How Müller glial cells in macaque fovea coat and isolate the synaptic terminals of cone photoreceptors

A cone synaptic terminal in macaque fovea releases quanta of glutamate from ∼20 active zones at a high rate in the dark. The transmitter reaches ∼500 receptor clusters on bipolar and horizontal cell processes by diffusion laterally along the terminal's 50 μm2 secretory face and ∼2 μm inward. To understand what shapes transmitter flow, we investigated from electron photomicrographs of serial sections the relationship between Müller glial processes and cone terminals. We find that each Müller cell has one substantial trunk that ascends in the outer plexiform layer below the space between the “footprints” of the terminals. We find exactly equal numbers of Müller cell trunks and foveal cone terminals, which may make the fovea particularly vulnerable to Müller cell dysfunction. The processes that emerge from the single trunk do not ensheathe a single terminal. Instead, each Müller cell partially coats two to three terminals; in turn, each terminal is completely coated by two to three Müller cells. Therefore, the Müller cells that coat one terminal also partially coat the surrounding (∼ six) terminals, creating a common environment for the cones supplying the center/surround receptive field of foveal midget bipolar and ganglion cells. Upon reaching the terminals, the trunk divides into processes that coat the terminals' sides but not their secretory faces. This glial framework minimizes glutamate transporter (EAAT1) beneath a terminal's secretory face but maximizes EAAT1 between adjacent terminals, thus permitting glutamate to diffuse locally along the secretory face and inward toward inner receptor clusters but reducing its effective spillover to neighboring terminals. J. Comp. Neurol. 453:100–111, 2002. © 2002 Wiley‐Liss, Inc.

[1]  R. W. Guillery,et al.  The organization of synaptic interconnections in the laminae of the dorsal lateral geniculate nucleus of the cat , 2004, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[2]  J. Špaček Relationships between synaptic junctions, puncta adhaerentia and the spine apparatus at neocortical axo-spinous synapses , 2004, Anatomy and Embryology.

[3]  N. Danbolt Glutamate uptake , 2001, Progress in Neurobiology.

[4]  H. Wässle,et al.  The Synaptic Architecture of AMPA Receptors at the Cone Pedicle of the Primate Retina , 2001, The Journal of Neuroscience.

[5]  S. DeVries,et al.  Bipolar Cells Use Kainate and AMPA Receptors to Filter Visual Information into Separate Channels , 2000, Neuron.

[6]  D. Pow,et al.  Are neuronal transporters relevant in retinal glutamate homeostasis? , 2000, Neurochemistry International.

[7]  M. Kamermans,et al.  Immunocytochemical localization of the glutamate transporter GLT‐1 in goldfish (Carassius auratus) retina , 2000, The Journal of comparative neurology.

[8]  P Sterling,et al.  Localization of mGluR6 to dendrites of ON bipolar cells in primate retina , 2000, The Journal of comparative neurology.

[9]  Heinz Wässle,et al.  The Cone Pedicle, a Complex Synapse in the Retina , 2000, Neuron.

[10]  G. Kinney,et al.  Glutamate Transporters Contribute to the Time Course of Synaptic Transmission in Cerebellar Granule Cells , 1999, The Journal of Neuroscience.

[11]  Leon Lagnado,et al.  The retina , 1999, Current Biology.

[12]  D. Kullmann,et al.  Hippocampal synapses: do they talk to their neighbours? , 1999, Trends in Neurosciences.

[13]  H. Wässle,et al.  Modulation of the intracellular calcium concentration in photoreceptor terminals by a presynaptic metabotropic glutamate receptor. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Harris,et al.  Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes , 1999, The Journal of Neuroscience.

[15]  Dwight E Bergles,et al.  Clearance of glutamate inside the synapse and beyond , 1999, Current Opinion in Neurobiology.

[16]  J. Gass,et al.  Müller cell cone, an overlooked part of the anatomy of the fovea centralis: hypotheses concerning its role in the pathogenesis of macular hole and foveomacualr retinoschisis. , 1999, Archives of ophthalmology.

