Sex-dependent changes of hippocampal synaptic plasticity and cognitive performance in C57BL/6J mice exposed to neonatal repeated maternal separation. (1st January 2023)

• Record Type: Journal Article
• Authors: Talani, Giuseppe; Biggio, Francesca; Gorule, Ashish Avinash; Licheri, Valentina; Saolini, Eleonora; Colombo, Daniele; Sarigu, Gabriele; Petrella, Michele; Vedele, Francescangelo; Biggio, Giovanni; Sanna, Enrico
• Is Part Of: Neuropharmacology. Volume 222(2023)
• Publication Date: 2023-01-01
• Subjects: Maternal separation -- Stress -- Neuronal plasticity -- GABA -- CB1r -- Cognition -- Glutamate; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109301
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: The repeated maternal separation (RMS) is a useful experimental model useful 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 PND 60. 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 was observed in males exposed to RMS but not in females. A single injection of β-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 for cognitive performance. Highlights: The repeated maternal separation causes a significant unbalance between GABAergic and glutamatergic transmission in male but not in female mice. RMS alters long-term depression at CA3-CA1 glutamatergic synapses and response to CB1r agonist in males but not in females. RMS impairs spatial memory and reduces preference for novelty in male mice exposed to RMS but not in females. A single injection of b-ethynyl estradiol at PND2, prevented in males the changes induced by RMS.