The last 20 years have seen a substantial advancement in the understanding of the molecular targets of general anaesthetics however the neural mechanisms involved in causing loss of consciousness remain poorly understood. Thalamocortical oscillations are present in natural sleep and are induced by many general anaesthetics suggesting that modulation of this reciprocal system may be involved in the regulation of consciousness.
Dynamic changes of thalamocortical oscillations in natural sleep and anaesthesia were investigated in rats chronically implanted with skull screw and depth electrodes in the cortex and thalamus. The hypothesis that discrete areas within the thalamus are responsible for regulation of arousal was tested. The anaesthetics propofol and dexmedetomidine but not midazolam produced switches in delta frequency at loss of righting reflex (LORR). This switch in frequency mirrored that seen within non-rapid eye movement sleep (NREM), whereas the onset of NREM was characterized by a switch from theta to delta in the EEG.
Depth recordings during NREM indicated that the switch into a NREM state occurred in the central medial thalamus (CMT) significantly before the cingulate, barrel cortex and ventrobasal nucleus (VB), and that the CMT switch corresponded to the switch seen in the global EEG. Dexmedetomidine hypnosis showed a delta frequency shift that occurred simultaneously within the thalamus and cortex, and furthermore that the thalamus exhibited phase advancement over the cortex at the point of LORR.
In conclusion, globalised changes within the thalamocortical system occur for propofol and dexmedetomidine LORR in the rat. This change represents a transition within drug free NREM and may implicate a common pathway responsible for a decrease in arousal. Furthermore, the phase advancement of the intralaminar thalamus over the cortex at LORR suggests a crucial role for this part of the thalamocortical system for regulating consciousness.