The Impact of Anesthetic State on Spike-Sorting Success in the Cortex: A Comparison of Ketamine and Urethane Anesthesia

Abstract

Spike sorting is an essential first step in most analyses of extracellular in vivo electrophysiological recordings. Here we show that spike-sorting success depends critically on characteristics of coordinated population activity that can differ between anesthetic states. In tetrode recordings from mouse auditory cortex, spike sorting was significantly less successful under ketamine/medetomidine (ket/med) than urethane anesthesia. Surprisingly, this difficulty with sorting under ket/med anesthesia did not appear to result from either greater millisecond-scale burstiness of neural activity or increased coordination of activity among neighboring neurons. Rather, the key factor affecting sorting success appeared to be the amount of coordinated population activity at long time intervals and across large cortical distances. We propose that spike-sorting success is directly dependent on overall coordination of activity, and is most disrupted by large-scale fluctuations in cortical population activity. Reliability of single-unit recording may therefore differ not only between urethane-anesthetized and ket/med-anesthetized states as demonstrated here, but also between synchronized and desynchronized states, asleep and awake states, or inattentive and attentive states in unanesthetized animals.

Ketamine anaesthesia 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) and method of investigation (Bojak et al 2013;Hildebrandt et al 2017;Schwertner et al 2018), and emphasized the dose dependency of the observed effects (Macdonald et al 1987;Hertle et al 2016;Ahnaou et al 2017). These diverse observations have reported frequency-specific increases or decreases for beta, theta and alpha band oscillations.…”

Does Impedance Matter When Recording Spikes With Polytrodes?

“…These recordings were conducted in different brain regions and at different depths ( Supplementary Figure S2 and Supplementary Table S1 ). Also, ketamine and urethane anesthesia was used to compare noise and signal magnitude recorded during different brain states ( Hildebrandt et al, 2017 ; Figures 2E,F ). Under ketamine, the cortex switches between periods of higher neuronal activity and periods of much lower activity (up and down states) ( Ruiz-Mejias et al, 2011 ).…”

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 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). Further, spike sorting is limited under ketamine, potentially due to synchronized population dynamics across large cortical distances (Hildebrandt et al, 2017). Such synchronization has been explored in vivo through spectral analysis in various human and animal studies: at anesthetic doses, increased gamma oscillations in cortico-subcortical networks may result from an altered interplay between cortical pyramidal neurons and parvalbumin-expressing interneurons (Grent-'t-Jong et al, 2018;Lazarewicz et al, 2010;Qi et al, 2018;Slovik et al, 2017).…”