Biophys J, July 2002, p. 125-134, Vol. 83, No. 1

Asymmetry of Glia near Central Synapses Favors Presynaptically Directed Glutamate Escape

Knut Petter Lehre^* and Dmitri A. Rusakov^*

 ^*Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom, and  Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway

Recent findings demonstrate that synaptically released excitatory neurotransmitter glutamate activates receptors outside the immediate synaptic cleft and that the extent of such extrasynaptic actions is regulated by the high affinity glutamate uptake. The bulk of glutamate transporter systems are evenly distributed in the synaptic neuropil, and it is generally assumed that glutamate escaping the cleft affects pre- and postsynaptic receptors to a similar degree. To test whether this is indeed the case, we use quantitative electron microscopy and establish the stochastic pattern of glial occurrence in the three-dimensional (3D) vicinity of two common types of excitatory central synapses, stratum radiatum synapses in hippocampus and parallel fiber synapses in cerebellum. We find that the occurrence of glia postsynaptically is strikingly higher (3-4-fold) than presynaptically, in both types of synapses. To address the functional consequences of this asymmetry, we simulate diffusion and transport of synaptically released glutamate in these two brain areas using a detailed 3D compartmental model of the extracellular space with glutamate transporters arranged unevenly, in accordance with the obtained experimental data. The results predict that glutamate escaping the synaptic cleft is 2-4 times more likely to activate presynaptic compared to postsynaptic receptors. Simulations also show that postsynaptic neuronal transporters (EAAT4 type) at dendritic spines of cerebellar Purkinje cells exaggerate this asymmetry further. Our data suggest that the perisynaptic environment of these common central synapses favors fast presynaptic feedback in the information flow while preserving the specificity of the postsynaptic input.

Biophys J, July 2002, p. 125-134, Vol. 83, No. 1
© 2002 by the Biophysical Society   0006-3495/02/07/125/10  $2.00

This article has been cited by other articles:

				K. K. Murai and D. J. Van Meyel Neuron Glial Communication at Synapses: Insights From Vertebrates and Invertebrates Neuroscientist, December 1, 2007; 13(6): 657 - 666. [Abstract] [PDF]

				D. A. Rusakov, F. Saitow, K. P. Lehre, and S. Konishi Modulation of Presynaptic Ca2+ Entry by AMPA Receptors at Individual GABAergic Synapses in the Cerebellum J. Neurosci., May 18, 2005; 25(20): 4930 - 4940. [Abstract] [Full Text] [PDF]

				A. Scimemi, A. Fine, D. M. Kullmann, and D. A. Rusakov NR2B-Containing Receptors Mediate Cross Talk among Hippocampal Synapses J. Neurosci., May 19, 2004; 24(20): 4767 - 4777. [Abstract] [Full Text] [PDF]

				Y. V. Pankratov and O. A. Krishtal Distinct Quantal Features of AMPA and NMDA Synaptic Currents in Hippocampal Neurons: Implication of Glutamate Spillover and Receptor Saturation Biophys. J., November 1, 2003; 85(5): 3375 - 3387. [Abstract] [Full Text] [PDF]

				A. Bordey and H. Sontheimer Modulation of Glutamatergic Transmission by Bergmann Glial Cells in Rat Cerebellum In Situ J Neurophysiol, February 1, 2003; 89(2): 979 - 988. [Abstract] [Full Text] [PDF]