Monoamines: Dopamine, Norepinephrine, and Serotonin, Beyond Modulation, "Switches" That Alter the State of Target Networks.

How do monoamines influence the perceptual and behavioral aspects of brain function? A library of information regarding the genetic, molecular, cellular, and function of monoamines in the nervous system and other organs has accumulated. We briefly review monoamines' anatomy and physiology and discuss their effects on the target neurons and circuits. Monoaminergic cells in the brain stem receive inputs from sensory, limbic, and prefrontal areas and project extensively to the forebrain and hindbrain. We review selected studies on molecular, cellular, and electrophysiological effects of monoamines on the brain's target areas. The idea is that monoamines, by reversibly modulating the "primary" information processing circuits, regulate and switch the functions of brain networks and can reversibly alter the "brain states," such as consciousness, emotions, and movements. Monoamines, as the drivers of normal motor and sensory brain operations, including housekeeping, play essential roles in pathogenesis of neuropsychiatric diseases.

Role of the cerebellum in the phenotype of neurodegenerative diseases: Mitigate or exacerbate?

Degenerative diseases alter brain activity and functional connectivity. In this issue of the Neuroscience Letters, Yin and others (2021) [6] present data showing increased activity in lobules VIII and IX of the cerebellar vermis in Parkinson's patients with visuospatial disorders. The study refines the fMRI mapping of the cerebellum, but the functional interpretation of the findings remains complex. The architecture and connectivity of the cerebellum set it apart from the rest of the brain and should be considered when interpreting the functional connectivity data. In degenerative diseases, the cerebellum suffers from the same pathology as the cerebral cortex; hence, it is unlikely that changes in the cerebellum could ameliorate clinical symptoms in degenerative diseases. Clinical, surgical data indicate that the primary function of the cerebellum is motor, not cognition or affective. The cerebellar anatomy buttresses these observations. The cerebellum receives direct motor-related inputs but no direct information from the sensory system. Hence, it likely contributes to the behavioral components of emotions and cognition.

Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells.

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.