Syncytial isopotentiality: A system‐wide electrical feature of astrocytic networks in the brain

Abstract

Syncytial isopotentiality, resulting from a strong electrical coupling, emerges as a physiological mechanism that coordinates individual astrocytes to function as a highly efficient system in brain homeostasis. However, whether syncytial isopotentiality occurs selectively to certain brain regions or is universal to astrocytic networks remains unknown. Here, we have explored the correlation of syncytial isopotentiality with different astrocyte subtypes in various brain regions. Using a nonphysiological K+‐free/Na+ electrode solution to depolarize a recorded astrocyte in situ, the existence of syncytial isopotentiality can be revealed: the recorded astrocyte's membrane potential remains at a quasi‐physiological level due to strong electrical coupling with neighboring astrocytes. Syncytial isopotentiality appears in Layer I of the motor, sensory, and visual cortical regions, where astrocytes are organized with comparable cell densities, interastrocytic distances, and the quantity of directly coupled neighbors. Second, though astrocytes vary in their cytoarchitecture in association with neuronal circuits from Layers I–VI, the established syncytial isopotentiality remains comparable among different layers in the visual cortex. Third, neurons and astrocytes are uniquely organized as barrels in Layer IV somatosensory cortex; interestingly, astrocytes both inside and outside of the barrels do electrically communicate with each other and also share syncytial isopotentiality. Fourth, syncytial isopotentiality appears in radial‐shaped Bergmann glia and velate astrocytes in the cerebellar cortex. Fifth, although fibrous astrocytes in white matter exhibit a distinct morphology, their network syncytial isopotentiality is comparable with protoplasmic astrocytes. Altogether, syncytial isopotentiality appears as a system‐wide electrical feature of astrocytic networks in the brain.

Epileptiform Neuronal Discharges Impair Astrocyte Syncytial Isopotentiality in Acute Hippocampal Slices

“…Indeed, a strong electrical coupling does confer an isopotentiality to astrocyte Brain Sci. 2020, 10, 208 2 of 15 network across the brain [13][14][15]. In a demonstrated case, we showed that only under the syncytial isopotentiality, a sustained driving force can be maintained for high efficient K + uptake.…”

“…This indeed occurs in the single freshly dissociated astrocyte ( Figure 4A, left) where rupture of an astrocyte by [Na + ] p resulted in a progressive V M depolarization to 0 mV ( Figure 4B, green trace). Note that immediately after membrane rupture, the initial V M (V M , I ) reflects the resting V M of the cell, whereas the V M at the steady-state level (V M,SS ) reflects the V M of Nernstian prediction [13,15]. The V M,SS is −1.8 ± 1.7 mV in freshly dissociated single astrocytes (n = 6 recordings from five mice) ( Figure 4C, green bar).…”

“…All of the experimental procedures were performed in accordance with a protocol approved by the Animal Care and Use Committees of The Ohio State University. The wild type C57BL/6J and BAC-ALDH1L1-eGFP transgenic mice of both sexes at postnatal days (P) 21-28 were used in the present study [15,24,25]…”

“…We have previously shown that each astrocyte is directly coupled to 7-9 of the nearest neighbors and this spatial arrangement is a prerequisite for syncytial isopotentiality to be achieved [13][14][15]. To answer if the Mg 2+ free-PTX condition alters the cellular structure and spatial organization of astrocytes, we took advantage of BAC-ALDH1L1-eGFP transgenic mice to visualize astrocytes by their eGFP expression [14,15,25]. In acutely prepared brain slices, a feasible time window to examine the impact of the Mg 2+ free-PTX conditions on astrocyte anatomy and function is around 2-6 hours.…”

Molecular mechanisms of K+ clearance and extracellular space shrinkage—Glia cells as the stars

“…Gap junctional coupling thus serves to achieve isopotentiality in glial networks. This coupling ensures that the membrane potential of the connected glia cells remains hyperpolarized, to some extent, even when an individual cell is faced with elevated [K + ] o (Futamachi & Pedley, ; Kiyoshi et al, ; Ma et al, ). This functional network organization, taken together with the K + ‐selective glial membrane conductance, led Orkand and colleagues to coin the term “spatial buffering” in the discussion of their now classical article from 1966 (Orkand et al, ).…”