Circuit Mechanisms Underlying Epileptogenesis in a Mouse Model of Focal Cortical Malformation.

ABSTRACT: The way in which aberrant neural circuits contribute to epilepsy remains unclear. To elucidate this question, we dissected the circuit mechanisms underlying epileptogenesis using a mouse model of focal cortical malformation with spontaneous epileptiform discharges. We found that spontaneous spike-wave discharges and optogenetically induced hyperexcitable bursts in vivo were present in a cortical region distal to (>0.7 mm) freeze-lesion-induced microgyrus, instead of near the microgyrus. ChR2-assisted circuit mapping revealed ectopic inter-laminar excitatory input from infragranular layers to layers 2/3 pyramidal neurons as the key component of hyperexcitable circuitry. This hyperactivity disrupted the balance between excitation and inhibition and was more prominent in the cortical region d

SUBMITTER: Yang W 

PROVIDER: S-EPMC7855923 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature