# Norepinephrine modulation of neocortex during flexible behavior

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $810,818

## Abstract

SUMMARY
Norepinephrine is a neurotransmitter thought to be involved in driving behavioral flexibility. It is released by a
small number of neurons throughout the neocortex. Little is known, however, about what signals these neurons
provide, and how targets in neocortex use those signals, in the context of well-controlled behaviors in
mammals. This proposal aims to determine functions of norepinephrine-releasing neurons in the locus
coeruleus, the primary source of forebrain norepinephrine. The behaviors to be studied involve different types
of flexibility: the ability to switch between using different sensory modalities to select the relevant one for
receiving a reward, and the ability to choose among different alternatives that yield reward with changing
probabilities. The goal of the project is to link action potentials from identified norepinephrine-releasing neurons
to membrane potential, action potentials, and calcium dynamics, in primary somatosensory cortex and
prefrontal cortex, in the context of flexible behavior.
Three aims test three hypotheses that address different mechanistic questions about the functions of
norepinephrine in neocortex: 1) norepinephrine acts in sensory cortex to modulate the perceptual outcome of a
sensory stimulus; 2) norepinephrine regulates switching between relevant sensory modalities; 3)
norepinephrine and prefrontal cortex activity correlate with dynamic updating of behavior. Simultaneous
measurements of activity of norepinephrine neurons and their targets in neocortex, during well-controlled
behavioral tasks in mice, will enable testing these three hypotheses. Ultimately, understanding when and
where norepinephrine is released in the brain will be necessary to understand flexible behavior in general, and
disorders of attention and mood that rely on norepinephrine signaling.

## Key facts

- **NIH application ID:** 10063585
- **Project number:** 5R01NS104834-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jeremiah Yaacov Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $810,818
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063585

## Citation

> US National Institutes of Health, RePORTER application 10063585, Norepinephrine modulation of neocortex during flexible behavior (5R01NS104834-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10063585. Licensed CC0.

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