Journal
PROGRESS IN NEUROBIOLOGY
Volume 193, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2020.101802
Keywords
Potassium; Calcium; Magnesium; Astrocytes; Neuromodulators; Huntington's disease
Categories
Funding
- Lundbeck Foundation PhD Scholarship [R230-2016-2326]
- National Institute of Neurological Disorders and Stroke (U.S. National Institutes of Health) [F32NS105365]
- Novo Nordisk
- Lundbeck Foundation
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging (U.S. National Institutes of Health) [R01NS100366, RF1AG057575]
- U.S. Army Research Office [MURI W911NF1910280]
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Throughout the nervous system, ion gradients drive fundamental processes. Yet, the roles of interstitial ions in brain functioning is largely forgotten. Emerging literature is now revitalizing this area of neuroscience by showing that interstitial cations (K+, Ca2+ and Mg2+) are not static quantities but change dynamically across states such as sleep and locomotion. In turn, these state-dependent changes are capable of sculpting neuronal activity; for example, changing the local interstitial ion composition in the cortex is sufficient for modulating the prevalence of slow-frequency neuronal oscillations, or potentiating the gain of visually evoked responses. Disturbances in interstitial ionic homeostasis may also play a central role in the pathogenesis of central nervous system diseases. For example, impairments in K+ buffering occur in a number of neurodegenerative diseases, and abnormalities in neuronal activity in disease models disappear when interstitial K+ is normalized. Here we provide an overview of the roles of interstitial ions in physiology and pathology. We propose the brain uses interstitial ion signaling as a global mechanism to coordinate its complex activity patterns, and ion homeostasis failure contributes to central nervous system diseases affecting cognitive functions and behavior.
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