PT  - JOURNAL ARTICLE
AU  - Lottem Bergman
AU  - Aaron J Krom
AU  - Yaniv Sela
AU  - Amit Marmelshtein
AU  - Hanna Hayat
AU  - Noa Regev
AU  - Yuval Nir
TI  - Anesthetic Drug Concentration Rather Than Abrupt Behavioral Unresponsiveness Linearly Degrades Responses in the Rat Primary Auditory Cortex
AID  - 10.1101/2020.10.28.359323
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.28.359323
4099  - http://biorxiv.org/content/early/2020/10/29/2020.10.28.359323.short
4100  - http://biorxiv.org/content/early/2020/10/29/2020.10.28.359323.full
AB  - 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 StatementThe authors have declared no competing interest.