The Effect of Slow Induction of Propofol on Responses to 40Hz Click-trains in the Rat Auditory Cortex

Background: The causes of anesthetic-induced loss of consciousness (LOC) and how responses to sensory stimuli differ across wakefulness and anesthesia are not well understood. Most previous research compared wakefulness with deep anesthesia, where neuronal activity changes along with temperature, blood perfusion, and other confounding factors. Here we employed gradual anesthesia induction together with auditory stimulation to try to isolate changes in sensory responses that occur around LOC.

Methods and Results: Adult male Long-Evans rats (n=6) were implanted with microwire arrays in right A1. After recovery and habituation, auditory stimuli were presented (free-field) in a sound-proof environment. Anesthesia was slowly and gradually induced by administering propofol (from 100 to 900-1200 mcg/kg/min) through a chronic intravenous jugular vein catheter controlled with a computerized infusion pump. Behavioral (un)responsiveness was assessed every 12 minutes by testing of righting reflex, corneal and whisker reflexes, and paw withdrawal. LFPs and single/multi-unit activities (n=96 microwires) were recorded continuously along with epidural EEG, EMG and video and compared between wakefulness and anesthesia. Preliminary results suggest that LFP responses to 500ms-long 40Hz click-trains show a strong onset response followed by a steady-state component at the stimulation frequency that was strongly modulated by anesthesia. Firing of isolated neuronal units shows a gradual increase in response latency that follows gradual increases in anesthetic concentration. In contrast, an abrupt breakdown of trial-by-trial response consistency is observed shortly after loss of righting reflex (LORR). We are now expanding this research to other anesthetic agents, auditory stimuli, and cortical regions beyond A1.

Acknowledgements: Supported by ISF 51/11 (I-CORE cognitive sciences), ISF 1326/15, FP7 CIG, and Adelis Foundation (YN); ISF 762/16 and the ESA (AJK)