Spectral Properties of Brain Activity Under Two Anesthetics and Their Potential for Inducing Natural Sleep in Birds

Abstract

Both mammals and birds exhibit two sleep states, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Studying certain aspects of sleep-related electrophysiology in freely behaving animals can present numerous methodological constraints, particularly when even fine body movements interfere with electrophysiological signals. Interestingly, under light general anesthesia, mammals and birds also exhibit slow waves similar to those observed during natural SWS. For these reasons, slow waves occurring under general anesthesia are commonly used in the investigation of sleep-related neurophysiology. However, how spectral properties of slow waves induced by anesthesia correspond to those occurring during natural SWS in birds has yet to be investigated systematically. In this study, we systematically analyzed spectral properties of electroencephalographic (EEG) patterns of pigeons (Columba livia) occurring under two commonly used anesthetics, isoflurane and urethane. These data were compared with EEG patterns during natural sleep. Slow waves occurring during spontaneous SWS, and those induced with isoflurane and urethane all showed greatest absolute power in the slowest frequencies (<3 Hz). Isoflurane and urethane-induced slow waves had near-identical power spectra, and both had higher mean power than that observed during SWS for all frequencies examined (0–25 Hz). Interestingly, burst suppression EEG activity observed under deeper planes of isoflurane anesthesia could occur bihemispherically or unihemispherically. Electrophysiological patterns while under isoflurane and urethane share phenomenological and spectral similarities to those occurring during SWS, notably the generation of high amplitude, slow waves, and peak low-frequency power. These results build upon other studies which suggest that some anesthetics exert their effects by acting on natural sleep pathways. As such, anesthesia-induced slow waves appear to provide an acceptable model for researchers interested in investigating sleep-related slow waves utilizing electrophysiological methods not suitable for use in freely behaving birds.

Neurophysiology of Avian Sleep: Comparing Natural Sleep and Isoflurane Anesthesia

“…Nonetheless, the power spatial distribution in the slow-wave frequency band (i.e., 1.5–5 Hz) under low (1.5%) isoflurane anesthesia is more comparable to NREM sleep than to wake and REM sleep, suggesting that slow-waves during isoflurane anesthesia are similar, though stronger, than slow-waves under NREM sleep. This finding is in agreement with a recent EEG study in pigeons (Tisdale et al, 2018). Interestingly, cats anesthetized with ketamine-xylazine exhibit lower power in the low frequencies (0.1–4 Hz and 8–14 Hz) when compared to NREM sleep (Chauvette et al, 2011).…”

“…Moreover, anesthesia (often isoflurane) is used in other fields, such as the neuroscience of birdsong (e.g., Beckers and Gahr, 2012; Menardy et al, 2014). Although there is EEG evidence for parallels between NREM sleep and isoflurane anesthesia in birds (Tisdale et al, 2018), a comparison of the underlying intra-cortical brain activity has been lacking. Using intra-cortical high-density electrode array recordings from the same naturally sleeping and isoflurane anesthetized pigeons, we characterized and compared the spatio-temporal properties of slow-waves in the avian hyperpallium occurring during both states.…”

“…Consequently, brain activity during the lowest level of isoflurane (i.e., 1.5%) possible to measure from in this study most closely resembles NREM sleep. The low amplitude activity visible during some episodes of suppression states are of unknown origin but might be caused by local processes, artifacts on the recordings sites or volume conduction from multiple, dispersed sources further away in the same hemisphere or from the left hemisphere, as slow-waves (i.e., burst state) can occur asynchronously between hemispheres (Rattenborg and Amlaner, 2010; Tisdale et al, 2018). Second, the LFP negative peak amplitude was significantly larger (i.e., more negative) during anesthesia when compared to NREM sleep.…”

“…To our knowledge, this is the first direct comparison of intra-cortical brain activity during wake, NREM sleep, and REM sleep, and different levels of isoflurane anesthesia in birds. We opted for isoflurane in this study as this is a common anesthetic used in lab studies examining the neurophysiology of avian sleep (e.g., Beckers et al, 2014, Tisdale et al, 2018) and the neurological correlates of bird song (e.g., Beckers and Gahr, 2012; Menardy et al, 2014). Nonetheless, future research should consider examining other anesthetics (Zhang et al, 2015).…”

“…Few studies have examined sleep-related brain activity in birds under anesthesia. The burst suppression pattern has been observed in chickens anesthetized with pentobarbital (Ookawa and Gotoh, 1965; Kadono et al, 1967; Ookawa and Takenaka, 1967; Ookawa, 1972), and zebra finches, chickens, and pigeons anesthetized with isoflurane (Beckers et al, 2014; Mcilhone et al, 2014; Tisdale et al, 2018). However, as no direct comparison of LFP slow-waves occurring during anesthesia and NREM sleep has been conducted across the hyperpallial pseudo-layers, the question remains to what extent slow-waves under anesthesia are comparable to NREM sleep slow-waves.…”