A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats

Abstract

Anesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of brain states, and consequently have differential effects on a multitude of neurophysiological factors, these outcomes vary based on dosages, the animal species used, and the pharmacological mechanisms specific to each anesthetic agent. Thus, our aim was to conduct a controlled comparison of spontaneous electrophysiological dynamics at a surgical plane of anesthesia under six common research anesthetics using a ubiquitous animal model, the Sprague-Dawley rat. From this direct comparison, we also evaluated which anesthetic agents may serve as pharmacological proxies for the electrophysiological features and dynamics of unconscious states such as sleep and coma. We found that at a surgical plane, pentobarbital, isoflurane and propofol all produced a continuous pattern of burst-suppression activity, which is a neurophysiological state characteristically observed during coma. In contrast, ketamine-xylazine produced synchronized, slow-oscillatory activity, similar to that observed during slow-wave sleep. Notably, both urethane and chloral hydrate produced the spontaneous, cyclical alternations between forebrain activation (REM-like) and deactivation (non-REM-like) that are similar to those observed during natural sleep. Thus, choice of anesthesia, in conjunction with continuous brain state monitoring, are critical considerations in order to avoid brain-state confounds when conducting neurophysiological experiments.

Anesthesia-related brain microstructure modulations detected by diffusion MRI

“…For example, EEG measurements in and mice and rats have shown that ketamine-xylazine produces synchronized, slowoscillatory activity similar to what can be observed during slow-wave sleep 3,51 . In contrast, in rats and humans isoflurane anesthesia produces patterns of burst-suppression mimicking a state of coma suggesting that ketamine-xylazine produces a physiological state closer to natural sleep when compared to isoflurane [51][52][53] . Interestingly, rodents under ketamine-xylazine anesthesia have been shown to have greatly increased CSF transportation compared to isoflurane anesthetized animals 54 .…”

“…However, anesthesia is not equivalent to natural sleep 50 and comparisons of these states are therefore inevitably flawed. Even though, different anesthetic agents can resemble the physiological state of sleep more closely than others 51 . For example, EEG measurements in and mice and rats have shown that ketamine-xylazine produces synchronized, slow-oscillatory activity similar to what can be observed during slow-wave sleep 3,51 .…”

“…Even though, different anesthetic agents can resemble the physiological state of sleep more closely than others 51 . For example, EEG measurements in and mice and rats have shown that ketamine-xylazine produces synchronized, slowoscillatory activity similar to what can be observed during slow-wave sleep 3,51 . In contrast, in rats and humans isoflurane anesthesia produces patterns of burst-suppression mimicking a state of coma suggesting that ketamine-xylazine produces a physiological state closer to natural sleep when compared to isoflurane [51][52][53] .…”

Functional Brain Networks in Preschool Children With Autism Spectrum Disorders

“…This study still has some limitations and due to the poor completion of natural sleep MRI in younger children, chloral hydrate sedation was chosen to assist in the completion of MRI. A recent study on brain activity in rats pointed out that brain activity in rats sedated with chloral hydrate has a rhythm similar to natural sleep, but of different duration ( 29 ). Therefore, our results on FC in the preschool children are not a true rs-MRI and more preparation will be needed to achieve a true resting state MRI, such as more sleep deprivation, late night examination time, more attempts, etc.…”

Functional states shape the spatiotemporal representation of local and cortex-wide neural activity in mouse sensory cortex

“…Although their main features are similar to those of slow-wave sleep (SWS) waves ( 3 , 23 ), slow waves under anesthesia occur more rhythmically and synchronously across the cortex, show longer periods of inactivity between waves than during SWS ( 36 , 37 ), and represent a biologically and potentially clinically significant neural phenomenon ( 33 ). Persistent activity (PA) and slow wave activity (SWA) are both used as underlying conditions in neurophysiological studies that are performed under anesthesia or sedation ( 42 ), and variations of these states can similarly occur in awake animals. The current underlying cortical state might represent an important variable both for anesthetized preparations and for experiments performed in awake animals ( 17 ).…”