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

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.

[1]  D. McTigue,et al.  Syncytial Isopotentiality: An Electrical Feature of Spinal Cord Astrocyte Networks , 2018, Neuroglia.

[2]  D. McTigue,et al.  Dissipation of transmembrane potassium gradient is the main cause of cerebral ischemia-induced depolarization in astrocytes and neurons , 2018, Experimental Neurology.

[3]  Yong Ho Kim,et al.  Astrocytic Neuroligins Control Astrocyte Morphogenesis and Synaptogenesis , 2017, Nature.

[4]  L. Iyer,et al.  Molecular and Functional Properties of Regional Astrocytes in the Adult Brain , 2017, The Journal of Neuroscience.

[5]  B. Barres,et al.  Reactive Astrocytes: Production, Function, and Therapeutic Potential. , 2017, Immunity.

[6]  D. Rowitch,et al.  Functional diversity of astrocytes in neural circuit regulation , 2016, Nature Reviews Neuroscience.

[7]  H. Kettenmann,et al.  Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus , 2016, Cerebral cortex.

[8]  Qi Wang,et al.  Electrophysiological behavior of neonatal astrocytes in hippocampal stratum radiatum , 2016, Molecular Brain.

[9]  P. J. Sjöström,et al.  Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling , 2016, Science.

[10]  D. Terman,et al.  Gap junction coupling confers isopotentiality on astrocyte syncytium , 2016, Glia.

[11]  Dimitri Perrin,et al.  Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging , 2015, Nature Protocols.

[12]  D. Cope,et al.  Characterization of Panglial Gap Junction Networks in the Thalamus, Neocortex, and Hippocampus Reveals a Unique Population of Glial Cells. , 2015, Cerebral cortex.

[13]  James G. King,et al.  Reconstruction and Simulation of Neocortical Microcircuitry , 2015, Cell.

[14]  G. Perea,et al.  Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways , 2015, Science.

[15]  A. Nimmerjahn,et al.  Large-scale recording of astrocyte activity , 2015, Current Opinion in Neurobiology.

[16]  Min Zhou,et al.  Freshly dissociated mature hippocampal astrocytes exhibit passive membrane conductance and low membrane resistance similarly to syncytial coupled astrocytes. , 2015, Journal of neurophysiology.

[17]  Dimitri Perrin,et al.  Whole-Body Imaging with Single-Cell Resolution by Tissue Decolorization , 2014, Cell.

[18]  M. Freeman,et al.  Neuron-Glia Interactions through the Heartless FGF Receptor Signaling Pathway Mediate Morphogenesis of Drosophila Astrocytes , 2014, Neuron.

[19]  E. Susaki,et al.  Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis , 2014, Cell.

[20]  Nicolas Liaudet,et al.  Astrocyte Ca2+ signalling: an unexpected complexity , 2014, Nature Reviews Neuroscience.

[21]  Min Zhou,et al.  Spatial organization of NG2 glial cells and astrocytes in rat hippocampal CA1 region , 2014, Hippocampus.

[22]  Min Zhou,et al.  Dual patch voltage clamp study of low membrane resistance astrocytes in situ , 2014, Molecular Brain.

[23]  K. Kawakami,et al.  Development of Cerebellar Neurons and Glias Revealed by in Utero Electroporation: Golgi-Like Labeling of Cerebellar Neurons and Glias , 2013, PloS one.

[24]  T. Jakobs,et al.  Structural Remodeling of Astrocytes in the Injured CNS , 2012, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[25]  Masanori Murayama,et al.  Inhibitory Regulation of Dendritic Activity in vivo , 2012, Front. Neural Circuits.

[26]  L. Roux,et al.  Plasticity of astroglial networks in olfactory glomeruli , 2011, Proceedings of the National Academy of Sciences.

[27]  J. Rothstein,et al.  Molecular comparison of GLT1+ and ALDH1L1+ astrocytes in vivo in astroglial reporter mice , 2011, Glia.

[28]  B. Barres,et al.  Astrocyte heterogeneity: an underappreciated topic in neurobiology , 2010, Current Opinion in Neurobiology.

[29]  H. Kimelberg,et al.  Functions of Mature Mammalian Astrocytes: A Current View , 2010, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[30]  L. Roux,et al.  Over Astroglial Networks: a Step Further in Neuroglial and Gliovascular Interactions , 2022 .

[31]  Min Zhou,et al.  Electrical coupling of astrocytes in rat hippocampal slices under physiological and simulated ischemic conditions , 2009, Glia.

[32]  Michael Wong,et al.  Impaired astrocytic gap junction coupling and potassium buffering in a mouse model of tuberous sclerosis complex , 2009, Neurobiology of Disease.

