Calcium activity during interictal spikes in chronic kainate - induced epilepsy
Miklós Madarász1, Tibor Lőrincz1, Gábor Juhász1, Tímea Szabó2, Szilárd Szokolay3, Blanka Heizer1, 3, Katalin Ócsai2, Ádám Dénes4, Balázs Rózsa1, 2
1 Laboratory of 3D functional network and dendritic imaging, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
2 Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary
3 Faculty of Natural Sciences, Budapest University of Technology and Ecomonics, Budapest, Hungary
4 Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
Interictal spikes are short events of neuronal activity characteristic of epilepsy. Observed between spontaneous seizures and also during epileptogenesis, interictal spikes are believed to be caused by cells in healthy brain tissue surrounding the epileptic focus. Recent findings in animal models link interictal spikes to cognitive impairments, which is also observed in human cases. Despite its significance in epilepsy, the network mechanisms and neuronal correlates of interictal spikes are still largely unknown. In this work, we investigated the neuronal activity during interictal spikes using combined electrophysiology and two-photon calcium imaging in vivo. We induced epilepsy with a single cortical kainate microinjection in C57Bl/6J mice and injected AAV-GCaMP6f under either the syn or dlx promoter to generate a pan-neuronal or interneuron specific labeling near the kainate microinjection site. 4-6 weeks after kainate treatment, mice underwent craniotomy and electrode implantation and were subsequently imaged with two-photon resonant scanning while concurrently recording ipsilateral LFP and contralateral ECoG. We found, that mice frequenty displayed characteristic interictal spikes (but rarely seizures) with variable morphology, that reliably appeared on ipsilateral LFP but less frequenty on contralateral ECoG. We also found temporal associations between subsets of interictal spikes and neuronal and field calcium elevations, although subsets were variable even over short time periods. Overall, our approach provides an opportunity to study the underlying mechanisms of interictal spikes with two-photon imaging in vivo.