Abstract

Epilepsy is a multi-etiological brain dysfunction syndrome. Hippocampal neuronal damage induced by seizures may be one of the causes leading to cognitive impairment, but the underlying mechanism remains to be further elucidated. The kainic acid (KA) model of temporal lobe epilepsy is widely used in understanding of the epileptogenesis. Fiber photometry is a signal detection technology suitable for recording calcium activity of neurons in the deep brain of freely moving animal. Here, we used the optical fiber-based method to monitor the real-time neuronal population activities of freely moving mice after subcutaneous injection of KA. We observed that KA administration led to one to three kinds of stereotypical patterns of epileptiform calcium activity in CA1, CA3, and dentate gyrus (DG) of the hippocampus, as well as the entorhinal cortex (EC). There were three kinds of waves in the hippocampal CA1, which we named wave 1, wave 2 and slow flash. Wave 1 and wave 2 appeared in both the CA3 and DG regions, but the EC only showed wave 1. In these epileptiform calcium signals, we observed a high amplitude and long duration calcium wave as a part of wave 2, which resembled cortical spreading depression (CSD) and always appeared at or after the end of seizure. Because the same characteristic of epileptiform calcium signal appeared in different brain regions, calcium signal may not exist with region specificity, but may exhibit a cell type specific manner. Thus, our work provides a support for the pathogenesis of epilepsy and epileptiform signal transmission research.

Highlights

  • Epilepsy is a multi-etiological brain dysfunction syndrome, affecting almost 70 million people around the world[1]

  • We combined well established assessments of seizure activity such as Racine rules[16] with functional calcium signals recording of calcium indicator Oregon green 488 BAPTA-1 AM (OGB-1 AM) in the hippocampal CA1, CA3, dentate gyrus (DG) and entorhinal cortex (EC) in freely behaving mice subcutaneously administrated of kainic acid (KA)

  • We stained with the calcium indicator OGB-1AM in hippocampal CA1, CA3, DG or EC and applied the optical fiber-based approach to record population calcium activity

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Summary

Introduction

Epilepsy is a multi-etiological brain dysfunction syndrome, affecting almost 70 million people around the world[1]. The calcium hypothesis of epilepsy[4] points out that when the intracellular calcium concentration is beyond the normal level, yet dose not reach the extent of calcium overload to generate excitotoxicity, the abnormal increase of calcium concentration may cause transient or persistent changes in neural plasticity. These neuronal pathological changes, in the long run, may results in abnormal discharge of neurons which causes epilepsy. Calcium recording based on fiber photometry has the advantage of recording in deep brain regions of freely behaving mice, with small physical damage to brain tissue and simple experimental operation[17,18]

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