# The role of intrinsic cellular excitability in homeostatic plasticity of developing circuits

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $362,900

## Abstract

Abstract
It is an extraordinary accomplishment that most developing neuronal networks
achieve an appropriate level of excitability, during a dynamic period of embryonic
development when there are several challenges to a network's excitability. Errors
in such a complicated process can lead to alterations in the excitability of neonatal
spinal circuit, which can be observed behaviorally as myoclonus, hypertonia, recurrent
tremor, and spasticity. Understanding the rules and mechanisms that underlie the
maturation of network excitability are therefore essential. An exciting new field has
emerged, which provides critical insights to understanding the rules that networks
follow in order to achieve appropriate levels of activity. Many studies have now
shown that perturbations to network activity trigger changes in synaptic strength
which are thought to homeostatically recover and maintain activity levels within an
appropriate range. Compensatory changes in intrinsic cellular excitability (cell's
responsiveness to synaptic input) also likely contribute to the homeostatic process,
although these changes have received far less attention than synaptic
compensations. By taking advantage of the accessibility of the chick embryo we
have been able to follow an actual homeostatic recovery of activity (embryonic
movements). Because of this, we have been able to identify a critical and
previously unrecognized homeostatic mechanism where changes in resting
membrane potential mediate the initial homeostatic recovery of perturbed activity
levels in the living embryonic spinal cord. We will identify the mechanism
underlying this compensation in the first aim of the grant. Based on a recent study
and our proteomic analysis from our previous grant period, we are proposing to
examine an unexpected critical relationship between mitochondrial function and
homeostatic plasticity in aim 2. Finally in aim 3 we will carry out this work in the
genetically advantageous mouse model system. Our study will identify the
mechanisms of homeostatic plasticity in the living system and will begin to elucidate the
calcium triggers for these forms of plasticity. The work can instruct pharmacological
interventions that ameliorate hyperexcitability associated with neurodevelopmental
disorders, and help us better understand the function of homeostatic plasticity.

## Key facts

- **NIH application ID:** 9974093
- **Project number:** 2R01NS065992-09
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** PETER A WENNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,900
- **Award type:** 2
- **Project period:** 2010-09-17 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974093

## Citation

> US National Institutes of Health, RePORTER application 9974093, The role of intrinsic cellular excitability in homeostatic plasticity of developing circuits (2R01NS065992-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974093. Licensed CC0.

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