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      Epileptiform Neuronal Discharges Impair Astrocyte Syncytial Isopotentiality in Acute Hippocampal Slices


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          Astrocyte syncytial isopotentiality is a physiological mechanism resulting from a strong electrical coupling among astrocytes. We have previously shown that syncytial isopotentiality exists as a system-wide feature that coordinates astrocytes into a system for high efficient regulation of brain homeostasis. Neuronal activity is known to regulate gap junction coupling through alteration of extracellular ions and neurotransmitters. However, the extent to which epileptic neuronal activity impairs the syncytial isopotentiality is unknown. Here, the neuronal epileptiform bursts were induced in acute hippocampal slices by removal of Mg 2+ (Mg 2+ free) from bath solution and inhibition of γ-aminobutyric acid A (GABA A) receptors by 100 µM picrotoxin (PTX). The change in syncytial coupling was monitored by using a K + free-Na +-containing electrode solution ([Na +] p) in the electrophysiological recording where the substitution of intracellular K + by Na + ions dissipates the physiological membrane potential (V M) to ~0 mV in the recorded astrocyte. However, in a syncytial coupled astrocyte, the [Na +] p induced V M loss can be compensated by the coupled astrocytes to a quasi-physiological membrane potential of ~73 mV. After short-term exposure to this experimental epileptic condition, a significant closure of syncytial coupling was indicated by a shift of the quasi-physiological membrane potential to −60 mV, corresponding to a 90% reduction of syncytial coupling strength. Consequently, the closure of syncytial coupling significantly decreased the ability of the syncytium for spatial redistribution of K + ions. Altogether, our results show that epileptiform neuronal discharges weaken the strength of syncytial coupling and that in turn impairs the capacity of a syncytium for spatial redistribution of K + ions.

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          Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo.

          Glial cells have been identified as key signaling components in the brain; however, methods to investigate their structure and function in vivo have been lacking. Here, we describe a new, highly selective approach for labeling astrocytes in intact rodent neocortex that allows in vivo imaging using two-photon microscopy. The red fluorescent dye sulforhodamine 101 (SR101) was specifically taken up by protoplasmic astrocytes after brief exposure to the brain surface. Specificity was confirmed by immunohistochemistry. In addition, SR101 labeled enhanced green fluorescent protein (EGFP)-expressing astrocytes but not microglial cells in transgenic mice. We used SR101 labeling to quantify morphological characteristics of astrocytes and to visualize their close association with the cortical microvasculature. Furthermore, by combining this method with calcium indicator loading of cell populations, we demonstrated distinct calcium dynamics in astroglial and neuronal networks. We expect SR101 staining to become a principal tool for investigating astroglia in vivo.
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            Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex.

            Astrocytes have long been thought to act as a support network for neurons, with little role in information representation or processing. We used two-photon imaging of calcium signals in the ferret visual cortex in vivo to discover that astrocytes, like neurons, respond to visual stimuli, with distinct spatial receptive fields and sharp tuning to visual stimulus features including orientation and spatial frequency. The stimulus-feature preferences of astrocytes were exquisitely mapped across the cortical surface, in close register with neuronal maps. The spatially restricted stimulus-specific component of the intrinsic hemodynamic mapping signal was highly sensitive to astrocyte activation, indicating that astrocytes have a key role in coupling neuronal organization to mapping signals critical for noninvasive brain imaging. Furthermore, blocking astrocyte glutamate transporters influenced the magnitude and duration of adjacent visually driven neuronal responses.
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              Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia.


                Author and article information

                Brain Sci
                Brain Sci
                Brain Sciences
                02 April 2020
                April 2020
                : 10
                : 4
                : 208
                [1 ]Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA; Qi.Wang@ 123456osumc.edu (Q.W.); wwang@ 123456hust.edu.cn (W.W.); Aten.19@ 123456osu.edu (S.A.); kiyoshi.1@ 123456osu.edu (C.M.K.)
                [2 ]Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
                Author notes
                [* ]Correspondence: du.377@ 123456osu.edu (Y.D.); zhou.787@ 123456osu.edu (M.Z.); Tel.: +1-614-366-9409 (Y.D.); +1-614-366-9406 (M.Z.)
                Author information
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 29 February 2020
                : 31 March 2020

                astrocytes,gap junction,astrocyte syncytial isopotentiality,epilepsy,potassium homeostasis


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