Sex-dependent changes of hippocampal synaptic plasticity and cognitive performance in C57BL/6J mice exposed to neonatal repeated maternal separation

The repeated maternal separation (RMS) is a useful experimental model in rodents to study the long-term influence of early-life stress on brain neurophysiology. We here investigated the influence of RMS exposure on hippocampal inhibitory and excitatory synaptic transmission, long-term synaptic plasticity and the related potential alterations in learning and memory performance in adult male and female C57Bl/6J mice. Mice were separated daily from their dam for 360 min, from postnatal day 2 (PND2) to PND17, and experiments were performed at PND60. Patch-clamp recordings in hippocampal CA1 pyramidal neurons revealed a significant enhancement of GABAergic miniature IPSC (mIPSC) frequency and a decrease in the amplitude of glutamatergic mEPSCs in male mice exposed to RMS. Only a slight but significant reduction in the amplitude of GABAergic mIPSCs was observed in females exposed to RMS compared to the relative controls. A marked increase in long-term depression (LTD) at CA3-CA1 glutamatergic synapses and in the response to the CB1r agonist win55,212 were detected in RMS male but not female mice. An impaired spatial memory and a reduced preference for novelty were observed in males exposed to RMS but not in females. A single injection of -ethynyl estradiol at PND2 prevented the changes observed in RMS male mice, suggesting that estrogens may play a protective role early in life against the exposure to stressful conditions. Our findings strengthen the idea of a sex-dependent influence of RMS on long-lasting modifications in synaptic transmission, effects that may be relevant to cognitive performance

Neonatal Maternal Separation and Alcohol Abuse in C57BL/6J mice: A Study of the Functional Alterations of GABAergic and GLUergic Systems and the Possible Protective Role of Esterogen

Stress in early life may play a very important role in neurobiology of addiction developed in adulthood. In this study we investigated the effects of neonatal repeated maternal separation (RMS) on alcohol abuse in adult C57BL/6J mice and potential functional alterations of GABAergic and GLUergic systems in different brain areas. Male animals subjected to RMS consumed significantly higher amount of ethanol when compared to control counterparts. In addition, RMS is markedly associated with severe impairments in both GABAergic and GLUergic transmission that are crucial to the physiologic function of brain areas such as hippocampus and amygdala, involving learning and memory as well as fear and anxiety physiology, respectively. Interestingly females do not shown significant difference in ethanol consumption and impairments in both GABA and GLU neurotransmission, we thus studied the possible protective role showed by estrogen. Animals treated with β-ethinyl estradiol and exposed to RMS showed a similar ethanol preference when compared with controls and some of RMS-induced effect on GABA and GLU neurotransmission impairment are recovered. All together, our behavioral and electrophysiological results suggest that specific stress insult during early stage of life may markedly contribute to the onset of behavioral as well as neuropsychiatric disorders occurring in adulthood

Plasticity of GABAA receptors during pregnancy and postpartum period: From gene to function

Pregnancy needs complex pathways that together play a role in proper growth and protection of the fetus preventing its premature loss. Changes during pregnancy and postpartum period include the manifold machinery of neuroactive steroids that plays a crucial role in neuronal excitability by local modulation of specific inhibitory receptors: the GABAA receptors. Marked fluctuations in both blood and brain concentration of neuroactive steroids strongly contribute to GABAA receptor function and plasticity. In this review, we listed several interesting results regarding the regulation and plasticity of GABAA receptor function during pregnancy and postpartum period in rats. The increase in brain levels of neuroactive steroids during pregnancy and their sudden decrease immediately before delivery are causally related to changes in the expression/function of specific GABAA receptor subunits in the hippocampus. These data suggest that alterations in GABAA receptor expression and function may be related to neurological and psychiatric disorders associated with crucial periods in women. These findings could help to provide potential new treatments for these women's disabling syndromes