An Age Dependent Seizure Vulnerability of Hippocampal CA2: Finding the Targets to Rescue Seizure-Induced Social Recognition Memory Deficits

Abstract

Early life seizures (ELS) pose a significant threat to developing neurons and often result in later-life epilepsy and cognitive deficits, including social cognition deficits. Hippocampal CA2 has recently emerged as a critical region in processing social recognition memory. Little is known about the effects of ELS on CA2 pyramidal neurons in the developing hippocampus. Here, using established ELS models, we demonstrated that ELS impaired social recognition memory in mouse pups. We showed that unlike the adult CA2 neurons, ELS significantly activated CA2 neurons in p10 mice. Interestingly, ELS selectively enhanced AMPA receptor function in the activated CA2 neurons in the immature brain . Using a unique actviatiy-dependent labeling and manipulating system, c-Fos-GFP/c-Fos-tTA/TRE-hM4Di mouse model, we discovered that precisely suppressing ELS-activated neurons rescued ELS-induced AMPAR function enhancement in CA2 neurons and social recognition memory deficits. Our results identify the novel cellular target of ELS for potential intervention of ELS-induced cognitive deficits.