Sex-dimorphic oxytocin regulation of CA1-dependent spatial memory and synaptic plasticity in juvenile rats

Research into memory mechanisms has predominantly centered on adult male rodents, often overlooking the influences of sex and developmental stage. Memory processes vary significantly between juveniles and adults, with sex acting as a critical determinant. Oxytocin (OXT) has emerged as a key modulator of fear responses and extinction in a sex-dependent manner, with prepubertal females displaying OXT-dependent contextual extinction patterns akin to adult males. These differences likely stem from diverse trajectories of hippocampal and prefrontal cortex maturation. This study examines the CA1 region's involvement in object location memory (OLM), social recognition memory (SRM), and synaptic plasticity among juvenile male and female rats, focusing on OXT's role. Results reveal that, in juvenile (postnatal day -PND 27) protein synthesis inhibition or OXT receptor blockade with OXT receptor antagonist (OXTR-Ant) in CA1 impairs OLM and impairs long-term potentiation (LTP) uniquely in males. These findings correlate with a greater increase in CA1 c-Fos expression following OLM in juvenile males compared to females. The SRM impairment was uniform across sexes under these treatments. In adults (PND 69), OXTR-Ant caused OLM impairment solely in females. These findings underscore pronounced sex- and age-specific variations in CA1-dependent memory and synaptic plasticity, shedding light on distinct neurobiological mechanisms that emerge pre-puberty and evolve throughout development.