Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory

Anh D Bui; Theresa M Nguyen; Charles Limouse; Hannah K Kim; Gergely G Szabo; Sylwia Felong; Mattia Maroso; Ivan Soltesz

doi:10.1126/science.aan4074

Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory

Science. 2018 Feb 16;359(6377):787-790. doi: 10.1126/science.aan4074.

Authors

Anh D Bui^{1

2}, Theresa M Nguyen³, Charles Limouse⁴, Hannah K Kim³, Gergely G Szabo³, Sylwia Felong³, Mattia Maroso³, Ivan Soltesz³

Affiliations

¹ Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA. adbui@stanford.edu.
² Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA.
³ Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.

Abstract

Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Electroencephalography
Epilepsy, Temporal Lobe / physiopathology*
Female
Male
Mice
Mice, Inbred C57BL
Mossy Fibers, Hippocampal / physiology*
Mossy Fibers, Hippocampal / physiopathology*
Neurons / physiology
Optogenetics
Seizures / physiopathology*
Spatial Memory / physiology*

Abstract

Publication types

MeSH terms

Grants and funding