Syn III as a novel regulator of rTMS-induced emotional modulation in the prefrontal cortex under simulated space composite environment

Emotional state is a critical indicator of astronaut performance during long-duration space missions, significantly impacting both mission efficiency and post-mission adaptation to life on Earth. In this context, transcranial magnetic stimulation (TMS) may serve as a valuable tool for studying the psychological changes induced by the space environment. By combining whole-brain imaging, finite element model, cerebral blood flow imaging, genomics, and molecular validation, we tried to identify potential regulatory targets and their cofactors involved in rTMS-mediated improvement of emotional abnormalities under simulated spaceflight conditions. We identified the activation patterns of brain-wide neurons in simulated space composite environment (SSCE), particularly the reduced neuronal activity in the prefrontal cortex (PFC). rTMS could activate PFC neurons and, on a macro scale, alleviate abnormal cortical hemodynamics. Importantly, synapsin III (Syn III) is a key candidate for rTMS-mediated improvement of emotional abnormalities under SSCE, acting in coordination with proteins such as MAPK, PSD95, and NR2B. Our work not only advances the understanding of spaceflight-associated neuropsychiatric risks but also establishes a molecular framework for developing targeted neuromodulation strategies in stress-related psychiatric disorders.