# Adrenergic signaling in the CNS in health and disease

> **NIH NIH F99** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $38,924

## Abstract

Abstract
In the central nervous system (CNS), beta adrenergic receptors (BARs) are broadly expressed responding to
norepinephrine (NE) signaling from projections from the Locus Coeruleus. NE regulates attention, arousal,
and acuity as well as fear learning in health and is implicated in neurodegenerative disorders. Beta2 adrenergic
receptors (B2ARs) are involved in long term potentiation through Gs-mediated activation of protein kinase A
(PKA) regulating calcium channels and AMPA receptors. In addition to G-protein signaling activities, the B2AR
itself can be modified affecting downstream signaling, including precise spatiotemporal regulation of signals in
highly differentiated neurons. Little is known about the impacts these phosphorylation events have on NE-
mediated receptor signaling and behavioral phenotypes. This dissertation research addresses this knowledge
gap, examining signaling mechanisms of B2AR phosphorylation, the signaling and behavioral consequences of
those phosphorylation events, and examines the role these phosphorylation events play in Parkinson’s disease
(PD). Recently our lab found functionally distinct and selectively phosphorylated subpopulations of B2ARs
exist in single neurons. These B2AR subpopulations are selectively phosphorylated at either a PKA (S261/262)
or G-protein receptor kinase (GRK) (S355/356) site on the c-terminus of the receptor. Preliminary data show
that GRK phosphorylation is necessary to promote signaling to the nucleus and gene expression, and also
demonstrated that GRK-mediated B2AR signaling is protective against toxin mediated nigral neuron death in a
model of PD. These data indicate that distinct subpopulations of B2AR are involved in multiple forms of
learning and memory and disease processes. In this proposal, we hypothesize that GRK-mediated
phosphorylation of B2AR controls the signaling mechanism by which B2AR promotes gene expression involved
in memory and learning in health and is neuroprotective against toxin induced neuronal death in a PD model.
Data and skills developed in this proposal will form the foundation of postdoctoral research examining B2AR
signaling in Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10146188
- **Project number:** 1F99NS120523-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Joseph M Martinez
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,924
- **Award type:** 1
- **Project period:** 2020-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146188

## Citation

> US National Institutes of Health, RePORTER application 10146188, Adrenergic signaling in the CNS in health and disease (1F99NS120523-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146188. Licensed CC0.

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