Epileptic responses in marmosets induced by knockdown of CREB Regulated Transcription Coactivator 1 (CRTC1)

Abstract

SummaryAnimal models have contributed greatly to the development of anticonvulsant drugs. However, 20-30% of epilepsy patients still do not achieve adequate seizure control. It is important to understand the biological mechanisms of epilepsy in order to develop treatments and novel anticonvulsant drugs. Here we reportCRTC1knockdown (KD) induced abnormalcFOSexpression beyond the injection sites followed by epileptic response by three local injections of short hairpin RNA (shRNA) in marmoset V1. Longitudinal monitoring of cortical-wide neural activity revealed transient changes in high frequency oscillations by cortical electrocorticography throughout the cortex, and a lesion in the temporal lobe was observed by MRI and postmortem histology.shCRTC1KD marmosets showed severe lesions surrounding the injection site several months after injection. Glial cell activation may occur simultaneously or prior to IEG induction aftershCRTC1injection. Thus, the epileptic process from seizure onset to remission can be studied in this animal model.