# Cellular and molecular mechanisms of dendritic spine growth and stabilization in health and disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $706,959

## Abstract

Abstract
One of the most remarkable properties of the brain is its ability to undergo adaptive modifications in
response to changing environments. This experience-dependent plasticity is essential not only for the fine-
tuning of developing circuits, but also for learning in adults. Advanced fluorescent labeling and imaging
techniques have enabled direct visualization of the structural and functional reorganization of neuronal
circuits during learning. Dendritic spines have been a major focus of these studies; spine gain or loss is
associated with formation or elimination of neural circuit connections, and the enlargement or shrinkage of
spines accompanies increases or decreases in the strength of synaptic connections. Notably, neurological
and neurodegenerative disorders that result in cognitive dysfunction and disrupt learning are usually
associated with changes in the density or morphology of dendritic spines. The long-term goal of this
research proposal is to elucidate the molecular signaling mechanisms that regulate the growth, stabilization,
and functional maturation of dendritic spines and their associated synapses during the activity-dependent
synaptic plasticity that is associated with learning. To achieve this goal, we will use two-photon imaging and
photostimulation techniques combined with genetically-encoded biosensors and fluorescence lifetime
imaging to measure spatiotemporal signaling in neuronal dendrites, and molecular genetic,
pharmacological, biochemical and proteomic techniques to identify key signaling pathways and complexes
that regulate excitatory synapse plasticity. In Aim 1, we will delineate the unexpected role of the RhoGEF
Ephexin5 and its downstream signaling pathways the activity-dependent spine growth and stabilization that
is vital for learning and how these pathways are altered in cellular models for studying Alzheimer’s disease.
In Aim 2, we will elucidate the novel non-enzymatic roles and interactions partners of CaMKII in nascent
spine growth and stabilization as new circuit connections are established and we will define how these
signaling pathways contribute to synaptic dysfunction in models for studying Alzheimer’s disease. Results
from these experiments will rigorously address novel and unexpected molecular mechanisms of excitatory
synapse growth and stabilization, thereby filling gaps in our current understanding of learning-associated
neural circuit plasticity, with the ultimate goal to facilitate the development of therapeutics for human
diseases associated with intellectual disability.

## Key facts

- **NIH application ID:** 11072888
- **Project number:** 1R01NS137635-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Karen Zito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $706,959
- **Award type:** 1
- **Project period:** 2024-09-18 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11072888

## Citation

> US National Institutes of Health, RePORTER application 11072888, Cellular and molecular mechanisms of dendritic spine growth and stabilization in health and disease (1R01NS137635-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11072888. Licensed CC0.

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