Effects of General Anesthetics on Synaptic Transmission and Plasticity

Abstract

: General anesthetics depress excitatory and/or enhance inhibitory synaptic transmission principally by modulating the function of glutamatergic or GABAergic synapses, respectively, with relative anesthetic agent-specific mechanisms. Synaptic signaling proteins, including ligand- and voltage-gated ion channels, are targeted by general anesthetics to modulate various synaptic mechanisms including presynaptic neurotransmitter release, postsynaptic receptor signaling, and dendritic spine dynamics to produce their characteristic acute neurophysiological effects. As synaptic structure and plasticity mediate higher-order functions such as learning and memory, long-term synaptic dysfunction following anesthesia may lead to undesirable neurocognitive consequences depending on specific anesthetic agent and the vulnerability of population. Here we review the cellular and molecular mechanisms of transient and persistent general anesthetic alterations of synaptic transmission and plasticity.

Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review

“…Although general anesthetics are clinically invaluable for their reversible short-term effects on consciousness, evidence is accumulating that they also have the potential to induce neuronal plasticity and long-term changes in cognitive function (Vutskits, 2012 ; Platholi and Hemmings, 2021 ). These outcomes appear steeply dependent not just on drug regime but also on human and animal model properties, e.g., clinical condition, age, surgical treatment, etc.…”

Progress in Neuropharmacology of Anesthetics and Analgesics for the Improvement of Medical Treatment

“…In the review by Daniel Mulkey et al [ 3 ], the authors comprehensively discuss the contributions of astrocyte in general anesthesia, which is a recently identified modulator in the central nervous system that is involved in the action of general anesthetics [ 4 ]. In the review by Platholi and Hemmings [ 5 ], the authors review the cellular and molecular mechanisms of transient and persistent general anesthetic alterations of synaptic transmission and plasticity, which is critically important to higher-order brain functions such as learning and memory in general anesthesia. For the review by Donghang Zhang et al [ 6 ], c-fos staining is commonly used to identify the activated neurons during sleep and/or wakefulness, as well as in various physiological conditions in the central nervous system.…”

Tranexamic acid-associated fatal status epilepticus in a paediatric patient

“…GABAA receptor modulation by propofol has distinct dose-dependent effects likely involving multiple sites of action; clinical concentrations of propofol potentiate GABA-activated currents, increase open channel frequency, and reduce the rate of desensitization, while intermediate concentrations directly activate GABAA channels, and even higher concentrations inhibit receptor function. 4 Propofol can cause neuroexcitatory effects, including tonic-clonic seizures, particularly during the start or weaning from propofol infusion. 5 Among the various mechanisms that have been proposed for these neuroexcitatory symptoms are antagonism of glycine and dopamine receptors, hyposensitization of GABAergic pathways and dysregulated inhibition of NMDA glutamate receptors.…”