Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System

Abstract

: Although general anesthetics have been used in the clinic for more than 170 years, the ways in which they induce amnesia, unconsciousness, analgesia, and immobility remain elusive. Modulations of various neural nuclei and circuits are involved in the actions of general anesthetics. The expression of the immediate early gene c-fos and its nuclear product, c-fos protein can be induced by neuronal depolarization; therefore, 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. Identifying c-fos expression is also a direct and convenient method to explore the effects of general anesthetics on the activity of neural nuclei and circuits. Using c-fos staining, general anesthetics have been found to interact with sleep- and wakefulness-promoting systems throughout the brain, which may explain their ability to induce unconsciousness and emergence from general anesthesia. This review summarizes the actions of general anesthetics on neural nuclei and circuits based on c-fos expression.

Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain

“…Neuronal extracellular stimulation typically results in the elevation of adenosine 3’,5’-cyclic monophosphate (cAMP) levels and calcium influx, ultimately leading to the upregulation of immediate early genes (IEGs) such as c-fos ( Yap and Greenberg, 2018 ; Morgan and Curran, 1989 ). The translation product of c-fos, c-Fos protein, offers single-cell spatial resolution and has been utilized as a biomarker to identify anesthetic-activated brain regions ( Zhang et al, 2022 ). Previous investigations of c-Fos expression throughout the brain demonstrated that GABAergic agents inhibited cortical activity while concurrently activating subcortical brain regions, including VLPO, median preoptic nucleus (MEPO), lateral septal nucleus (LS), Edinger-Westphal nucleus (EW), and locus coeruleus (LC; Smith et al, 2016 ; Lu et al, 2008 ; Yatziv et al, 2020 ; Han et al, 2014 ).…”

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

“…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. Identifying c-fos expression is also a direct and convenient method to explore the effects of general anesthetics on the activity of neural nuclei and circuits.…”