AbstractPrenatal stress (PS) can impact fetal brain structure and function and lead to higher vulnerability to neurodevelopmental and neuropsychiatric disorders. To understand how PS alters evoked and spontaneous cortical activity and intrinsic brain functional connectivity, mesoscale voltage imaging was performed in adult C57BL/6NJ mice who were exposed to an auditory stress paradigm on gestational days 12-16. PS mice demonstrated a four-fold higher basal corticosterone level, reduced amplitude of all cortical sensory-evoked responses (visual, auditory, whisker, forelimb, and hindlimb), decreased overall resting-state functional connectivity, declined network efficiency, reduced inter-module connectivity, enhanced intra-module connectivity, and altered frequency of auditory and forelimb spontaneous sensory motifs relative to control animals. In fact, for PS, the resting-state functional connectivity changes drastically towards an overall less connected structure that consists of largely disjoint but tight modules, leading to a declined network efficiency. The changes in structure also indicate that the posterior secondary motor, primary barrel, and secondary hindlimb cortices are cortical areas with higher susceptibility to dysfunction. Our findings highlight the PS modulation of brain functional connectivity that can pose offspring at risk for stress-related neuropsychiatric disorders.
Prenatal stress dysregulates resting-state functional connectivity and sensory motifs
