# The Spatial and Temporal Scale of Neuromodulation in Mouse Sensory Cortex

> **NIH NIH RF1** · BAYLOR COLLEGE OF MEDICINE · 2022 · $2,251,364

## Abstract

The neuromodulators acetylcholine (ACh) and norepinephrine (NE) are associated with an
activated cortical brain state characterized by an increase in the reliability of cortical responses
to external stimuli and enhanced performance on behavioral tasks. A key unresolved question is
the spatial and temporal scale at which these neuromodulators exert their effects. New methods
to directly record the local availability of ACh and NE simultaneously with the activity of neural
populations in mice opens up the possibility to answer this question. In a first set of experiments
we will test the hypothesis that neural signatures of the activated state may vary across cortex
due to spatial inhomogeneities in moment-to-moment neuromodulator availability. In a second
set of experiments we will test the hypothesis that mice can recruit neuromodulators
independently to auditory and visual cortex to enhance performance on a multimodal attention
task. Given that disruption of these systems is a key feature of a variety of human diseases
including Alzheimer’s disease, ADHD, and Autism Spectrum Disorders, understanding the
baseline variability in neuromodulator activity in healthy animals will be critical for identifying
subtle changes in the effects of neuromodulators that may occur in different disease states and
for evaluating the efficacy of treatments. From the perspective of neuroscientists attempting to
understand the encoding of stimuli in population activity, the effects of neuromodulators appear
as stimulus-independent noise that adds variability to sensory responses. Understanding the
spatiotemporal resolution of the effects of ACh and NE will enable modeling of these effects as
state variables shaping the response of cortical populations. The cortical effects of both ACh
and NE release in mice are strikingly similar to neural correlates of attention recorded in
humans and primates. While it is unlikely that mice have fine-grained spatial or feature attention
like humans, understanding the spatiotemporal dynamics of these two neuromodulators in mice
will be a significant step towards dissociating their influence on attentional mechanisms more
generally. Having a clear understanding of the relative time course of the influence of these two
neuromodulators on cortical processing will provide important constraints for future studies of
the cellular and circuit mechanisms underlying their effects.

## Key facts

- **NIH application ID:** 10524638
- **Project number:** 1RF1NS128901-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Jacob Reimer
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,251,364
- **Award type:** 1
- **Project period:** 2022-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524638

## Citation

> US National Institutes of Health, RePORTER application 10524638, The Spatial and Temporal Scale of Neuromodulation in Mouse Sensory Cortex (1RF1NS128901-01). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10524638. Licensed CC0.

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