# Homeostatic Stabilization of Neural Function in Health and Disease

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $1,174,199

## Abstract

PROJECT SUMMARY/ABSTRACT
The brain is astonishing in its complexity and capacity for change. It seems certain that the plasticity that drives
our ability to learn and remember can only be meaningful in the context of otherwise stable, reproducible, and
predictable baseline neural function. It is now clear that homeostatic signaling systems function throughout the
central and peripheral nervous systems to stabilize neural function throughout life. As a consequence, it is
widely believed that impaired or maladaptive homeostatic signaling will be directly relevant to the cause and
progression of neurological diseases that include epilepsy, autism and neurodegeneration. However, despite
widespread evidence for the homeostatic control of neural function throughout the animal kingdom and implicit
relevance to disease and aging, very little is known about the underlying mechanisms. The field of homeostatic
plasticity is wide open for exploration and the potential for transformative advancement in cellular and
molecular neuroscience is tremendous. We are leading the rapidly emerging field of homeostatic plasticity,
harnessing the power of unbiased model system genetics to identify and characterize fundamentally new
cellular and molecular mechanisms of homeostatic signaling in the nervous system. Our experiments will
define many of the first signaling pathways identified to participate in the homeostatic signaling systems that
control presynaptic neurotransmitter release and intrinsic neural excitability. Our approaches have uncovered a
novel activity of the innate immune signaling system, new trans-synaptic signaling pathways, novel calcium
sensors, novel neuronal kinase signaling systems, new roles for the presynaptic endoplasmic reticulum and
tangible links to neurological disease. As such, our data will provide a foundation for exploring the impact
homeostatic plasticity in mammalian models of neurological disease including epilepsy, autism and
neurodegeneration. Our data will also directly impact current theories and models of homeostatic signaling.
Current theoretical models have captured widespread interest. Molecular insight will provide important new
ideas and new constraints for the next generation of theoretical models of homeostatic plasticity, learning and
memory.

## Key facts

- **NIH application ID:** 10312780
- **Project number:** 5R35NS097212-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** GRAEME W DAVIS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,174,199
- **Award type:** 5
- **Project period:** 2016-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312780

## Citation

> US National Institutes of Health, RePORTER application 10312780, Homeostatic Stabilization of Neural Function in Health and Disease (5R35NS097212-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10312780. Licensed CC0.

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