Effects of Early Life Stress on Synaptic Plasticity in the Developing Hippocampus of Male and Female Rats.

Introduction: Early life stress (ELS) increases the risk for developing psychopathology in adulthood. When these effects occur is largely unknown. We here studied at which time during development ELS affects hippocampal synaptic plasticity, from early life to adulthood, in a rodent ELS model. Moreover, we investigated whether the sensitivity of synaptic plasticity to the stress-hormone corticosterone is altered by exposure to ELS.

Materials & Methods: Male and female Wistar rats were exposed to maternal deprivation (MD) for 24h on postnatal day (P)3 or left undisturbed with their mother (control). On P8-9, 22-24 and P85-95, plasma corticosterone (CORT) levels, body weight, and thymus and adrenal weights were determined to validate the neuroendocrine effects of MD. Field potentials in the CA1 hippocampus were recorded in vitro before and after high frequency stimulation. Brain slices were incubated for 20 min with 100nM CORT or vehicle 1-4h prior to high frequency stimulation, to mimic high-stress conditions in vitro.

Results & Discussion: Body weight was decreased by MD only at P4 (p = 0.02). There were minimal effects on P8-9, 22-24 or 85-95 thymus and adrenal weight and basal CORT levels. Glutamate transmission underwent strong developmental changes: half-maximal signal size strongly increased (p<0.0001) while the required half-maximal stimulation intensity concomitantly decreased with age (p = 0.04). Synaptic plasticity developed from long-term depression at P8-9 to increasing levels of long-term potentiation at later ages (p = 0.0001). MD caused a significant increase in long-term potentiation of P22-24 males (p = 0.03) and P85-95 females (p = 0.04). Bayesian modeling strongly supported the age-dependent development, with some evidence for accelerated maturation after MD in males (Bayes factor 1.23). CORT suppressed LTP in adult males; synaptic plasticity at other ages and in females remained unaffected. Thus, MD affects the development of synaptic plasticity in the CA1 hippocampus in a sex-dependent manner, with some support for the notion that maturation is accelerated in MD males.