# Co-engineering Hebbian and Homeostatic Plasticity Mechanisms to Induce Targeted Functional Neural Connectivity Changes

> **NIH NIH F99** · UNIVERSITY OF WASHINGTON · 2024 · $49,974

## Abstract

Project Summary:
Our memories and behaviors are encoded by the plastic changes in connectivity between the trillions of synapses
connecting the neurons in our brains. Neurological disorders such as schizophrenia, epilepsy, and stroke often
result in aberrant neural connectivity that causes debilitating deficits in cognition and behavior. One approach to
treating these disorders is to harness the brain’s natural plasticity mechanisms to restore lost function following
injury through neural stimulation. These plastic connectivity changes occur through two main identified
mechanisms: Hebbian and homeostatic plasticity. In accordance with Hebbian plasticity mechanisms,
connections are strengthened or weakened when activity between neurons is correlated or uncorrelated,
respectively. Stimulation-based approaches attempt to utilize this mechanism for inducing plastic changes with
limited efficacy to strengthen connectivity (long-term potentiation, LTP), while neglecting the effects of
homeostatic plasticity mechanisms. Homeostatic plasticity mechanisms alter connectivity to maintain consistent
neuronal activity levels by modifying synaptic strengths, levels of inhibition, and the threshold for LTP induction
based on previous activity levels. Here, I hypothesize that homeostatic plasticity plays a significant role in
determining Hebbian-informed stimulation-induced plasticity outcomes and that both mechanisms of plasticity
can be engineered to improve these outcomes towards strengthening corticocortical connectivity. In aim 1, I
assess the impact of reducing neuronal activity on Hebbian-informed stimulation-induced functional connectivity
changes in healthy and diseased states. In the diseased state, I will measure the impact of this strategy on
promoting functional recovery following targeted cortical lesioning. In aim 2, I explore the suppression of
homeostatic plasticity mechanisms that oppose Hebbian-informed stimulation-induced functional connectivity
changes. The outlined research strategy will allow me to build experimental and professional skills that will propel
my career as I transition into a postdoctoral position. By incorporating homeostatic plasticity mechanisms in the
design of Hebbian-based stimulation protocols for targeted neural connectivity change, the findings of the
proposed study can transform the efficacy of future stimulation-based therapies for neurological disorders.

## Key facts

- **NIH application ID:** 10879082
- **Project number:** 5F99NS130828-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Karam Khateeb
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,974
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879082

## Citation

> US National Institutes of Health, RePORTER application 10879082, Co-engineering Hebbian and Homeostatic Plasticity Mechanisms to Induce Targeted Functional Neural Connectivity Changes (5F99NS130828-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10879082. Licensed CC0.

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