European Journal of Neuroscience | VOL. 56

Early‐life social stress induces permanent alterations in plasticity and perineuronal nets in the mouse anterior cingulate cortex

Publication Date Sep 30, 2022


Child maltreatment disrupts trajectories of brain development, but the underlying pathways are unclear. Stressful stimuli in early life interfere with maturation of local inhibitory circuitry and deposition of perineuronal nets (PNNs), specialized extracellular matrix structures involved in the closure of critical periods of development. Alterations in cortical PNN and parvalbumin (PV) following early-life stress (ELS) have been detected in human and animal studies. Aberrations in the anterior cingulate cortex (ACC) are the most consistent neuroimaging findings in maltreated people, but the molecular mechanisms linking ELS with ACC dysfunctions are unknown. Here, we employed a mouse model of early social threat to test whether ELS experienced in a sensitive period for ACC maturation could induce long-term aberrations of PNN and PV development in the ACC, with consequences on plasticity and ACC-dependent behavior. We found that ELS increased PNN but not PV expression in the ACC of young adult mice. This was associated with reduced frequency of inhibitory postsynaptic currents and long-term potentiation impairments and expression of intense object phobia. Our findings provide information on the long-term effects of ELS on ACC functionality and PNN formation and present evidence for a novel neurobiological pathway underlying the impact of early adversity on the brain.


Perineuronal Nets Anterior Cingulate Cortex Early-life Stress Long-term Effects Of Early-life Stress Mouse Anterior Cingulate Cortex Frequency Of Inhibitory Postsynaptic Currents Cortical Perineuronal Nets Perineuronal Nets Formation Long-term Potentiation Impairments Parvalbumin

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No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...

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