# Neuromodulatory regulation of cortical functional connectivity

> **NIH NIH R21** · YALE UNIVERSITY · 2024 · $250,913

## Abstract

PROJECT SUMMARY:
Neuromodulatory signaling is thought to play key roles in regulating the activity of local and long-range circuits
in the brain and in mediating behavioral state-dependent changes in circuit function and cognition. Despite
extensive anatomical evidence, there is little functional data on neuromodulatory signaling across the cortex
during behavior. Recent work has highlighted the complex, state-dependent spatiotemporal pattern of
acetylcholine (ACh) release in the neocortex. In contrast, little is known about the spatiotemporal dynamics of
norepinephrine (NE) signaling. Previous work has suggested that fluctuations in cholinergic and noradrenergic
signals may occur in tight coordination, particularly at moments of transition between behavioral states such as
quiescence and arousal. However, technical limitations have precluded simultaneous observation of multiple
neuromodulatory systems. To address these gaps, we propose to combine novel imaging approaches, including
multicolor wide-field `mesoscopic' imaging of neuronal, NE, and ACh signaling across the entire cortex in awake
behaving animals, with high-density electrophysiology and pharmacological manipulations. Using this
combination of imaging and electrophysiology, we will test the following hypotheses: (1) Noradrenergic signaling
regulates cortical activity at key transitions between behavioral states. (2) Noradrenergic and cholinergic
signaling patterns exhibit selective spatiotemporal coordination. Our results will provide an unprecedented level
of insight into the relationship between noradrenergic signaling and neocortical activity and provide novel data
on coordination between neuromodulatory systems.

## Key facts

- **NIH application ID:** 10904202
- **Project number:** 1R21EY036254-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JESSICA A CARDIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,913
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904202

## Citation

> US National Institutes of Health, RePORTER application 10904202, Neuromodulatory regulation of cortical functional connectivity (1R21EY036254-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904202. Licensed CC0.

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