TY - JOUR
T1 - Interstitial ions
T2 - A key regulator of state-dependent neural activity?
AU - Rasmussen, Rune
AU - O'Donnell, John
AU - Ding, Fengfei
AU - Nedergaard, Maiken
N1 - Funding Information:
R.R. was supported by a Lundbeck Foundation PhD Scholarship (R230-2016-2326). J.O. was supported by the National Institute of Neurological Disorders and Stroke (U.S. National Institutes of Health: F32NS105365). M.N. was supported by The Novo Nordisk, Lundbeck Foundation, National Institute of Neurological Disorders and Stroke and the National Institute on Aging (U.S. National Institutes of Health: R01NS100366; RF1AG057575), and the U.S. Army Research Office (grant no. MURI W911NF1910280). The views and conclusions contained in this manuscript are solely those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the National Institutes of Health, Army Research Office, or the U.S. government. The U.S. government is authorized to reproduce and distribute reprints for government purposes notwithstanding any copyright notation herein.
Funding Information:
R.R. was supported by a Lundbeck Foundation PhD Scholarship ( R230-2016-2326 ). J.O. was supported by the National Institute of Neurological Disorders and Stroke (U.S. National Institutes of Health: F32NS105365 ). M.N. was supported by The Novo Nordisk , Lundbeck Foundation , National Institute of Neurological Disorders and Stroke and the National Institute on Aging (U.S. National Institutes of Health: R01NS100366 ; RF1AG057575 ), and the U.S. Army Research Office (grant no. MURI W911NF1910280 ). The views and conclusions contained in this manuscript are solely those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the National Institutes of Health, Army Research Office, or the U.S. government. The U.S. government is authorized to reproduce and distribute reprints for government purposes notwithstanding any copyright notation herein.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Calcium
KW - Huntington's disease
KW - Magnesium
KW - Neuromodulators
KW - Potassium
UR - http://www.scopus.com/inward/record.url?scp=85085600838&partnerID=8YFLogxK
U2 - 10.1016/j.pneurobio.2020.101802
DO - 10.1016/j.pneurobio.2020.101802
M3 - Review article
C2 - 32413398
AN - SCOPUS:85085600838
SN - 0301-0082
VL - 193
JO - Progress in Neurobiology
JF - Progress in Neurobiology
M1 - 101802
ER -