# Optogenetic control of seizures via the basal ganglia

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2020 · $386,920

## Abstract

Abstract
While a heightened risk of seizures in Alzheimer’s Disease (AD) has been observed in sporadic studies from the
1980s to the present, the extent of comorbidity, and the implications for seizures to influence AD progression
and outcomes is only now coming to be appreciated. While in the general population, the risk of epilepsy is ~1%,
some studies have found the risk in AD to be up to 8-10%. The goal of the parent grant is to understand the
circuit mechanisms by which neuromodulation in the basal ganglia can control seizures, with the ultimate goal
of identifying new deep brain stimulation targets for epilepsy, such as the deep and intermediate layers of the
superior colliculus (DLSC). While a small, but growing, number of studies have evaluated pharmacotherapy as
an intervention for seizures in AD models, none, to the best of our knowledge have employed brain stimulation
approaches, representing a gap in knowledge. The proposed supplement aims to address this gap in knowledge
through two aims. In Aim 1, we will test the hypothesis that open and closed-loop optogenetic activation of the
superior colliculus will suppress spontaneous non-convulsive seizures in the TgF344-AD rat model of AD. This
represents one of the two major seizure types seen in patients with AD. In Aim 2, we will address the other major
seizure type, temporal lobe (limbic) seizures. We will test the hypotheses that TgF344-AD rats will display
enhanced limbic epileptogenesis after status epilepticus, that FgF344-AD rats will display more severe
impairments in cognition after status epilepticus, and that spontaneous seizures after status epilepticus will be
reduced by optogenetic stimulation of the DLSC. Through these aims, we will determine if a promising preclinical
brain stimulation approach will also be useful against seizures in a model of AD, determine how AD pathology
and cognitive dysfunction are impacted by an epileptogenic insult, and model both of the major seizure types
observed in patients with AD.

## Key facts

- **NIH application ID:** 10123790
- **Project number:** 3R01NS097762-05S1
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Patrick Alexander Forcelli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,920
- **Award type:** 3
- **Project period:** 2016-07-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123790

## Citation

> US National Institutes of Health, RePORTER application 10123790, Optogenetic control of seizures via the basal ganglia (3R01NS097762-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10123790. Licensed CC0.

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