Chronic early life stress (ELS) increases vulnerability to psychopathologies and cognitive deficits in adulthood by disrupting the function of related neural circuits. However, whether this disruption emerges early in the developing brain remains largely unexplored. In the current study, using an established limited-bedding and nesting model of ELS in postnatal day (P)2-10 mice, we provide direct evidence that ELS caused early modification of hippocampal glutamatergic synapses in the developing brain. We demonstrated that ELS induced rapid enhancement of AMPA receptor function in hippocampal CA1 pyramidal neurons through a postsynaptic mechanism, and importantly, this was associated with premature unsilencing of NMDA receptor-only silent hippocampal synapses. These results suggest that potentiation of AMPAR function may represent an early mediator of ELS-induced alterations of neural networks in the developing brain and may potentially contribute to subsequent cognitive impairments later in life.NEW & NOTEWORTHY Early life stress (ELS) is known to increase the risk of later life cognitive deficits by disrupting neural circuit function. However, whether this disruption emerges early in the developing brain remains largely unexplored. The current study presents direct evidence that ELS prematurely unsilences hippocampal synapses to enhance AMPA receptor functions in a limited-bedding and nesting model, revealing an early mediator of ELS-induced neural circuit reorganizations.
Keywords: AMPA receptor; brain development; critical period; early life stress; silent synapse.