# Adrenergic transmission properties and implication

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $391,638

## Abstract

PROJECT SUMMARY
 Norepinephrine (NE) and epinephrine (Epi) have been implicated in complex cognitive functions,
such as sensory processing, sleep-wake/arousal state transition and attention, in the brain, and other
biological processes in various tissues and organs, including the heart, pancreas and spleen.
Dysregulation of adrenergic transmission is linked to a number of neurological diseases, including
Alzheimer’s disease, depressive disorders and schizophrenia, as well as many other health problems,
including cardiovascular diseases, immune-deficiency and tumorigenesis.
 Despite the potential involvement of NE/Epi in myriad physiological and pathological conditions,
the precise regulation and exact functional role of adrenergic transmission remain poorly defined, due
primarily to limitations of available tools for monitoring NE/Epi. We have recently developed a family
of intensity-based G-protein-coupled receptor (GPCR) activation-based genetically encoded NE
(GRABNE) sensors by coupling a circular permutated green fluorescent protein (cpGFP) with a human
adrenergic receptor. While these GRABNE sensors allowed the first visualization of adrenergic
transmission, the sensors were suboptimal in determining synaptic properties of adrenergic
transmission. To facilitate NE/Epi research, we recently engineered high-performance GRABNE
sensors that allowed high-sensitivity and high-resolution visualization of adrenergic transmission events
at single release sites. The new sensors and preliminary data build up our confidence to test the
hypothesis that high-performance GRABNE sensors may resolve the adrenergic transmission
properties that could deduce the adrenergic functional role. This application follows two specific
aims: Aim 1 is to determine whether high-performance GRABNE sensors may resolve adrenergic
transmission properties, and Aim 2 is to test whether adrenergic transmission plays an essential role in
the precision- and attention-demanding behaviors. We expect the proposed experiments to
characterize the first set of fundamental synaptic properties of a new form of neuronal transmission and
define a novel, unique functional role for adrenergic transmission.

## Key facts

- **NIH application ID:** 10795881
- **Project number:** 5R01NS131670-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Mark Beenhakker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,638
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795881

## Citation

> US National Institutes of Health, RePORTER application 10795881, Adrenergic transmission properties and implication (5R01NS131670-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10795881. Licensed CC0.

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