# Sleep-Wake and Epilepsy Interactions in a Mouse Model of Temporal Lobe Epileps

> **NIH NIH R21** · EMORY UNIVERSITY · 2021 · $429,995

## Abstract

PI: Pedersen R21 – June, 2020
PROJECT SUMMARY/ABSTRACT
Epilepsy affects more than three million people in the US alone, with most reporting a relationship between
seizures and sleep-wake patterns, and about one million having sleep disorders. Furthermore, many of the
comorbidities of epilepsy, such as mood disorder, attentional and executive difficulties, memory dysfunction, and
psychosis, are worsened by disrupted sleep. Despite this long-appreciated and robust relationship between
sleep-wake and epilepsy, little is known about the underlying mechanisms of this interaction. The long-term
objective of this work is to understand better key large-scale brain circuits, namely those that control sleep-wake
and how they influence seizure frequency and severity. The overall hypothesis is that careful manipulations of
component cell groups of sleep-wake circuits can be used to treat epilepsy and seizures, potentially including
some comorbidities of epilepsy. We hypothesize, also based on preliminary findings, that the intra-amygdala
kainic acid model of medial temporal lobe epilepsy in mice will show sleep disruptions that are similar to those
of people with epilepsy. We further hypothesize that circuit-based manipulations of sleep-wake control circuits
will have predictable effects on seizures, with increases in sleep reducing seizures and decreased sleep further
worsening epilepsy. We examine these hypotheses in two Specific Aims using a novel purpose-build head plate
that permits rapid implantation of microinjection cannula, screw, neck muscle, and depth electrodes in mice. The
first Aim examines the mutual influence of sleep-wake and seizures in the mouse intra-amygdala kainic acid
model of temporal lobe epilepsy. Preliminary data shows dramatic sleep disruption of sleep in mice with seizures
and that seizures are associated with slow-wave sleep and rare in rapid eye movement sleep. The second Aim
includes two experiments: One examines the effect of chemogenetically increasing sleep, by activating inhibitory
neurons of the parafacial zone of the brainstem; the other activates a vital component of the hypothalamic arousal
network, the supramammillary nucleus, that drives wake without sleep rebound. We anticipate that seizures will
be reduced by increased sleep and worsened by prolonged wakefulness, respectively. This work Aims to provide
a new line of research targeting other sleep-wake nuclei, a new avenue for epilepsy research that focuses on
large-scale modulatory circuits and brings together sleep-wake and epilepsy research. We hope that this work
will improve our understanding of brain function and help develop novel approaches to the treatment of epilepsy.
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## Key facts

- **NIH application ID:** 10196519
- **Project number:** 1R21NS122011-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Nigel Paul Pedersen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,995
- **Award type:** 1
- **Project period:** 2021-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196519

## Citation

> US National Institutes of Health, RePORTER application 10196519, Sleep-Wake and Epilepsy Interactions in a Mouse Model of Temporal Lobe Epileps (1R21NS122011-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10196519. Licensed CC0.

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