PT  - JOURNAL ARTICLE
AU  - An, Pengying
AU  - Fang, Yue
AU  - Cheng, Yuan
AU  - Liu, Hui
AU  - Yang, Wenjing
AU  - Shan, Ye
AU  - de Villers-Sidani, Etienne
AU  - Zhang, Guimin
AU  - Zhou, Xiaoming
TI  - Acoustic enrichment prevents early life stress-induced disruptions in sound azimuth processing
AID  - 10.1523/JNEUROSCI.2287-24.2025
DP  - 2025 Mar 20
TA  - The Journal of Neuroscience
PG  - e2287242025
4099  - http://www.jneurosci.org/content/early/2025/03/21/JNEUROSCI.2287-24.2025.short
4100  - http://www.jneurosci.org/content/early/2025/03/21/JNEUROSCI.2287-24.2025.full
AB  - Early life stress (ELS) has been shown to disrupt cognitive and limbic functions, yet its impact on sensory systems, particularly the auditory system, remains insufficiently understood. In this study, we investigated the enduring effects of ELS induced by neonatal maternal separation (MS) on behavioral and cortical processing of sound azimuth in adult male rats. We found that MS significantly impairs sound-azimuth discrimination, paralleled by broader azimuth tuning and reduced dendritic branching and spine density in neurons within the primary auditory cortex. Notably, exposure to an enriched acoustic environment during the stress period effectively protects against these MS-induced alterations, restoring behavioral performance, cortical tuning, and dendritic spine density of neurons to levels comparable to controls. Further analyses reveal that epigenetic regulation of cortical brain-derived neurotrophic factor by histone H3 lysine 9 dimethylation may underlie the observed changes in cortical structure and function. These results underscore the profound and lasting impact of MS-induced ELS on auditory processing, particularly within cortical circuits involved in spatial processing. They suggest that sensory enrichment is a potential therapeutic strategy to ameliorate the adverse effects of ELS on sensory processing, with broader implications for understanding and treating sensory deficits in stress-related disorders.Significance Statement The contribution of early life stress (ELS) to sensory deficits in stress-related disorders remains largely unexplored. Here we show that ELS induced by neonatal maternal separation (MS) disrupts behavioral and cortical processing of sound azimuth in adult rats. Moreover, pairing MS with enriched acoustic exposure during the stress period alleviates these deficits in maternally separated rats. Epigenetic modulation of brain-derived neurotrophic factor gene expression by histone H3 lysine 9 dimethylation in the cortex may underlie the MS-effects and their reversal through acoustic enrichment. These findings reveal the enduring effects of ELS on sensory processing, emphasizing its broader implications for understanding stress-related disorders. Importantly, they highlight sensory enrichment as a promising therapeutic strategy to prevent sensory deficits associated with such conditions.