Cerebrospinal fluid-contacting nucleus mediates the balance of depth during general anesthesia in mice

Research on the mechanisms of underlying general anesthesia has traditionally focused on specific neural circuits. In this study, we investigated the role of the cerebrospinal fluid-contacting nucleus (CSF-CN), which directly interfaces with the CSF, in modulating general anesthesia in mice.

CSF-CN was labeled by administering the retrograde tracer cholera toxin subunit B-594 into the lateral ventricle, and it was selectively ablated using a conjugate of saporin and cholera toxin subunit B. Anesthesia was induced in mice via propofol injection through the tail vein or isoflurane inhalation.

During deep anesthesia with propofol or isoflurane, mice in the CSF-CN lesion group exhibited a significantly higher burst suppression ratio compared to controls, indicating a greater depth of anesthesia. In contrast, during the emergence phase, lesion mice showed a significantly shorter latency to the recovery of the righting, reflecting premature emergence, and exhibited more severe postoperative agitation. The levels of tumor necrosis factor-α and interleukin-10 in the CSF were elevated in deep anesthesia. Behavioral assessments further revealed that mice with CSF-CN lesions displayed anxiety-like behavior after deep anesthesia.

These findings indicate that the CSF-CN plays a critical homeostatic role in general anesthesia. During deep anesthesia, it may buffer excessive anesthetic inhibition, whereas during emergence, it regulates the recovery process to prevent premature or overly rapid awakening.