IMPACT OF PRENATAL STRESS ON SOCIAL BEHAVIOR AND SENSORY INTEGRATION MEDIATED BY DISRUPTED PLEASANT TOUCH PROCESSING IN ADULT MICE

Prenatal stress (PS) is a major environmental risk factor for neurodevelopmental disorders and is associated with long-lasting alterations of emotional, sensory, and social functions. Pleasant touch, a component of affective touch that promotes social bonding, is encoded by C-low threshold mechanoreceptors (C-LTMRs), peripheral neurons tuned to gentle, caressing stimuli.This study aimed to determine whether PS alters C-LTMR properties and whether modulation of the pathway engaged by C-LTMRs can influence PS-induced social deficits.
First, to determine whether affective touch processing is altered by prenatal stress, we assessed pleasant touch perception in a place preference conditioning paradigm using gentle brushing. Control mice developed a preference for the brush-paired compartment, whereas PS mice did not, indicating impaired processing of pleasant touch. We then measured behavioral alterations in adulthood. Using the Live Mouse Tracker to measure social interactions in a naturalistic context, PS offspring showed marked sociability deficits, while complementary sensory assays revealed tactile hypersensitivity. To identify potential peripheral mechanisms underlying these behavioral deficits, we characterized C-LTMRs at anatomical, molecular, and functional levels. PS induced consistent alterations across all measured levels, indicating altered sensory encoding. Together, these changes indicate disrupted C-LTMR function. Finally, to test whether modulation of affective touch pathways could rescue social deficits, we chemogenetically activated peripheral Tyrosine Hydroxylase-positive sensory neurons, including C-LTMRs, which restored social preference in PS mice.
Together, these findings show that prenatal stress impacts pleasant touch pathways and that peripheral sensory dysfunction could drive long-lasting social deficits, suggesting C-LTMRs as a target to improve social behavior.