# Mechanisms and function of firing rate homeostasis in cortical circuits

> **NIH NIH R35** · BRANDEIS UNIVERSITY · 2021 · $817,737

## Abstract

The overall goal of my NS-supported research program is to understand the mechanisms that
stabilize the function of central nervous system (CNS) microcircuits during experience-
dependent plasticity and learning. Over the past ~20 years of NS support we discovered and
characterized several forms of homeostatic plasticity, including synaptic scaling and intrinsic
homeostatic plasticity, that are postulated to sense perturbations in mean neuronal activity,
then bidirectionally adjust synaptic and cellular properties to keep activity within a set point
range. Our recent work has focused on a) identifying the cellular and molecular mechanisms of
these homeostatic forms of plasticity in order to bolster our mechanistic and functional
understanding, and to generate tools that allow us to selectively block homeostatic plasticity in
vivo; and b) to determine what aspect of neuronal activity is under homeostatic control in intact
CNS circuits in vivo. We recently showed that the mean firing rates of neocortical pyramidal
neurons in freely behaving animals return back to an individual baseline following prolonged
perturbations to sensory drive, strongly supporting the idea that neocortical neurons
homeostatically regulate their mean firing around an individual 'firing rate set point'. Such a
process is theoretically important for preventing circuit hypo- or hyperexcitability during
experience-dependent development, as well as to short-circuit the positive feedback nature of
Hebbian plasticity rules that can degrade memory fidelity. We now have (or are developing) the
tools to disrupt homeostatic plasticity and firing rate set points in vivo, allowing us to assess the
impact of this disruption on network function and memory storage. The major goals of my NS-
supported research program going forward are: 1) to determine how activity set points are built,
and how individual neurons can have set points that are orders of magnitude different from each
other; 2) to understand how multiple homeostatic mechanisms cooperate with each other to
stabilize network activity in the face of profound perturbations; and 3) to test the role of
synaptic scaling and intrinsic homeostatic plasticity in memory encoding and generalization.
These studies will have important implications for our understanding of neurological disorders
that arise from aberrant circuit excitability (epilepsy, autism-spectrum disorders). They may
also provide a new avenue into understanding disorders such as PTSD that are likely to arise
from excessive generalization during aversive learning.

## Key facts

- **NIH application ID:** 10145818
- **Project number:** 5R35NS111562-03
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** GINA G TURRIGIANO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $817,737
- **Award type:** 5
- **Project period:** 2019-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145818

## Citation

> US National Institutes of Health, RePORTER application 10145818, Mechanisms and function of firing rate homeostasis in cortical circuits (5R35NS111562-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145818. Licensed CC0.

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