[17]  N. Vardi,et al.  Differential expression of ionotropic glutamate receptor subunits in the outer retina , 1999, The Journal of comparative neurology.

[18]  C. Kozak,et al.  The mouse X-linked juvenile retinoschisis cDNA: expression in photoreceptors. , 1999, Gene.

[19]  E. A. Schwartz,et al.  Kainate receptors mediate synaptic transmission between cones and ‘Off’ bipolar cells in a mammalian retina , 1999, Nature.

[20]  G Buchsbaum,et al.  Transmitter concentration at a three-dimensional synapse. , 1998, Journal of neurophysiology.

[21]  K. P. Lehre,et al.  The Number of Glutamate Transporter Subtype Molecules at Glutamatergic Synapses: Chemical and Stereological Quantification in Young Adult Rat Brain , 1998, The Journal of Neuroscience.

[22]  M. Kavanaugh,et al.  Macroscopic and Microscopic Properties of a Cloned Glutamate Transporter/Chloride Channel , 1998, The Journal of Neuroscience.

[23]  F. Werblin,et al.  Voltage-dependent uptake is a major determinant of glutamate concentration at the cone synapse: an analytical study. , 1998, Journal of neurophysiology.

[24]  C. Jahr,et al.  Glial Contribution to Glutamate Uptake at Schaffer Collateral–Commissural Synapses in the Hippocampus , 1998, The Journal of Neuroscience.

[25]  C. Jahr,et al.  Anion Currents and Predicted Glutamate Flux through a Neuronal Glutamate Transporter , 1998, The Journal of Neuroscience.

[26]  D. Kullmann,et al.  Activation of AMPA, Kainate, and Metabotropic Receptors at Hippocampal Mossy Fiber Synapses Role of Glutamate Diffusion , 1998, Neuron.

[27]  M. Kavanaugh,et al.  Localization and function of five glutamate transporters cloned from the salamander retina , 1998, Vision Research.

[28]  Peter Sterling,et al.  Neurochemistry of the mammalian cone `synaptic complex' , 1998, Vision Research.

[29]  D. Kullmann,et al.  Extrasynaptic Glutamate Diffusion in the Hippocampus: Ultrastructural Constraints, Uptake, and Receptor Activation , 1998, The Journal of Neuroscience.

[30]  M. Kavanaugh,et al.  Excitatory Amino Acid Transporters of the Salamander Retina: Identification, Localization, and Function , 1998, The Journal of Neuroscience.

[31]  D. Kullmann,et al.  Extrasynaptic glutamate spillover in the hippocampus: evidence and implications , 1998, Trends in Neurosciences.

[32]  P. Somogyi,et al.  Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1α, mGluR2 and mGluR5, relative to neurotransmitter release sites , 1997, Journal of Chemical Neuroanatomy.

[33]  T. I. Chao,et al.  Comparative studies on mammalian Muller (retinal glial) cells , 1997, Journal of neurocytology.

[34]  Paul Antoine Salin,et al.  Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors , 1997, Nature.

[35]  K. P. Lehre,et al.  Localization of the glutamate transporter protein GLAST in rat retina , 1997, Brain Research.

[36]  H. Wässle,et al.  Differential expression of three glutamate transporter subtypes in the rat retina , 1996, Cell and Tissue Research.

[37]  Paul R. Martin,et al.  The Synaptic Complex of Cones in the Fovea and in the Periphery of the Macaque Monkey Retina , 1996, Vision Research.

[38]  C. Distler,et al.  Glia Cells of the Monkey Retina—II. Müller Cells , 1996, Vision Research.

[39]  E. Newman,et al.  The Müller cell: a functional element of the retina , 1996, Trends in Neurosciences.

[40]  E. A. Schwartz,et al.  Asynchronous transmitter release: control of exocytosis and endocytosis at the salamander rod synapse. , 1996, The Journal of physiology.

[41]  J. Clements Transmitter timecourse in the synaptic cleft: its role in central synaptic function , 1996, Trends in Neurosciences.

[42]  L. Trussell,et al.  Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[43]  D. Diloreto,et al.  Müller cell changes precede photoreceptor cell degeneration in the age-related retinal degeneration of the Fischer 344 rat , 1995, Brain Research.

