GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol

Abstract

The mechanism by which general anesthetic drugs modify the state of consciousness remains unidenti ed. In essence, the Nucleus Accumbens(NAc)may be directly engaged in the principle of general anesthesia. However, it is uncertain whether NAc GABAergic neurons play a role in the propofol-induced general anesthesia effect. MethodsWe used immuno uorescence and Western blotting to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to investigate the necessity of NAc GABAergic neurons in the change of consciousness. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. ResultsWe found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. ConclusionsOur results demonstrate that NAc GABAergic neurons modulate induction and emergence of propofol anesthesia. | BackgroundGeneral anesthesia is a reversible condition of unconsciousness induced by anesthetic medications, which have been commonly used in clinical surgery for almost two hundred years [1]. Particularly, the mechanism by which general anesthetic drugs unleash the general anesthesia effect and ulteriorly modify the state of consciousness remains unidenti ed [2]. When general anesthetic drugs are applied for operations, patients frequently have adverse reactions such as low blood pressure, respiratory depression, delayed waking, and even death [3]. Additionally, cognitive dysfunction and stress disorder are likely to be continually companied by patients for a long period [4]. Unfortunately, few effective treatments exist for these debilitating illnesses, accounting for the uncertain mechanism of general anesthesia [2]. As a result,

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

“…Besides, behavioral results showed that after the stimulation, the emergence time was much longer but the induction time did not differ. These findings suggest that the nucleus accumbens GABAergic neurons regulate the progress of induction and emergence ( Yan et al, 2023 ).…”

Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction

“…According to prior experimental studies [ 32 , 33 ], chemogenetic virus was injected into the VGLUT1 mice’s CA1 region 3 weeks before anesthesia/surgery, followed by intramedullary fixation of tibial fractures. Before electrophysiological recording, immunofluorescence and behavioral tests post-anesthesia/surgery, the virus was activated by intraperitoneal injection of pre-configured Clozapine-N-oxide (CNO, Sigma-Aldrich, Saint Louis, MO, USA).…”