MacIver, M. B. | Search bioRxiv

bioRxiv2021

Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

BackgroundKetamine is a clinical anaesthetic and a fast-acting, long-lasting antidepressant. Ketamine is known for its antagonistic actions on N-methyl-D-aspartate (NMDA) receptors, but mechanisms leading to antidepression are not clear. The present study examined synaptic, neuronal and circuit-level loci, the duration of ketamines actions, and the involvement of NMDA receptors in these actions. MethodsExtracellular evoked field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant (10 M) and anaesthetic (350 M) concentrations. Effects of NMDA receptor antagonists, DL-2-Amino-5-phosphonovaleric acid (APV) and MK-801, {gamma}-aminobutyric acid (GABA) receptor antagonist bicuculline, and a potassium channel blocker tetraethylammonium (TEA) were also studied. ResultsKetamine decreased population spike (PS) amplitudes during application, but a long-lasting increase in PS amplitudes was seen during washout of ketamine. While the acute effects of ketamine were reversed by bicuculline, the washout increase was not altered. This long-term increase was statistically significant (p<0.01, Wilcoxon Rank Test), sustained for >2 hours, and involved postsynaptic mechanisms. A similar, long-lasting effect was produced by MK-801 but was only partially evident with APV, demonstrating the importance of channel block downstream of NMDA receptors. Furthermore, TEA produced a lasting excitability increase, indicating possible involvement of potassium channel block in ketamines long-term effects. ConclusionsThis is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anaesthesia, while increased excitatory transmission contributes to its antidepressant effects. Published AbstractsSociety for Neuroscience Annual Meeting 2019 Association of University Anesthesiologists Annual Meeting 2020 International Anesthesia Research Society Annual Meeting 2020 The Science of Consciousness Conference 2020 International Society for Anaesthetic Pharmacology Annual Meeting 2020 Western Anesthesia Residents Conference 2021 Association of University Anesthesiologists Annual Meeting 2021 International Anesthesia Research Society Annual Meeting 2021

neuroscience↗

bioRxiv2019

Complexity measures of the electroencephalograph capture loss and recovery of consciousness in patients anesthetized with propofol

Propofol is one of the most widely used anesthetics for routine surgical anesthesia. Propofol administration alone produces EEG spectral characteristics similar to most hypnotics; however, inter-individual variation can make spectral measures inconsistent. Complexity measures of EEG signals could offer universal measures to better capture anesthetic depth as brain activity exhibits nonlinear behavior at several scales. We tested the potential of nonlinear dynamics analyses to identify loss and recovery of consciousness at clinically relevant timepoints. Patients undergoing propofol general anesthesia for various surgical procedures were identified as having changes in states of consciousness by the loss and recovery of response to verbal stimuli after induction and upon cessation of anesthesia, respectively. Nonlinear dynamics analyses showed more significant differences between consciousness states than most spectral measures. Thus, complexity measures could provide a means for reliably capturing depth of consciousness based on subtle EEG changes at the beginning and end of anesthesia administration.

neuroscience↗