# Homeostatic Metaplasticity in Rat Hippocampal Neural Circuits

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $38,190

## Abstract

ABSTRACT
The hippocampus contains dense patterns of synaptic connectivity that allows for sophisticated information
processing but makes this network vulnerable to instability. In recent years, homeostatic forms of synaptic
plasticity (HSP) have been recognized to play a central role in buffering destabilizing levels of activity in neural
circuits. Perhaps the most widely studied form of HSP is “synaptic scaling,” a process whereby synapses are
enhanced or depressed multiplicatively in response to chronic changes in neural firing rate. Although synaptic
scaling has been extensively studied and linked to a number of neurological and neuropsychiatric disorders,
the slow time-course over which scaling occurs has remained a perplexing feature of this adaptive form of
plasticity. Reasoning that the temporal dynamics of scaling might be dependent on the activity-dependent
history of the circuit, my preliminary experiments have examined how prior experience with scaling shapes the
magnitude and time-course of adaptation to future activity challenges. Surprisingly, I have found hippocampal
neuron networks respond to destabilizing levels of activity differently depending on their activity-dependent
history, suggesting a novel form of metaplasticity that potently regulates the induction of synaptic scaling. The
long-term goal of this research is to understand the contribution of activity-dependent epigenetic changes to
the metaplastic regulation of HSP in hippocampal neurons. The central hypothesis guiding this proposal is that
synaptic scaling induces lasting epigenetic changes which subsequently alters the intrinsic and/or synaptic
properties of neurons, fundamentally altering the ability to shift synaptic weights in response to additional
activity manipulations. This work will use cutting edge electrophysiological, imaging, and sequencing methods
to determine the functional significance of transcription-level changes to the metaplastic regulation of synaptic
scaling and how this impacts the stability of the overall network. By characterizing this novel aspect of synaptic
scaling, this project will provide insights into fundamental aspects of homeostatic regulation in neural circuits.

## Key facts

- **NIH application ID:** 9979956
- **Project number:** 5F31MH117887-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Alex Chen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,190
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979956

## Citation

> US National Institutes of Health, RePORTER application 9979956, Homeostatic Metaplasticity in Rat Hippocampal Neural Circuits (5F31MH117887-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9979956. Licensed CC0.

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