Tactile deprivation induces Sex-Dependent cytoarchitectural remodeling in limbic circuits and alters Anxiety-Like behavior in mice.

BACKGROUND: Sensory processing dysfunction is linked to emotional dysregulation and anxiety in humans. While tactile deprivation is known to impair dorsal hippocampal functions (spatial memory and learning), its impact on the cytoarchitecture of limbic regions central to emotional processing remains poorly understood. METHODS: Adult CD-1 mice (postnatal day 50) underwent bilateral infraorbital nerve transection (Tactile Deprivation, TD) or sham surgery. Four weeks later, anxiety-like behavior was assessed using the Open Field (OFT), Elevated Plus Maze (EPM), and Light-Dark Transition tests. Neuronal cytoarchitecture was analyzed in the ventral hippocampal CA1, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC) using Golgi-Cox staining and Sholl analysis. RESULTS: TD induced sex-dependent dendritic remodeling across all regions. In ventral CA1, TD males showed reduced proximal dendritic complexity, while TD females exhibited decreased dendritic branching. In the BLA, TD males displayed soma hypertrophy and a distal shift in dendritic complexity. In the mPFC, TD females showed reduced higher-order branching, while TD males exhibited increased distal complexity. Behaviorally, TD reduced anxiety-like behaviors in a test- and sex-specific manner: males showed reduced anxiety in the OFT, whereas females showed greater reductions in the EPM and increased exploration in the Light-Dark Transition test. Sociability did not show differences. CONCLUSION: Tactile deprivation produces sex-specific cytoarchitectural reorganization in limbic circuits, which correlates with distinct alterations in anxiety-related behaviors. These findings elucidate the role of tactile experience in shaping emotional regulation in a sexually dimorphic manner.