Brain Single Cell Transcriptomic Profiles in Episodic Memory Phenotypes Associated with Temporal Lobe Epilepsy

Abstract Memory dysfunction is prevalent in temporal lobe epilepsy (TLE), but little is known about the underlying molecular etiologies. Single-nucleus RNA sequencing technology was used to examine differences in cellular heterogeneity among left (language-dominant) temporal neocortical tissues from patients with TLE with (n = 4) or without (n = 2) impairment in verbal episodic memory. We observed marked expression heterogeneity between memory phenotypes and identified thousands of differentially expressed transcripts across all brain cell types. The most notable differences were observed in glutamatergic (excitatory) and GABAergic (inhibitory) neurons with an overrepresentation of genes associated with long-term potentiation, long-term depression, and MAPK signaling, processes known to be essential for episodic memory formation.