# Optogenetic control of seizures via the basal ganglia

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2020 · $340,156

## Abstract

Epilepsy is the second most prevalent neurological disorder, affecting approximately 2 million people in the
United States. While many patients achieve satisfactory seizure control with pharmacotherapy, there is a
significant proportion (20-40%) who have medically intractable seizures. For these patients identification of novel
methods for seizure control is a high priority. One such method may be to harness endogenous seizure
suppressive circuits in the brain. Because seizures may have multiple or unknown sites of initiation, focal
stimulation approaches (e.g., deep brain stimulation [DBS]) that can control seizures originating in diverse brain
networks are highly desirable. The circuitry of the basal ganglia has received particular attention in this regard.
 Here, we propose to employ optogenetic methodologies to analyze the contribution of the nigrotectal pathway
and its descending projections to the pedunculopontine nucleus to seizure control. The SNpr is major source of
inhibitory input to DLSC. Moreover, both DLSC and SNpr both provide synaptic input to PPN. In Aim 1, we will test
the hypothesis that optogenetic silencing of the SNpr, activation of DLSC, or silencing of SNpr to DLSC projections
will control spontaneous recurrent seizures in a post-status epilepticus model. In Aim 2, we will determine if
projections from SNpr/DLSC to the PPN are necessary and sufficient to account for basal-ganglia mediated seizure
control. We will dissect the contribution of multiple cell types within the PPN, separately analyzing glutamatergic and
cholinergic cell groups.
 In the service of these aims, we will examine the effects of optogenetic manipulations on complementary
spontaneous and evoked seizure models to map the contributions of this network to seizure suppression within
divergent seizure circuits. Together the proposed studies will provide proof of principle for optogenetic modulation of
seizures in diverse networks from a single circuit. Moreover, this approach allows us to examine previously
untestable hypotheses about the connections that mediate basal ganglia seizure control. Finally, the proposed
experiments aim to uncover the circuit and neurotransmitter mechanism by which focal manipulations in motor
control regions (i.e., SNpr/DLSC) translate into brain-wide changes in excitability.

## Key facts

- **NIH application ID:** 9954161
- **Project number:** 5R01NS097762-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Patrick Alexander Forcelli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,156
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954161

## Citation

> US National Institutes of Health, RePORTER application 9954161, Optogenetic control of seizures via the basal ganglia (5R01NS097762-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9954161. Licensed CC0.

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