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Brainstem: Mech of Consciousness

Consciousness can be most simply described as an awake state of awareness although the specific definition and concept has been debated for ages by scientists and philosophers alike. Neural correlates of consciousness are the minimum neuronal mechanisms jointly sufficient for any one specific conscious experience. While higher level processing in the thalamus and cerebral cortex are necessary for conscious experiences in their entirety, the most basic requirement for consciousness is located in the brainstem.

The reticular formation is a network of brainstem nuclei without precisely defined boundaries ranging from the medulla to the midbrain. It includes two major neuronal pathways: the descending reticulospinal tracts and the ascending reticular activating system (ARAS). The ARAS has several critical functions with projections to thalamus and cerebral cortex that are necessary for consciousness, arousal, sleep-wake cycles, cardiovascular and respiratory control, pain regulation, coordination of somatic motor movements, and habituation. The ARAS system contains glutamatergic, cholinergic, serotonergic, dopaminergic, noradrenergic, and histaminergic projections to several nuclei including the locus coeruleus, raphe nuclei, pedunculopontine nucleus, parabrachial nuclei, and laterodorsal tegmental nucleus.

Abnormalities in the ascending reticular activating system are implicated in several disease processes such as hypersomnia, coma, schizophrenia, post-traumatic stress disorder, narcolepsy, and Parkinson’s disease. Unconsciousness in general anesthesia is achieved by targeting GABA-A and NMDA receptors throughout the brainstem, thalamus, striatum, and cortex as demonstrated in several in vivo and in vitro pharmacologic studies.

References

  1. Brown EN, Lydic R, Schiff ND. General Anesthesia, Sleep, and Coma. N Engl J Med. 2010 Dec 30; 363(27): 2638–2650. PubMed Link
  2. Iqbal F, Thompson AJ, Riaz S, et al. Anesthetics: from Modes of Action to Unconsciousness and Neurotoxicity. J Neurophysiol. 2019;122:760-787. PubMed Link
  3. Mangold S, Das JM. Neuroanatomy, Reticular Formation. In: StatPearls. Treasure Island (FL) StatPearls Publishing 2021. PubMed Link