effects of attention, arousal, and reward prediction on olfactory processing rely on precisely timed,
cholinergic signaling within the basal forebrain controlling projection output to the olfactory bulb. In the mentored K99
phase (Aim 1), I will investigate the impact of behavioral state on odor coding in the olfactory bulb using meso-scale, in
vivo two-photon imaging. Under the mentorship of Drs. Ben Arenkiel and Paul Pfaffinger, and with the collaboration of
Drs. Jacob Reimer and Ankit Patel, I will be trained in the technical aspects of meso-scale two-photon microscopy and
computational methods. As I transition to independence in the R00 phase, I will look upstream to processing in the basal
forebrain where I will use a combination of electrophysiology, optogenetics, fiber photometry, and targeted genetic
manipulations to determine how cell type specific, state-dependent signaling within the basal forebrain influences olfactory
learning (Aim 2). Finally, in Aim 3 I will test the hypothesis that basal forebrain cholinergic and GABAergic neurons play
distinct roles in olfactory learning, via impacts on odor processing in the olfactory bulb. To test this, I will use a combination
of targeted genetic manipulations, olfactory-based behavioral platforms, meso-scale two-photon imaging, and fiber
photometry. Together the proposed research will reveal cellular and circuit mechanisms underlying basal forebrain control
of olfactory sensory processing in the healthy brain. Ultimately, this addresses the question of how basal forebrain
dysfunction impacts sensation and cognition in disease, and it will provide the conceptual framework for a future
independent research program.

## Key facts

- **NIH application ID:** 10906133
- **Project number:** 5R00DC019505-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Elizabeth Hanson Moss
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $224,101
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906133

## Citation

> US National Institutes of Health, RePORTER application 10906133, Mechanisms of basal forebrain control over sensory processing (5R00DC019505-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906133. Licensed CC0.

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