The Role of Hyperexcitable Existing Granule Cells in Seizure-Induced Ectopic Granule Cells

Abstract

In adult neurogenesis, where new functional neurons are generated from precursor cells, certain neurological conditions like seizures can disrupt the normal production, migration, and integration of these neurons. This disruption is characterized by ectopic granule cells (GCs) appearing in locations other than the granule cell layer, particularly following seizure-induced neurogenesis. These ectopic cells form abnormal connections and contribute to the hyperexcitability of hippocampal circuits. Although the precise molecular mechanisms behind this phenomenon remain unclear, the interplay between hyperexcitable old GCs and ectopic seizure-induced GCs is a critical factor in understanding epileptic pathology. This research proposal focuses on the hypothesis that seizure-induced neuroblasts migrate as expected but fail to connect with old GCs due to heightened excitability, resulting in abnormal connections in incorrect locations. This investigation seeks to shed light on this complex interplay and its implications for epilepsy and potential therapeutic targets.