Abstract
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.
Footnotes
We thank Christoph Schreiner, Jufang He, and Robert Froemke for their helpful discussions on earlier versions of this paper. X.Z. receives funding from the National Science and Technology Innovation 2030 Major Program (2022ZD0204804), the National Natural Science Foundation of China (32161160325, 32171134, 32471059), the Joint Fund for Medicine and Health from the ECNU (2022JKXYD08001), and the matching fund from the NYU-ECNU Institute of Brain and Cognitive Science at the NYU Shanghai.
The authors declare no competing interests.
↵*These authors have contributed equally to this work
