A deep understanding of the molecular and neural mechanisms underlying the recovery of consciousness after its loss is crucial for preventing and treating disorders of consciousness and related diseases. Professor Xue-Jun SONG of the Southern University of Science and Technology (SUSTech) has led his research team in studying consciousness and disorders of the conscious mind. The concept of consciousness has been a challenging question for centuries. Professor SONG’s team has recently published a series of studies that have systematically elucidated the molecular neural mechanisms underlying the brain’s active reboot after loss of consciousness. These studies have been published in the prestigious scientific journals, including the Nat Neurosci (2023), Pro Natl Acad Sci USA (2024), Trends Neurosci (2024), and Sci Adv (2025). They propose the “Theory of Active Reboot of Consciousness” in anesthetized brains. According to this theory, regaining consciousness involves an active reawakening process driven by intrinsic brain mechanisms rather than passive recovery following anesthetic metabolism. These findings could explain the delayed postoperative awakening and cognitive dysfunction observed in some patients.

Song’s group published a new study in Science Advances on December 5, 2025 titled “EphB1-NR2B receptor signaling in glutamatergic neurons of the ventroposteromedial thalamic nucleus regulates emergence from anesthesia.” This study expands on the molecular neural mechanisms underlying conscious reawakening and identifies the thalamic-cortical neural circuit involved in conscious reactivation. It also further refines the theory of conscious reawakening. They elucidate the critical roles of EphB1-NR2B and EphB1-KCC2 signaling in the emergence of consciousness from anesthesia and propose a two-channel collaborative mechanism. Activation of the EphB1-NR2B signaling excites the VPM-S1 glutamatergic neurons. Conversely, EphB1 activation facilitates KCC2 ubiquitin degradation, thereby disinhibiting the anesthetic inhibited neurons. The former is like pressing the gas pedal, while the latter is like pressing the brake pedal. Together, these two channels ignite the journey of consciousness recovery (Figure 1). This study further expands and improves upon the theory of the active reboot of consciousness. It also provides potential molecular and neural circuit targets for treating the neuropsychiatric diseases characterized by a loss of consciousness or other types of consciousness disorders.

Figure 1

The corresponding author of this study is Professor Xue-Jun SONG from the Medical College, and the first authors are his doctoral students Yuexin LIU (currently a physician in the Department of Anesthesiology at Zhongshan Hospital, Fudan University), Jiang-Jian HU (currently a senior postdoctoral researcher at Southern University of Science and Technology), and Boxu CAO.