Manipulating Neural Circuits in Anesthesia Research

Abstract

The neural circuits underlying the distinct endpoints that define general anesthesia remain incompletely understood. It is becoming increasingly evident, however, that distinct pathways in the brain that mediate arousal and pain are involved in various endpoints of general anesthesia. To critically evaluate this growing body of literature, familiarity with modern tools and techniques used to study neural circuits is essential. This Readers’ Toolbox article describes four such techniques: (1) electrical stimulation, (2) local pharmacology, (3) optogenetics, and (4) chemogenetics. Each technique is explained, including the advantages, disadvantages, and other issues that must be considered when interpreting experimental results. Examples are provided of studies that probe mechanisms of anesthesia using each technique. This information will aid researchers and clinicians alike in interpreting the literature and in evaluating the utility of these techniques in their own research programs.

Prefrontal Cortex Metabolome Is Modified by Opioids, Anesthesia, and Sleep

“…During isoflurane anesthesia the four-transmitter network fractionated into two different networks, one of which comprised only GABA and glutamate. During wakefulness and during isoflurane anesthesia, the most highly correlated neurotransmitters were those shown by many laboratories to contribute to generating and maintaining wakefulness (74,105,106).…”

The brain rhythms that detach us from reality

“…Vesuna and colleagues' work exemplifies how these advances are enabling investigators to probe the nature of consciousness itself. They are also revolutionizing the science of anaesthesiology 5 -allowing investigators to better understand how anaesthetics produce unconsciousness 6 , how these mechanisms overlap with natural sleep 7 , and how people recover consciousness after anaesthesia 8 . Research into consciousness and anaesthesia overlaps, too, because anaesthetics provide a powerful, reliable means of eliciting reversible states of altered consciousness.…”

“…Unfortunately, such molecules often have to be synthesized from scratch using long, highly customized sequences of reactions that are prohibitively slow and impractical at large scales. Li et al 5 report on page 145 how a modular synthesis of the structurally complex antibacterial compound virginiamycin M2 (VM2), based on easily interchangeable molecular building blocks, has provided access to VM2 derivatives that could not previously have been prepared -and has thereby enabled the rational development of a variant that evades an ancient resistance mechanism.…”

Brain areas modulation in consciousness during sevoflurane anesthesia

“…By precisely modulating the neurons in particular brain regions, optogenetics, chemogenetics, and electrical stimulation can aid researchers in better understanding the function of brain regions in regulating consciousness while investigating brain regions related to anesthesia. These techniques can target a particular type of neuron or glial cell and investigate how it regulates anesthesia (Melonakos et al, 2020 ).…”