Propofol anesthesia concentration rather than abrupt behavioral unresponsiveness linearly degrades responses in the rat primary auditory cortex

Abstract

Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration versus behavioral unresponsiveness, which are typically confounded. Here, we used slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural electroencephalogram, and neuronal spiking activity in primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, postonset neuronal silence duration, late-locking to 40 Hz click-trains, and offset responses, gradually changed in a dose-dependent manner with increasing anesthesia levels without showing abrupt shifts around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences.

Sleep-like changes in neural processing emerge during sleep deprivation in early auditory cortex

“…During deep anesthesia, responses to high-frequency stimuli are attenuated in cat visual cortex (Rager, 1998) and in rodent somatosensory (Castro-Alamancos, 2004) and auditory cortex (Marguet and Harris, 2011). In natural sleep and light propofol anesthesia, auditory cortex of both rodents and humans reveals reduced responses to 40Hz click-trains (Bergman et al, 2022;Hayat et al, 2021;Krom et al, 2020), as has been originally observed with scalp EEG (Lustenberger et al, 2017;Plourde, 1990). Here, we extend these results to show that already during wakefulness, SD-induced Tired conditions entail sensory adaptation at significantly lower frequencies, acting like a low-pass filter that quenches high-frequency neural inputs and diminishes rapid transmission of information across brain regions.…”

“…The copyright holder for this preprint this version posted March 7, 2022. ; https://doi.org/10.1101/2022.03.06.483154 doi: bioRxiv preprint sleep (Bergman et al, 2022;Wang, 2011, 2013;Krom et al, 2020;Nir et al, 2013a;Nourski et al, 2018;Raz et al, 2014;Sela et al, 2020). In this context, SD affords an additional unique window to examine how brain states affect sensory processing by offering a 'middle-tier' alternative -a state where subjects are awake and responsive but already show behavioral deficits (Krause et al, 2017;Lim and Dinges, 2010).…”

“…A second approach focuses on momentary changes in arousal, indexed by pupil size, EEG or locomotor activity during wakefulness (Bereshpolova et al, 2011; Lin et al, 2019; McGinley et al, 2015; Zhou et al, 2014; Zhuang et al, 2014). The third strategy contrasts sensory processing in wakefulness with those during anesthesia or natural sleep (Bergman et al, 2022; Issa and Wang, 2011, 2013; Krom et al, 2020; Nir et al, 2013a; Nourski et al, 2018; Raz et al, 2014; Sela et al, 2020). In this context, SD affords an additional unique window to examine how brain states affect sensory processing by offering a ‘middle-tier’ alternative - a state where subjects are awake and responsive but already show behavioral deficits (Krause et al, 2017; Lim and Dinges, 2010).…”

Reduced neural feedback signaling despite robust neuron and gamma auditory responses during human sleep

“…On the other hand, other lines of evidence suggest robust responses during sleep, since discriminative processing persists for behaviorally relevant or semantic incongruent stimuli [7][8][9][10][11][12][13][14][15] as well as for contextual cues in targeted memory reactivation 16,17 . In addition, recent animal studies reporting comparable responses in the primary auditory cortex (A1) to stimuli across sleep and wakefulness have challenged the long-held assumption that natural sleep limits an effective relay to sensory cortex ('thalamic gating') as is the case for deep anesthesia [18][19][20][21][22][23][24][25] . Whether this is also the case in consolidated human sleep remains unknown, since it is possible that robust auditory responses reflect a sentinel-like process that is unique to fragmented sleep in prey animals.…”

Sleep-like changes in neural processing emerge during sleep deprivation in early auditory cortex

“…The copyright holder for this preprint this version posted March 7, 2022. ; https://doi.org/10.1101/2022.03.06.483154 doi: bioRxiv preprint sleep (Bergman et al, 2022;Wang, 2011, 2013;Krom et al, 2020;Nir et al, 2013a;Nourski et al, 2018;Raz et al, 2014;Sela et al, 2020). In this context, SD affords an additional unique window to examine how brain states affect sensory processing by offering a 'middle-tier' alternative -a state where subjects are awake and responsive but already show behavioral deficits (Krause et al, 2017;Lim and Dinges, 2010).…”