Neurobiology and Neuroprotective Benefits of Sleep

Logan Schneider, MD Sleep Neurology p. 848-870 August 2020, Vol.26, No.4 doi: 10.1212/CON.0000000000000878
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PURPOSE OF REVIEW This article outlines the neurocircuitry underlying sleep-wake and circadian physiology with a focus on the fundamental roles that sleep and circadian health play in optimal neurologic function.

RECENT FINDINGS The foundation of sleep and wake promotion is laid primarily by the “fast-acting” neurotransmitters: γ-aminobutyric acid (GABA) for sleep and glutamate for wake. External to these primary systems are a host of modulatory systems that are characterized by two flip-flop switches of mutually inhibitory neurotransmitter systems that facilitate transitions between wake and sleep as well as non–rapid eye movement (non-REM) and REM sleep. Additional mechanisms are in place to help coordinate the sleep-wake states with environmental, metabolic, and behavioral demands. The complexity of the evolutionarily preserved sleep-wake and circadian systems, the proportion of the day dedicated to the natural sleeping period, as well as the neurocognitive dysfunction and neurodegeneration caused by deficient sleep highlight the importance of defining, assessing, and optimizing the sleep health of our patients and ourselves.

SUMMARY Exciting discoveries continue to elucidate the underlying mechanisms of sleep and wake state coordination, reinforcing fundamental healthy practices and paving the way for new interventions that preserve and promote optimal neurologic health.

Address correspondence to Dr Logan Schneider, Stanford/VA Alzheimer’s Research Center, 3801 Miranda Ave, Building 4, C-141, Mail Code 116F-PAD, Palo Alto, CA 94304,

RELATIONSHIP DISCLOSURE: Dr Schneider has served as an editorial board member for Practical Neurology and Sleep and Breathing and has received personal compensation for serving on the speakers’ bureau for Harmony Biosciences, LLC, and Jazz Pharmaceuticals, Inc, and as a sleep health consultant for Alphabet Inc. Dr Schneider has received research/grant support as a VISN 21 research fellow from the US Department of Veteran Affairs Mental Illness Research, Education and Clinical Centers.


© 2020 American Academy of Neurology.