State-dependent neuronal and network dynamics in the lateral hypothalamus across sevoflurane anesthesia–emergence revealed by microelectrode arrays

General anesthetics can induce a safe, reversible state of unconsciousness, yet their neural mechanisms remain incompletely understood. The lateral hypothalamus (LH) contains orexinergic and other arousal-promoting neurons and projects broadly to anesthesia-arousal-related nuclei such as the ventral tegmental area (VTA) together with locus coeruleus (LC), being critically involved in anesthetic-induced loss of consciousness. However, high spatiotemporal-resolution in vivo evidence characterizing the dynamic electrophysiological features of LH during the anesthesia-emergence transition is lacking. To fill this gap, we developed multi-channel microelectrode arrays and optimized the electrode surface using PtNPs/PEDOT:PSS to lower impedance and improve signal-to-noise ratio. Under a mouse paradigm spanning wakefulness, sevoflurane anesthesia, and post-anesthetic emergence, we simultaneously recorded, in vivo, cortical electroencephalography (EEG), local field potentials (LFPs), and single-unit activity (spikes) within the LH. At the single-neuron level, 78% of LH neurons were suppressed during anesthesia, exhibiting distinct and recognizable spike waveform features, whereas 11% were activated and 11% remained unchanged. In a subset of suppressed and activated units, spike amplitude varied in parallel with firing rate under sevoflurane. At the population level, sevoflurane produced low-frequency-dominated spectra accompanied by elevated spectral edge frequency (SEF95) in both cortical EEG and LH LFPs; the LH displayed a higher fraction of delta power, whereas EEG showed larger SEF95 shifts relative to wake, suggesting greater cortical sensitivity to anesthetic depth while the LH exhibited more pronounced synchrony. Moreover, sevoflurane anesthesia was associated with a state-dependent enhancement of low-frequency functional coupling between LH LFPs and cortical EEG, which was reversible upon emergence. Collectively, these findings delineate a multi-scale electrophysiological profile of the LH across anesthesia-emergence and lay the groundwork for elucidating the circuit mechanisms through which inhaled anesthetics lead to loss of consciousness.