Circuit mechanisms underlying chronic epilepsy in a mouse model of focal cortical malformation

Published: March 29, 2021, 1:03 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.21.054148v1?rss=1 Authors: Yang, W., Williams, A., Sun, Q.-Q. Abstract: How aberrant neural circuits contribute to chronic epilepsy remains unclear. Using a mouse model of focal cortical malformation with spontaneous seizures, we dissected the circuit mechanisms underlying epileptogenesis. Spontaneous and optogenetically induced hyperexcitable bursts in vivo were present in a cortical region distal to (> 1mm) freeze-lesion induced microgyrus, instead of a region near it. ChR2-assisted circuit mapping revealed ectopic interlaminar excitatory inputs from infragranular layers to layer 2/3 pyramidal neurons as a key component of the hyperexcitable circuitry. This disrupted balance between excitation and inhibition was prominent in the cortical region distal to the microgyrus. Consistently, the synapses of both parvalbumin-positive interneurons (PV) and somatostatin-positive interneurons (SOM) to pyramidal neurons were maladaptive in a layer- and site-specific fashion. Finally, closed-loop optogenetic stimulation of SOM, but not PV, terminated spontaneous spike-wave discharges. Together, these results demonstrate highly site- and cell-type specific synaptic reorganizations underlying chronic cortical epilepsy and provide insights into potential treatment strategies for this devastating neurological disorder. Copy rights belong to original authors. Visit the link for more info