Selective Activation of NAc D1R-VP/LH Circuits Promotes Reanimation From Sevoflurane Anesthesia in Mice

Abstract

BACKGROUND: Emerging evidence has uncovered a vital role of nucleus accumbens (NAc) neurons that express the dopamine D1 receptor (D1R) and its upstream neural circuit in general anesthesia (GA) regulation. However, the underlying downstream neural basis of the modulation of GA emergence by NAc D1R neurons remains unknown. In the present study, we explored the downstream neural mechanism of NAc D1R neurons in the modulation of emergence from sevoflurane GA. METHODS: We traced the axonal projections of NAc D1R neurons using a cell type-specific anterograde tracing method and immunohistochemical techniques in D1R-Cre mice. Optogenetic stimulations combined with electroencephalogram/electromyogram recordings and behavioral tests were used to determine the effects of optogenetic activation of the axonal terminals of NAc D1R neurons on sevoflurane emergence during sevoflurane-induced continuous, steady-state general anesthesia (CSSGA) or burst-suppression oscillations. RESULTS: Labeled efferent fibers of NAc D1R neurons were highly distributed in the ventral pallidum (VP), lateral hypothalamus (LH), and substantia nigra pars compacta. Optogenetic activation of the NAc D1R -VP circuit during CSSGA with sevoflurane induced cortical activation (mean ± standard deviation [SD]; delta power: prestimulation versus during stimulation, 48.7% ± 5.7% vs 35.1% ± 3.3%, P < .0001; beta power: 7.1% ± 2.7% vs 14.2% ± 3.3%, P = .0264) and behavioral emergence, and restored the righting reflex in 66.7% of ChR2 mice. Optogenetic stimulation of the NAc D1R -LH circuit also produced cortical activation (delta power: prestimulation versus during stimulation, 45.0% ± 6.5% vs 36.1% ± 4.6%, P = .0016) and behavioral emergence, and restored the righting reflex in 100% of the ChR2 mice during CSSGA with sevoflurane. Under a sevofluraneinduced burst-suppression state, NAc D1R -VP/LH circuit activation produced evidence of cortical activation (burst-suppression ratio [BSR]: NAc D1R -

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice

“…Research has indicated that EEG delta (0.5-4 Hz) power gradually increases from the state of awakening to anesthesia [20]. The results showed a significant reduction in the time to ROC in the caspase-3-mediated ablation group of mice, from 690 (72) s to 520 (48) s (p = 0.02) (Figure 3A,B,D). This was accompanied by a decrease in the proportion of delta waves during the emergence period, from 29.2 (1.5) % to 24.0 (1.1) % (p = 0.039) (Figure 3A,B,E,F).…”

“…Immunofluorescence was performed as described previously [ 20 , 48 ]. The mice were deeply anesthetized with pentobarbital sodium and intracardially perfused with phosphate-buffered saline (PBS), followed by 4% paraformaldehyde (PFA) in PBS.…”

Recent advances in neural mechanism of general anesthesia induced unconsciousness: insights from optogenetics and chemogenetics

“…Furthermore, EEG spectral analysis showed that optogenetic inhibition induced an increase in beta waves during the induction period, and a significantly increased delta waves and a decreased alpha, beta and gamma waves during the emergence period ( Zhang J. et al, 2023 ). Bao et al also found that optogenetic activation of the terminals of the nucleus accumbens dopamine D1 receptor-expressing neurons in the ventral pallidum induced cortical activation and behavioral emergence ( Bao et al, 2023 ).…”

“…Under deep anesthesia, optogenetic activation of these neurons changed the EEG pattern from the burst suppression to a relatively active state with low amplitude and high frequency waves. In addition, the BSR of ChR2 mice decreased significantly during optical stimulation ( Bao et al, 2023 ). Overall, these results suggest that the nucleus accumbens dopamine D1 receptor-expressing neurons has a modulatory effect on the induction and emergence processes of sevoflurane anesthesia.…”

Dopamine D2-receptor neurons in nucleus accumbens regulate sevoflurane anesthesia in mice

“…In a study by Oishi et al (2017) optogenetic activation of NAc neuronal terminals within the VP was found to decrease the firing rate of VP neurons and induce inhibitory postsynaptic currents, a phenomenon not observed in other downstream nuclei of the NAc. Furthermore, Bao et al (2023) reported that the activation of the NAc D1 R -VP pathway could facilitate the recovery of mice from sevoflurane anesthesia. These studies collectively demonstrate the close relationship between the NAc and VP, as well as their ability to regulate the process of general anesthesia.…”