Isoflurane and ketamine differentially influence spontaneous and evoked laminar electrophysiology in mouse V1

Abstract

General anesthesia is ubiquitous in research and medicine, yet although the molecular mechanisms of anesthetics are well characterized, their ultimate influence on cortical electrophysiology remains unclear. Moreover, the influence that different anesthetics have on sensory cortices at neuronal and ensemble scales is mostly unknown, and represents an important gap in knowledge that has widespread relevance for neural sciences. To address this knowledge gap, this work explored the effects of isoflurane and ketamine/xylazine, two widely used anesthetic paradigms, on electrophysiological behavior in mouse primary visual cortex. First, multiunit activity and local field potentials were examined to understand how each anesthetic influences spontaneous activity. Then, the inter-laminar relationships between populations of neurons at different cortical depths were studied to assess whether anesthetics influenced resting-state functional connectivity. Lastly, the spatiotemporal dynamics of visually evoked multiunit and local field potentials were examined to determine how each anesthetic alters communication of visual information. We found that isoflurane enhanced the rhythmicity of spontaneous ensemble activity at 10-40 Hz, which coincided with large increases in coherence between layer IV with superficial and deep layers. Ketamine preferentially increased local field potential power from 2-4 Hz, and the largest increases in coherence were observed between superficial and deep layers. Visually evoked responses across layers were diminished under isoflurane, and enhanced under ketamine anesthesia. These findings demonstrate that isoflurane and ketamine anesthesia differentially impact sensory processing in V1.

A wrappable microwire electrode for awake, chronic interfacing with small diameter autonomic peripheral nerves

“…Developing a neural interface model in mice is critical due to the availability of transgenic and disease models, thus increasing the impact for future studies untangling mechanisms of various diseases. A focus was also placed on awake, non-anesthetized recordings, since anesthesia is known to alter neural activity (Brown et al 2010;Michelson & Kozai 2018;Uhrig et al 2018) and adjusting the isoflurane concentration can significantly impact vagus nerve activity (Silverman et al 2018). Therefore, to increase spontaneous neural activity and to better model the clinical environment, an awake recording paradigm was developed.…”

Spreading depressions and periinfarct spreading depolarizations in the context of cortical plasticity

“…(IIIA). The ECoG pattern was normal, similar to isoflurane anesthesia in rats (Michelson and Kozai, 2018) oscillations showed no significant differences between these groups. SDs and PiDs frequency (SDs: 3.8 ±1.9 Hz, PiDs: 2.9±1.3 Hz) and the amplitude from the baseline (SDs: 0.47±0.2 mV, PiDs: 0.48±0.5 mV) and the area below the depolarization wave were similar.…”

Ketamine anesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

“…Previous findings investigating ketamine in vivo have described differential effects based on brain region (Slovik et al, 2017;Widman & McMahon, 2018), method of investigation (Bojak et al, 2013;Hildebrandt et al, 2017;Schwertner et al, 2018), and emphasized the dose dependency of the observed effects (Ahnaou et al, 2017;Hertle et al, 2016;Macdonald et al, 1987). These diverse observations have reported frequency-specific increases or decreases also for the beta, theta and alpha band.…”

“…One commonly used surgical anesthetic in systems physiology is ketamine-an N-methyl-D-aspartate (NMDA) receptor antagonist-which enters the open receptor channel inhibiting ionic exchange (Anis et al, 1983;Macdonald et al, 1987). One main effect of ketamine thereby is a persistent increase in cortical glutamate which renders cells more excitable (Miller et al, 2016;Zhang et al, 2019) and disinhibition of the cortex through suppression of GABAergic interneurons (Behrens et al, 2007;Homayoun & Moghaddam, 2007;Schobel et al, 2013).…”