Anesthetic Drug Concentration Rather Than Abrupt Behavioral Unresponsiveness Linearly Degrades Responses in the Rat Primary Auditory Cortex

• Published in: bioRxiv
• Main Authors: Bergman, Lottem, Krom, Aaron J, Sela, Yaniv, Marmelshtein, Amit, Hayat, Hanna, Regev, Noa, Nir, Yuval
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 29.10.2020
• Subjects: Anesthesia; Cortex (auditory); Cortex (somatosensory); Firing pattern; Hearing; Information processing; Intravenous administration; Propofol; Righting reflex; Sensory integration; Sleep and wakefulness
• DOI: 10.1101/2020.10.28.359323

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 vs. behavioral unresponsiveness, since these are typically confounded. To address these questions, we employed slow gradual intravenous propofol anesthesia induction (from 100 to 900-1200 mcg/kg/min) together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording neuronal spiking activity in the primary auditory cortex (PAC) of eight male rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, post-onset neuronal silence duration, and late-locking to 40Hz clicktrains, gradually deteriorated by 6-60% in a dose-dependent manner with increasing anesthesia levels, without showing abrupt changes 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 recapitulate, within one experiment, a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (just-hypnotic vs. deep surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences. Competing Interest Statement The authors have declared no competing interest.