Regulation of Neural Circuitry under General Anesthesia: New Methods and Findings

Abstract

General anesthesia has been widely utilized since the 1840s, but its underlying neural circuits remain to be completely understood. Since both general anesthesia and sleep are reversible losses of consciousness, studies on the neural-circuit mechanisms affected by general anesthesia have mainly focused on the neural nuclei or the pathways known to regulate sleep. Three advanced technologies commonly used in neuroscience, in vivo calcium imaging, chemogenetics, and optogenetics, are used to record and modulate the activity of specific neurons or neural circuits in the brain areas of interest. Recently, they have successfully been used to study the neural nuclei and pathways of general anesthesia. This article reviews these three techniques and their applications in the brain nuclei or pathways affected by general anesthesia, to serve as a reference for further and more accurate exploration of other neural circuits under general anesthesia and to contribute to other research fields in the future.

Selective optogenetic modulation of the PBN terminals in the lateral hypothalamic area and basal forebrain regulates emergence from isoflurane anesthesia in mice

“…Since the loss of consciousness is a fundamental aspect shared by both sleep and general anesthesia, it has been proposed that these two states have overlapping neural endpoints. Research has demonstrated that the reversible loss and recovery of consciousness induced by anesthetics result from the precise regulation of various arousal or sleep nuclei [ 26 ].…”

Selective optogenetic modulation of the PBN terminals in the lateral hypothalamic area and basal forebrain regulates emergence from isoflurane anesthesia in mice

“…It has been successfully combined with behavioral paradigms in animals to investigate the role of speci c subtypes of neurons or their afferent/efferent circuits in various brain functions. For example, it has been used to study cognition-related neurons in the locus coeruleus nucleus [23] and depression responsive medium spiny neurons in the NAc [24]. Given the rapid transitions between anesthesia states, we utilized this technique to explore the downstream systems regulated by the PBN.…”

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

“…Optogenetics can precisely regulate the temporal accuracy of specific neurons or neural circuits ( Zhang et al, 2022 ). Opsins are usually introduced into neurons in the target region by injection of virus that contains the opsin gene, and experiments are performed approximately 3 weeks later.…”

“…It is becoming increasingly evident that many of the neural circuits involved in the sleep–wake cycle are also relevant for general anesthesia. ( Zhang et al, 2022 ; Espinosa-Juárez et al, 2023 ). Studying neural networks necessitates the utilization of advanced techniques for neural labeling and modulation, including optogenetics, chemogenetics, electrophysiology, calcium imaging, anterograde/retrograde tracing behavioral testing, and so on.…”