Abstract
Most glutamatergic synapses in the mammalian central nervous system are covered by thin astroglial processes that exert a dual action on synaptically released glutamate: they form physical barriers that oppose diffusion and they carry specific transporters that remove glutamate from the extracellular space. The present study was undertaken to investigate the dual action of glia by means of computer simulation. A realistic synapse model based on electron microscope data and Monte Carlo algorithms were used for this purpose. Results show (1) that physical obstacles formed by glial processes delay glutamate exit from the cleft and (2) that this effect is efficiently counteracted by glutamate uptake. Thus, depending on transporter densities, the presence of perisynaptic glia may result in increased or decreased glutamate transient in the synaptic cleft. Changes in temporal profiles of cleft glutamate concentration induced by glia differentially impact the response of the various synaptic and perisynaptic receptor subtypes. In particular, GluN2B- and GluN2C-NMDA receptor responses are strongly modified while GluN2A-NMDA receptor responses are almost unaffected. Thus, variations in glial transporter expression may allow differential tuning of NMDA receptors according to their subunit composition. In addition, simulation data suggest that the sink effect generated by transporters accumulation in the vicinity of the release site is the main mechanism limiting glutamate spill-out. Physical obstacles formed by glial processes play a comparatively minor role.
Highlights
Most glutamatergic synapses in the mammalian central nervous system (CNS) are covered by thin astroglial processes that form the so-called perisynaptic glia
Detailed quantitative information provided by electron microscope data was used to construct a complex diffusion space as close as possible to the one existing at actual synapses
Recent data obtained by comparing the effects of tissue processing by aldehyde fixation and high-pressure freezing on the same type of synapses indicate that the shrinkage induced by aldehyde fixation does not affect cleft width [22]
Summary
Most glutamatergic synapses in the mammalian central nervous system (CNS) are covered by thin astroglial processes that form the so-called perisynaptic glia. Electron microscope studies indicate that the fine structure of perisynaptic glia is extremely variable [1]. Glial processes may either wrap the entire synaptic diameter or only a part of it, and extend to various degrees over the pre and post synaptic elements. The nucleus tractus solitarii (NTS) a brainstem nucleus receiving visceral sensory information, contains both single synapses and multisynaptic arrangements. We showed that the glial coverage of single NTS synapses was 68% of the synaptic diameter on average but could vary from none to a nearly complete one [4]
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