Hypercapnia-induced micro-arousals during sleep: glutamatergic mechanisms in the parabrachial nucleus.

To elucidate the neural mechanisms underlying hypercapnia triggered micro-arousal events during sleep apnea, focusing on neuronal activation and synaptic functions in medial parabrachial nucleus (MPB). Mice underwent hypercapnic challenges to induce micro-arousal events, which were recognized by cortical EEG and hippocampal local field potential (LFP) during NREM sleep. Neuronal activation was quantified via Fos immunohistochemistry in MPB. Neuronal excitability and spontaneous excitatory postsynaptic current (sEPSC) under hypercapnia in MPB slices were assessed by whole-cell patch-clamp recording. Hypercapnia was proved to trigger micro-arousal events in vivo experiment, which were characterized by rapid cortical EEG/hippocampal LFP desynchronization. We found reduced delta and theta cortical power and suppressed hippocampal gamma and ripple oscillations with elevated EMG activity after hypercapnia. Moreover, hypercapnia increased Fos expressions in MPB neurons of mice. Furthermore, in vitro experiment, hypercapnic ACSF enhanced firing frequency and increased sEPSC frequency. However, the effects were abolished by NMDA/AMPA receptor blockade in the MPB slices. The differential cortical-hippocampal spectral responses and MPB activation reveal hypercapnia effects during sleep apnea, which suggests therapeutic targets for sleep breathing-related disorders.