# Diverstiy Supplement-Deep brain live imaging of cAMP and protein kinase A activities underlying synaptic- and circuit-level mechanisms during learned behaviors

> **NIH NIH R00** · NORTHWESTERN UNIVERSITY · 2024 · $60,800

## Abstract

Project Summary/Abstract
Many of the approved drugs used to treat a variety of diseases in children and adults target G-protein coupled
receptors (GPCRs). Furthermore, it is reported that two-thirds of those receptors couple to cyclic adenosine
monophosphate (cAMP) regulation. Despite the approved use of GPCR-mediated drugs, little is known about
the subsequent cAMP signaling in specific neural circuits and their contributions to synaptic transmission and
behavior. In the brain, cellular processes important for learning and memory involve the second messenger
cAMP, along with other downstream messengers, such as Protein Kinase A (PKA) to decode neuromodulatory
signals. The applicant, Anthony James (post-baccalaureate student) will combine the viral expression of a cell-
type specific cAMP or PKA sensor to monitor postsynaptic intracellular signaling and presynaptic optogenetics
to precisely manipulate neuronal signaling and/or pharmacology to induce changes in synaptic plasticity,
focusing on long-term depression (LTD) with two-photon microscopy. Using this approach, he will evaluate the
somatic and dendritic cAMP and/or PKA activity organization in response to light-activated induction of synaptic
plasticity. Also, Anthony will determine if expression of the cAMP or PKA sensor alters synaptic properties within
expressed cells using electrophysiology. We hypothesize that neuromodulatory signals generate distinct spatial
and temporal patterns of cAMP-mediated signaling, which mediates synaptic transmission resulting in
appropriate behaviors. Also, we further hypothesize that sensor expression will not alter the synaptic properties
of the neuron. The results obtained from this study will further elucidate the molecular mechanisms underlying
synaptic transmission involving GPCR-mediated cAMP signaling. Our proposal builds on the experiments
outlined in the parent award and will further strengthen the link of causality between synapse-specific activation
and subsequent cAMP-PKA signaling in mediating synaptic depression. These experiments are within the scope
of the parent award, which examines the spatiotemporal dynamics of cAMP-mediated signaling during synaptic
plasticity and learned behaviors. Anthony’s proposal employs optogenetic stimulation to activate a specific
subset of corticostriatal terminals to examine the resultant cAMP-mediated signaling. Anthony will receive
laboratory training in stereotaxic surgery, acute brain slice preparation, two-photon microscopy,
electrophysiology, and data analysis, as well as career development training in writing, scientific communication,
and networking. For Anthony’s training, I have recruited a co-mentor to provide complementary mentorship. With
our combined mentoring efforts, we will help Anthony in reaching his goal of attending graduate school to pursue
a PhD in neuroscience.

## Key facts

- **NIH application ID:** 10998988
- **Project number:** 3R00AA027740-04S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Shana M Augustin
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $60,800
- **Award type:** 3
- **Project period:** 2024-04-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998988

## Citation

> US National Institutes of Health, RePORTER application 10998988, Diverstiy Supplement-Deep brain live imaging of cAMP and protein kinase A activities underlying synaptic- and circuit-level mechanisms during learned behaviors (3R00AA027740-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10998988. Licensed CC0.

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