Senmiao Sun

All Publications

• Striatum supports fast learning but not memory recall NATURE Reinhold, K., Iadarola, M., Tang, S., Chang, A., Kuwamoto, W., Albanese, M. A., Sun, S., Hakim, R., Zimmer, J., Wang, W., Sabatini, B. L. 2025; 643 (8071): 458-467

  Abstract

  Animals learn to carry out motor actions in specific sensory contexts to achieve goals. The striatum has been implicated in producing sensory-motor associations1, yet its contributions to memory formation and recall are not clear. Here, to investigate the contribution of the striatum to these processes, mice were taught to associate a cue, consisting of optogenetic activation of striatum-projecting neurons in visual cortex, with the availability of a food pellet that could be retrieved by forelimb reaching. As necessary to direct learning, striatal neural activity encoded both the sensory context and the outcome of reaching. With training, the rate of cued reaching increased, but brief optogenetic inhibition of striatal activity arrested learning and prevented trial-to-trial improvements in performance. However, the same manipulation did not affect performance improvements already consolidated into short-term (less than 1 h) or long-term (days) memories. Hence, striatal activity is necessary for trial-to-trial improvements in performance, leading to plasticity in other brain areas that mediate memory recall.

  View details for DOI 10.1038/s41586-025-08969-1

  View details for Web of Science ID 001483463300001

  View details for PubMedID 40335692

  View details for PubMedCentralID PMC12244412

• A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan. Nature aging Jayne, L., Lavin-Peter, A., Roessler, J., Tyshkovskiy, A., Antoszewski, M., Ren, E., Markovski, A., Sun, S., Yao, H., Sankaran, V. G., Gladyshev, V. N., Brooke, R. T., Horvath, S., Griffith, E. C., Hrvatin, S. 2025

  Abstract

  Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes.

  View details for DOI 10.1038/s43587-025-00830-4

  View details for PubMedID 40055478

• Neurons that regulate mouse torpor NATURE Hrvatin, S., Sun, S., Wilcox, O. F., Yao, H., Lavin-Peter, A. J., Cicconet, M., Assad, E. G., Palmer, M. E., Aronson, S., Banks, A. S., Griffith, E. C., Greenberg, M. E. 2020; 583 (7814): 115-+

  Abstract

  The advent of endothermy, which is achieved through the continuous homeostatic regulation of body temperature and metabolism1,2, is a defining feature of mammalian and avian evolution. However, when challenged by food deprivation or harsh environmental conditions, many mammalian species initiate adaptive energy-conserving survival strategies-including torpor and hibernation-during which their body temperature decreases far below its homeostatic set-point3-5. How homeothermic mammals initiate and regulate these hypothermic states remains largely unknown. Here we show that entry into mouse torpor, a fasting-induced state with a greatly decreased metabolic rate and a body temperature as low as 20 °C6, is regulated by neurons in the medial and lateral preoptic area of the hypothalamus. We show that restimulation of neurons that were activated during a previous bout of torpor is sufficient to initiate the key features of torpor, even in mice that are not calorically restricted. Among these neurons we identify a population of glutamatergic Adcyap1-positive cells, the activity of which accurately determines when mice naturally initiate and exit torpor, and the inhibition of which disrupts the natural process of torpor entry, maintenance and arousal. Taken together, our results reveal a specific neuronal population in the mouse hypothalamus that serves as a core regulator of torpor. This work forms a basis for the future exploration of mechanisms and circuitry that regulate extreme hypothermic and hypometabolic states, and enables genetic access to monitor, initiate, manipulate and study these ancient adaptations of homeotherm biology.

  View details for DOI 10.1038/s41586-020-2387-5

  View details for Web of Science ID 000623830500002

  View details for PubMedID 32528180

  View details for PubMedCentralID PMC7449701