[44]  H Lecar,et al.  Cone photoreceptors respond to their own glutamate release in the tiger salamander. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[45]  A. Reichenbach,et al.  Müller glial cells of the tree shrew retina , 1995, The Journal of comparative neurology.

[46]  T. Rauen,et al.  Coincidence of L‐glutamate/L‐aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: Evidence for coupling of GLAST and GS in transmitter clearance , 1995, Journal of neuroscience research.

[47]  M. Kavanaugh,et al.  Kinetics of a human glutamate transporter , 1995, Neuron.

[48]  Laura Ballerini,et al.  Glutamate uptake from the synaptic cleft does not shape the decay of the non-NMDA component of the synaptic current , 1993, Neuron.

[49]  Peter Sterling,et al.  Gap junctions between the pedicles of macaque foveal cones , 1992, Vision Research.

[50]  G. Fishman,et al.  Dominantly inherited cystoid macular edema. A histopathologic study. , 1992, Ophthalmology.

[51]  C. Distler,et al.  Müller cells in vascular and avascular retinae: A survey of seven mammals , 1992, The Journal of comparative neurology.

[52]  P. Mobbs,et al.  The spatial relationship between Mu¨ller cell processes and the photoreceptor output synapse , 1992, Brain Research.

[53]  Z. Dreher,et al.  Müller cells in adult rabbit retinae: Morphology, distribution and implications for function and development , 1990, The Journal of comparative neurology.

[54]  W. Krebs,et al.  Quantitative morphology of the central fovea in the primate retina. , 1989, The American journal of anatomy.

[55]  S. Schein Anatomy of macaque fovea and spatial densities of neurons in foveal representation , 1988, The Journal of comparative neurology.

[56]  Robert G. Smith Montage: a system for three-dimensional reconstruction by personal computer , 1987, Journal of Neuroscience Methods.

[57]  W. Krebs,et al.  Quantitative morphology of the primate peripheral retina (Macaca irus). , 1987, The American journal of anatomy.

[58]  S. Brownstein,et al.  Congenital hereditary (juvenile X-linked) retinoschisis. Histopathologic and ultrastructural findings in three eyes. , 1986, Archives of ophthalmology.

[59]  P. Witkovsky,et al.  Chapter 7 Neuron — Glia interaction in the brain and retina , 1985 .

[60]  E. Newman,et al.  Control of extracellular potassium levels by retinal glial cell K+ siphoning. , 1984, Science.

[61]  J F Ashmore,et al.  An analysis of transmission from cones to hyperpolarizing bipolar cells in the retina of the turtle. , 1983, The Journal of physiology.

[62]  C. Raine,et al.  Reinnervation of peripheral nerve segments implanted into the rat central nervous system , 1980, Brain Research.

[63]  B. Ehinger Glial and neuronal uptake of GABA, glutamic acid, glutamine and glutathione in the rabbit retina. , 1977, Experimental eye research.

[64]  M. Neal,et al.  The uptake ofl-glutamate by the retina , 1976, Brain Research.

[65]  M. Voaden,et al.  Glutamate metabolism in the frog retina , 1974, Nature.

[66]  S. Cajal,et al.  The Structure of the Retina , 1972 .

[67]  L. Zimmerman,et al.  Histopathology of juvenile retinoschisis. , 1968, Archives of ophthalmology.

[68]  A. Peters,et al.  The morphology of laminae A and A1 of the dorsal nucleus of the lateral geniculate body of the cat. , 1966, Journal of anatomy.

[69]  J. Szentágothai,et al.  The large glomerular synapse of the pulvinar. , 1965, Journal fur Hirnforschung.

[70]  W S Duke-Elder,et al.  THE STRUCTURE OF THE RETINA , 1926, The British journal of ophthalmology.

[71]  A. Dogiel Neuroglia der Retina des Menschen , 1893 .

[72]  H. Watts A Treatise on Chemistry , 1881, Nature.

[73]  H. Muller Zur Histologie der Netzhaut , 1851 .