# Christen Crosta_Diversity Supplement: 1 R21 NS122159

> **NIH NIH R21** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $92,699

## Abstract

PROJECT SUMMARY
Dendrite morphology determines many aspects of neuronal function, including action potential propagation and
information processing. Although emerging evidence suggests that dendrite growth and branching is regulated
locally, the lack of optimal measurements at local sites exists. Brain-derived neurotrophic factor (BDNF) is one
of the most studied regulators of dendrite development, and we reported that BDNF exerts distinct local effects
on the dendritic arbor depending on where on the arbor it is applied. BDNF triggers PKA activation to regulate
dendrite branching, yet not much is known about how BDNF activates PKA to promote local dendrite
branching. The proposed work aims to utilize cAMP-dependent protein kinase (PKA) activation sensors as part
of a Fӧrster resonance energy transfer (FRET)-based imaging platform to study the spatiotemporal regulation
of the dendritic arbor by PKA activation. First, we will locally apply PKA activator or inhibitor to the dendrite and
show a functional relationship between PKA activity and dendrite branching. A microtubule targeted A-kinase
activity reporter (tAKAR4α) that shows high sensitivity and dynamic range and is activated by neuromodulators
will be expressed in cultured embryonic rat hippocampal neurons of both sexes. We will measure the time-
dependent dynamic distribution of PKA in neurons as dendrites develop and branch over time. Second, it has
been reported that nuclear signaling of activated PKA occurs and is highest after stimulation of secondary
versus other order dendrites, regardless of distance from the soma. As such, we will construct a new PKA
activation sensor, tAKAR4n, that will be targeted to the nucleus and use this new FRET sensor to determine
whether nuclear PKA activity increases when secondary, but not other order, dendrites are stimulated with
PKA activator. Third, we will use the tAKAR4a FRET sensor and nuclear-targeted AKAR4 probe to determine
the mechanism by which BDNF locally regulates the arbor. These studies will shed light on mechanisms that
shape neuronal morphology that can then be targeted for therapeutics to restore neuronal connectivity and
circuitry after injury due to stroke or TBI or as a result of neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10519715
- **Project number:** 3R21NS122159-01S1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Nada Boustany
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $92,699
- **Award type:** 3
- **Project period:** 2022-01-18 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519715

## Citation

> US National Institutes of Health, RePORTER application 10519715, Christen Crosta_Diversity Supplement: 1 R21 NS122159 (3R21NS122159-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10519715. Licensed CC0.

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