Position- and Time-Dependent Arc Expression Links Neuronal Activity to Synaptic Plasticity During Epileptogenesis

Frontiers in Cellular Neuroscience
Philipp JanzCarola A Haas

Abstract

In mesial temporal lobe epilepsy (mTLE) an initial precipitating injury can trigger aberrant wiring of neuronal circuits causing seizure activity. While circuit reorganization is known to be largely activity-dependent, the interactions between neuronal activity and synaptic plasticity during the development of mTLE remain poorly understood. Therefore, the present study aimed at delineating the spatiotemporal relationship between epileptic activity, activity-dependent gene expression and synaptic plasticity during kainic acid-induced epileptogenesis in mice. We show that during epileptogenesis the sclerotic hippocampus differed from non-sclerotic regions by displaying a consistently lower power of paroxysmal discharges. However, the power of these discharges steadily increased during epileptogenesis. This increase was paralleled by the upregulation of the activity-related cytoskeleton protein (Arc) gene expression in dentate granule cells (DGCs) of the sclerotic hippocampus. Importantly, we found that Arc mRNA-upregulating DGCs exhibited increased spine densities and spine sizes, but at the same time decreased AMPA-type glutamate receptor (AMPAR) densities. Finally, we show that in vivo optogenetic stimulation of DGC synapses ev...Continue Reading

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Citations

Apr 8, 2020·Frontiers in Neuroscience·Afrinash AhamadGregory W Kirschen
Sep 8, 2019·Neuropharmacology·Allison KirchnerJeffrey A Loeb
Jul 13, 2021·Frontiers in Pharmacology·Jing-Jun ZhengMei Zhang

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Methods Mentioned

BETA
electron microscopy
in vitro transcription
restriction digest
Fluorescence
transmission electron microscopy

Software Mentioned

Prism
Imaris
ZEN blue
Fiji ImageJ
Fiji Image J
Spike2
ImageSP
GraphPad

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