Understanding the Effects of General Anesthetics on Cortical Network Activity Using Ex Vivo Preparations

Abstract

General anesthetics have been used to ablate consciousness during surgery for more than 150 yr. Despite significant advances in our understanding of their molecular-level pharmacologic effects, comparatively little is known about how anesthetics alter brain dynamics to cause unconsciousness. Consequently, while anesthesia practice is now routine and safe, there are many vagaries that remain unexplained. In this paper, the authors review the evidence that cortical network activity is particularly sensitive to general anesthetics, and suggest that disruption to communication in, and/or among, cortical brain regions is a common mechanism of anesthesia that ultimately produces loss of consciousness. The authors review data from acute brain slices and organotypic cultures showing that anesthetics with differing molecular mechanisms of action share in common the ability to impair neurophysiologic communication. While many questions remain, together, ex vivo and in vivo investigations suggest that a unified understanding of both clinical anesthesia and the neural basis of consciousness is attainable.

Cholinergic modulation inhibits cortical spreading depression in mouse neocortex through activation of muscarinic receptors and decreased excitatory/inhibitory drive

“…Notably, anesthetics can induce in vivo slow rhythmic activity, including cortical UP/DOWN states, and some of them can inhibit CSD, although there are controversial reports about their effect on CSD (Klass et al, 2018). Similar to cholinergic modulations, anesthetics show complex mechanisms and some of them can reduce neuronal network excitability in the neocortex (Becker et al, 2012;Voss et al, 2019).…”

Cortical functional connectivity indexes arousal state during sleep and anesthesia

“…Although endogenous sleep and arousal centers play a role in LOC/ROC under both sleep and anesthesia (Lydic and Baghdoyan, 2005), changes in the contents of consciousness are likely secondary to actions in neocortex (Voss et al, 2019), which is the focus of the current study. Common mechanisms for LOC/ROC under sleep and anesthesia are suggested by similar effects of LOC on sensory cortex observed under both conditions.…”

Anesthesia and sleep disorders – a new problem in modern anesthesiology (literature review)

“…Системний рівень забезпечується топографічною реорганізацією обміну інформації, руйнуванням позитивних зв'язків між локальним та системним рівнями обміну інформацією з перериванням переважно у вузлових ділянках мереж мозку [23]. При цьому пригнічення функціонування таламокортикальних шляхів більш характерне для пропофолу та севофлюрану, в той час як кетамін переважно діє на потиличні частки передфронтоцентральних ділянок кори [24,25]. Крім того, в останніх дослідженнях виявлено специфічні нейрони, активовані загальною анестезією (General-anesthesia-activated neurons -AANs) -група нейроендокринних клітин поблизу супраоптичного ядра, які активуються під час загальної анестезії за допомогою будь-яких анестетиків.…”