[33]  Nathalie Rouach,et al.  Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission , 2008, Science.

[34]  H. Hirase,et al.  Cortical Layer 1 and Layer 2/3 Astrocytes Exhibit Distinct Calcium Dynamics In Vivo , 2008, PloS one.

[35]  C. Giaume,et al.  Gap Junction-Mediated Astrocytic Networks in the Mouse Barrel Cortex , 2008, The Journal of Neuroscience.

[36]  Takahiro Takano,et al.  Loss of Astrocytic Domain Organization in the Epileptic Brain , 2008, The Journal of Neuroscience.

[37]  C. Petersen The Functional Organization of the Barrel Cortex , 2007, Neuron.

[38]  Milos Pekny,et al.  Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury , 2006, Proceedings of the National Academy of Sciences.

[39]  U. Heinemann,et al.  The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus , 2006, The Journal of Neuroscience.

[40]  Nathalie Rouach,et al.  Shapes of astrocyte networks in the juvenile brain. , 2006, Neuron glia biology.

[41]  Oliver Peters,et al.  Activity-dependent ATP-waves in the mouse neocortex are independent from astrocytic calcium waves. , 2006, Cerebral cortex.

[42]  Mark Ellisman,et al.  Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development , 2004, International Journal of Developmental Neuroscience.

[43]  Mark Ellisman,et al.  Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains , 2002, The Journal of Neuroscience.

[44]  J. Nagy,et al.  Connexin30 in rodent, cat and human brain: selective expression in gray matter astrocytes, co-localization with connexin43 at gap junctions and late developmental appearance , 1999, Neuroscience.

[45]  J Wenzel,et al.  Functional Specialization and Topographic Segregation of Hippocampal Astrocytes , 1998, The Journal of Neuroscience.

[46]  B W Connors,et al.  Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I , 1998, The Journal of comparative neurology.

[47]  J. Parnavelas,et al.  Gap junctions in the adult cerebral cortex: Regional differences in their distribution and cellular expression of connexins , 1996, The Journal of comparative neurology.

[48]  S. Hestrin,et al.  Morphology and Physiology of Cortical Neurons in Layer I , 1996, The Journal of Neuroscience.

[49]  I. K. Wood,et al.  Neuroscience: Exploring the brain , 1996 .

[50]  T. Möller,et al.  Electrical coupling among Bergmann glial cells and its modulation by glutamate receptor activation , 1996 .

[51]  E. Hertzberg,et al.  Elevated connexin43 immunoreactivity at sites of amyloid plaques in alzheimer's disease , 1996, Brain Research.

[52]  J. Winer,et al.  Morphology and spatial distribution of GABAergic neurons in cat primary auditory cortex (AI) , 1994, The Journal of comparative neurology.

[53]  E. Hertzberg,et al.  On the organization of astrocytic gap junctions in rat brain as suggested by LM and EM immunohistochemistry of connexin43 expression , 1990, The Journal of comparative neurology.

[54]  S. Waxman,et al.  Specificity of cell-cell coupling in rat optic nerve astrocytes in vitro. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[55]  E. Hertzberg,et al.  LM and EM immunolocalization of the gap junctional protein connexin 43 in rat brain , 1990, Brain Research.

[56]  G. Palm,et al.  Density of neurons and synapses in the cerebral cortex of the mouse , 1989, The Journal of comparative neurology.

[57]  S. Goldring,et al.  Ionic determinants of membrane potential of cells presumed to be glia in cerebral cortex of cat. , 1973, Journal of neurophysiology.

[58]  S. W. Kuffler,et al.  Physiological properties of glial cells in the central nervous system of amphibia. , 1966, Journal of neurophysiology.

[59]  M. Nedergaard,et al.  Physiology of Astroglia. , 2018, Physiological reviews.

[60]  Omer Ali Bayraktar,et al.  Astrocyte development and heterogeneity. , 2014, Cold Spring Harbor perspectives in biology.

[61]  H. Kettenmann,et al.  Astrocyte function is modified by Alzheimer's disease-like pathology in aged mice. , 2009, Journal of Alzheimer's disease : JAD.

[62]  S. Palay,et al.  The form of velate astrocytes in the cerebellar cortex of monkey and rat: High voltage electron microscopy of rapid Golgi preparations , 2004, Zeitschrift für Anatomie und Entwicklungsgeschichte.

[63]  T. Möller,et al.  Electrical coupling among Bergmann glial cells and its modulation by glutamate receptor activation. , 1996, Glia.

[64]  B. Ransom,et al.  Electrical coupling, without dye coupling, between mammalian astrocytes and oligodendrocytes in cell culture , 1990, Glia.