Signals decline during anesthesia and rise during recovery

BF glutamate-population calcium is recorded alongside EEG and muscle activity. Signals fall rapidly after isoflurane begins, remain lower during anesthesia and rise after delivery stops.

Aligned to EEG/EMG-defined transitions, the decline begins before loss of responsiveness and the rise before recovery. Continuous changes motivate direct testing of this arousal-associated population.

Original figure 1BF population calcium changes

Optical activation accelerates righting recovery

BF glutamate optical activation shortens the interval from isoflurane cessation to righting recovery, without significantly changing time to righting loss during induction. Entry and exit respond differently to the intervention.

During concentration changes, activated mice lose righting at higher concentrations and regain it at higher concentrations. Stimulation during ongoing anesthesia also elicits movements, righting or crawling and raises behavioral arousal scores.

Original figure 2Behavioral recovery after BF optical activation

EEG shifts from slow waves toward faster activity

Under lighter anesthesia, BF activation decreases delta power and increases beta power. EEG shifts from higher-amplitude slow activity toward lower-amplitude faster activity, accompanying behavioral arousal.

Under deeper conditions, EEG alternates between bursts and suppressed periods. Activation lowers the burst-suppression ratio, which rises after stimulation ends, showing a temporally bounded cortical effect.

Original figure 3Cortical spectra and burst suppression

EEG changes need not shorten recovery time

Chemogenetic activation lowers delta power, raises theta power and reduces deeper-anesthesia burst suppression. Induction and righting-recovery times do not significantly change, distinguishing its behavioral effects from optical activation.

Chemogenetic inhibition does not significantly change induction or recovery times; optical inhibition leaves measured spectra and burst suppression unchanged. Inhibition does not necessarily reverse the effects produced by activation.

Original figure 4EEG and behavior during chemogenetic activation

Pupils and breathing change during optical activation

BF optical activation dilates pupils and increases respiratory rate in anesthetized mice. Both return toward earlier levels after stimulation, adding physiological measures to cortical and behavioral outcomes.

Pupils and breathing have distinct time courses. Concurrent observation shows that one neural intervention affects multiple responses, motivating investigation of the BF outputs involved.

Original figure 5Pupil and respiratory dynamics

Activating VTA terminals also accelerates recovery

VTA is one of several BF glutamate targets. Stimulating BF-derived terminals there shortens righting-recovery time without significantly changing induction. Concentration responses and behavioral scores also shift toward greater arousability.

During ongoing anesthesia, terminal stimulation restores righting in some animals rather than all; other responses include movements or crawling. Defined terminal stimulation modulates behavior with variable response strength.

Original figure 6Behavioral outcomes of VTA terminal activation

Terminal stimulation reproduces cortical and physiological responses

VTA terminal stimulation also decreases delta power, increases faster-band activity and reduces deep-anesthesia burst suppression. Pupils dilate and breathing accelerates before returning, paralleling BF-soma activation outcomes.

Original figure 7EEG, pupils and breathing after terminal stimulation

BF and VTA glutamate populations show linked dynamics

Dual-site recordings show linked BF and VTA glutamate calcium changes around anesthetic delivery, cessation and state transitions. BF-derived terminal stimulation increases VTA glutamate signals and shifts EEG toward faster activity.

This study including both sexes links post-isoflurane recovery with a recruitable excitatory output. Entry and exit respond asymmetrically, and EEG changes do not always accompany righting recovery, revealing more specific cellular and output contributions to emergence.

Original figure 8Simultaneous signals and VTA responses to terminal stimulation