Fedde, S. | bioRxiv Science

bioRxiv2025

Critical Period Plasticity is Associated withResilience to Short Unpredictable Stress

Low resilience to stressful events can increase the risk of anxiety and depression. Resilience decreases with age, parallel to drastic changes in the quality of brain plasticity from juvenile to old age, suggesting that the type of plasticity found in the maturing brain promotes resilience. To indirectly test this, we administered short unpredictable stress to adult male and female wild type (WT) C57BL/6 mice, as well as to two groups of mice characterized by heightened cortical plasticity: adolescent C57BL/6 WT mice and adult mice that lack SynCAM 1 (Synaptic Cell Adhesion Molecule 1), a critical plasticity brake in the mature brain. We found that short unpredictable stress robustly increased core body temperature in all groups of mice, indicative of stress-induced hyperthermia (SIH) and confirming the efficacy of the stress paradigm. However, depressive-like behavior as measured though tail suspension test was increased in adult WT mice only, supporting that the type of plasticity found in the immature brains of adolescent WT and adult SynCAM 1 knockout (KO) mice promotes resilience to stress. All three groups of mice showed a mild increase in locomotor activity after stress, suggesting that the quality of plasticity does not correlate with resilience to anxiety-like phenotypes. Our study hence provides indirect evidence for the protective role of developmental plasticity during stress and points to new mechanisms that promote resilience to stress-induced depression.

neuroscience↗

bioRxiv2024

Adolescent-like Processing of Behaviorally Salient Cues in Sensory and Prefrontal Cortices of Adult Preterm-Born Mice

Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it is unclear how prematurity impacts circuits that support these functions. To address this, we trained adult male and female mice born a day early (preterm mice) on a visual discrimination task and found that they fail to achieve high levels of performance due to increased responding to the non-rewarded cue (false alarms). While the representation of task cues measured with in vivo electrophysiology is intact in the primary visual cortex (V1) of trained preterm mice, the representation of the non-rewarded cue is significantly weaker in regular spiking, putative pyramidal neurons in the prefrontal cortex (PFC), a brain area that mediates response inhibition. Responses to both task cues are blunted in electrophysiologically and optogenetically identified fast-spiking Parvalbumin interneurons in preterm mice, indicating impaired processing of task cues in their PFC. Indeed, single trial neuronal responses evoked by the non-rewarded cue predict the behavioral outcome more accurately in term than in preterm mice. Similar cue representation and processing is present in the PFC of adolescent term-born mice, suggesting that preterm birth impedes prefrontal maturation. Surprisingly, environmental enrichment, a well-established paradigm that promotes sensory maturation, fails to improve the performance of preterm mice. Altogether, our study describes the long-term impact of preterm birth on prefrontal and visual circuits and suggests a limited capacity of early interventions for reducing the risk of cognitive deficits after preterm birth.

neuroscience↗