Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders

Abstract

Brain activation during wakefulness is sustained by multiple arousal systems. Dysfunction of one or more arousal systems is a feature of neurological disorders associated with hypersomnolence and/or sleep-wake cycle disturbance. Narcolepsy, Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury appear to involve hypocretin (HCT) and possibly histamine insufficiency as a mechanism related to excessive daytime sleepiness. Loss of cholinergic neurons in AD and of dopamine neurons in PD contributes to sleepwake disturbance. GABAergic neurons in the preoptic hypothalamus and rostral medulla promote sleep through inhibition of arousal systems. Pathology of preoptic sleep regulatory circuits is correlated with sleep disturbance in AD. An unidentified endogenous somnogen that potentiates the actions of gamma-aminobutyric acid (GABA) is present in the cerebrospinal fluid (CSF) of patients with primary hypersomnia.Descending pathways from the dorsal lateral pons to the ventral medulla and spinal cord are responsible for the inhibition of spinal motoneurons during rapid eye movement (REM) sleep and are implicated in human REM sleep behavior disorder.

Insights into the Frequency and Distinguishing Features of Sleep Disorders in Pediatric Palliative Care Incorporating a Systematic Sleep Protocol

“…Hypersomnia seems to be characterized by a rapid, hardly quantifiable change between wakefulness and sleep during the day. Some evidence suggests that the establishment and maintenance of an adequate arousal level may be impaired, particularly in the case of neurological diseases accompanied by functional or structural changes of the brain and central nervous system [ 37 , 38 ]. Since the majority of the participating patients had neurological diseases, it is plausible that these processes might have been disturbed.…”

Steps Towards Developing Effective Treatments for Neuropsychiatric Disturbances in Alzheimer’s Disease: Insights From Preclinical Models, Clinical Data, and Future Directions

“…The SCN neurons project to different areas of the hypothalamus in a complex manner and these projections are responsible for the circuit activity of neurotransmitters and neuropeptides that regulate the sleep/wake cycle. These include melatonin, serotonin, NE, acetylcholine, glutamate, GABA, dopamine, orexin, neurotensin, vasopressin, and vasoactive intestinal peptide (VIP; Lim and Szymusiak, 2015;Van Erum et al, 2018). A detailed description of the circuits is beyond the scope of this review.…”

Ascending Reticular Activating System of the Brain

“…Thus, the cerebral ascending reticular activating system (ARAS) particularly responsible for waking maintenance was discovered. Initially, it was considered to be diffused; however, modern neuromorphology has distinguished about ten separate clusters of nerve cell bodies releasing various chemical mediators, the so-called "waking centers" that are located "inside" the ARAS at all the levels of the cerebral axis [2,[4][5][6] (Figure 1a). After the studies by Moruzzi and Magoun, it became clear that the normal functioning of the thalamocortical system of the brain, which provides the entire range of human conscious activity during wakefulness, is possible only if a strong tonic activating inflow from the definite subcortical structures is available [7] .…”

“…Thus, the cerebral ascending reticular activating system (ARAS) particularly responsible for waking maintenance was discovered. Initially, it was considered to be diffused; however, modern neuromorphology has distinguished about ten separate clusters of nerve cell bodies releasing various chemical mediators, the so-called "waking centers" that are located "inside" the ARAS at all the levels of the cerebral axis [2,[4][5][6] (Figure 1a).…”

“…The latter is critical for position maintenance and voluntary movement performance. A general description of the ascending activating system as provided at the end of the first decade of the 21st century is the topic of several recent important reviews [2,[4][5][6] .…”