Cell-type-specific imaging of neurotransmission reveals a disrupted excitatory-inhibitory cortical network in isoflurane anaesthesia

Abstract

Background Despite the fundamental clinical significance of general anaesthesia, the cortical mechanism underlying anaesthetic-induced loss of consciousness (aLOC) remains elusive. Methods Here, we measured the dynamics of two major cortical neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate, through in vivo two-photon imaging and genetically encoded neurotransmitter sensors in a cell type-specific manner in the primary visual (V1) cortex. Findings We found a general decrease in cortical GABA transmission during aLOC. However, the glutamate transmission varies among different cortical cell types, where in it is almost preserved on pyramidal cells and is significantly reduced on inhibitory interneurons. Cortical interneurons expressing vasoactive intestinal peptide (VIP) and parvalbumin (PV) specialize in disinhibitory and inhibitory effects, respectively. During aLOC, VIP neuronal activity was delayed, and PV neuronal activity was dramatically inhibited and highly synchronized. Interpretation These data reveal that aLOC resembles a cortical state with a disrupted excitatory-inhibitory network and suggest that a functional inhibitory network is indispensable in the maintenance of consciousness. Funding This work was supported by the grants of the National Natural Science Foundation of China (grant nos. 81620108012 and 82030038 to H.D. and grant nos. 31922029, 61890951, and 61890950 to J.H.).

Long-term changes of parvalbumin- and somatostatin-positive interneurons of the primary motor cortex after chronic social defeat stress depend on individual stress-vulnerability

“…After another washing step (3 × 10 min), sections were incubated with a corresponding secondary antibody (Alexa Fluor ® 568, Invitrogen A-11011) at 1:500 in 0.5% Tween20 solution for 1 h at room temperature. Specificity of both primary antibodies for their targets had already been determined elsewhere ( 22 ). As a negative secondary antibody control, randomly selected sections from different mice of the cohort were stained simultaneously using the same protocol except for the primary antibody.…”

Neural Substrates for the Regulation of Sleep and General Anesthesia

“…Neocortical neuronal activity was reported to decrease by 50% under the general anesthesia induced by volatile anesthetics and by 40% with propofol and etomidate [ 126 ]. Guo et al [ 127 ] explored neurotransmission within the primary visual cortex during isoflurane anesthesia by using high-resolution approaches of in vivo two-photon imaging and genetically encoded neurotransmitter sensors. They found a general decrease in cortical GABA transmission during loss of consciousness, while glutamate transmission was mostly preserved in pyramidal cells but significantly reduced in inhibitory interneurons.…”

“…PV neuronal activity decreased slightly more than SOM interneurons, but they both were highly synchronized during the loss of consciousness. These findings depict a disrupted cortical excitatory-inhibitory network during the loss of consciousness induced by general anesthesia and emphasize the indispensable function of the inhibitory network in maintaining consciousness [ 127 ].…”

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

“…A recent study analyzed interneuron-specific intracellular Ca 2+ changes observed immediately after the loss of consciousness (Guo et al, 2021 ). VIP + interneurons showed the highest activity compared to PV + and SST + interneurons, even higher than prior to isoflurane exposure.…”