Specific and non-uniform brain states during cold perception in mice

The quest to decode the complex supraspinal mechanisms that integrate cutaneous thermal information in the central system is still ongoing. The dorsal horn of the spinal cord is the first hub that encodes thermal input which is then transmitted to brain regions via the spinothalamic and thalamo-cortical pathways. So far, our knowledge about the strength of the interplay between the brain regions during thermal processing is limited. To address this question, we imaged the brains of adult awake male mice in resting state using Functional Ultrasound imaging during plantar exposure to constant and varying temperatures. Our study, reveals for the first time: i) a dichotomy in the response of the somato-motor-cingulate cortices and the hypothalamus, which was never described before, due to the lack of appropriate tools to study such regions with both good spatial and temporal resolutions. ii) We infer that cingulate areas may be involved in the affective responses to temperature changes. iii) Colder temperatures (ramped down) reinforces the disconnection between the somato-motor-cingulate and hypothalamus networks. iv) Finally, we also confirm the existence in the mouse brain of a brain mode characterized by low cognitive strength present more frequently at resting neutral temperature. The present study points towards the existence of a common hub between somato-motor and cingulate regions, whereas hypothalamus functions are related to a secondary network. Significance Statement Very little is known regarding the brain areas involved in thermal coding and the interactions between them. Using an emerging neuroimaging technique in freely moving mice during exposure to either constant neutral / warm or cold sensation; or varying temperature. We identified dynamic brain states. Some are observed more frequently during exposure to cold stimuli. Through the demonstration of reproducible and specific fingerprints of dynamic brain modes, this study will open the path to future investigations on the alterations of these brain states during cold sensing in animal models and human subjects affected by peripheral neuropathy.