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      Release probability of hippocampal glutamatergic terminals scales with the size of the active zone

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          Abstract

          Cortical synapses display remarkable structural, molecular and functional heterogeneity. Our knowledge regarding the relationship between the ultrastructural and functional parameters is still fragmented. Here we asked how the release probability and presynaptic [Ca 2+] transients relate to the ultrastructure of rat hippocampal glutamatergic axon terminals. Two-photon Ca 2+ imaging-derived optical quantal analysis and correlated electron microscopic reconstructions revealed a tight correlation between the release probability and the active zone area. The peak amplitude of [Ca 2+] transients in single boutons also positively correlated with the active zone area. Freeze-fracture immunogold labeling revealed that the voltage-gated Ca 2+ channel subunit Cav2.1 and the presynaptic protein Rim1/2 are confined to the active zone and their numbers scale linearly with the active zone area. Gold particles for Cav2.1 showed a nonrandom distribution within the active zones. Our results demonstrate that the number of several active zone proteins, including presynaptic Ca 2+ channels, docked vesicles and the release probability scales linearly with the active zone area.

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          Quantitative ultrastructural analysis of hippocampal excitatory synapses.

          T Schikorski, C F Stevens (1997)
          From three-dimensional reconstructions of CA1 excitatory synapses in the rodent hippocampus and in culture, we have estimated statistical distributions of active zone and postsynaptic density (PSD) sizes (average area approximately 0.04 micron2), the number of active zones per bouton (usually one), the number of docked vesicles per active zone (approximately 10), and the total number of vesicles per bouton (approximately 200), and we have determined relationships between these quantities, all of which vary from synapse to synapse but are highly correlated. These measurements have been related to synaptic physiology. In particular, we propose that the distribution of active zone areas can account for the distribution of synaptic release probabilities and that each active zone constitutes a release site as identified in the standard quantal theory attributable to Katz (1969).
          Article 0 comments Cited 203 times – based on 0 reviews     Review now
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            Nanodomain coupling between Ca²⁺ channels and sensors of exocytosis at fast mammalian synapses.

            E Eggermann, Peter Jonas, Iancu Bucurenciu … (2011)
            The physical distance between presynaptic Ca(2+) channels and the Ca(2+) sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca(2+) channels that are coupled to Ca(2+) sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein-protein interactions involving Ca(2+) channels, Ca(2+) sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission.
            Article 0 comments Cited 158 times – based on 0 reviews     Review now
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              Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus.

              J. Roberts, R Lujan, G Laube … (1998)
              It has been suggested that some glutamatergic synapses lack functional AMPA receptors. We used quantitative immunogold localization to determine the number and variability of synaptic AMPA receptors in the rat hippocampus. Three classes of synapses show distinct patterns of AMPA receptor content. Mossy fiber synapses on CA3 pyramidal spines and synapses on GABAergic interneurons are all immunopositive, have less variability, and contain 4 times as many AMPA receptors as synapses made by Schaffer collaterals on CA1 pyramidal spines and by commissural/ associational (C/A) terminals on CA3 pyramidal spines. Up to 17% of synapses in the latter two connections are immunonegative. After calibrating the immunosignal (1 gold = 2.3 functional receptors) at mossy synapses of a 17-day-old rat, we estimate that the AMPA receptor content of C/A synapses on CA3 pyramidal spines ranges from <3 to 140. A similar range is found in adult Schaffer collateral and C/A synapses.
              Article 0 comments Cited 150 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9809671
                Journal ID (pubmed-jr-id): 21092
                Journal ID (nlm-ta): Nat Neurosci
                Journal ID (iso-abbrev): Nat. Neurosci.
                Title: Nature neuroscience
                ISSN (Print): 1097-6256
                ISSN (Electronic): 1546-1726
                Publication date Nihms-submitted: 16 May 2012
                Publication date (Electronic): 10 June 2012
                Publication date PMC-release: 01 January 2013
                Volume: 15
                Issue: 7
                Pages: 988-997
                Affiliations
                [1 ]Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, HUNGARY
                [2 ]Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, HUNGARY
                [3 ]Institute of Anatomy and Cell Biology, Department of Neuroanatomy, Department of Physiology II, University of Freiburg, Freiburg, Germany
                [4 ]BIOSS Centre for Biological Studies, University of Freiburg, Freiburg, Germany
                [5 ]Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
                Author notes
                Correspondence to: Zoltan Nusser, Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony Street 43, 1083 Budapest, HUNGARY Tel.: 36 1 210 9983, Fax: 36 1 210 9984, nusser@ 123456koki.hu
                Article
                Manuscript ID: UKMS48348
                DOI: 10.1038/nn.3137
                PMC ID: 3386897
                PubMed ID: 22683683
                SO-VID: 1082f36c-e13b-40fc-8d5f-2f0a6e6971f4
                License:

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: Wellcome Trust :
                Award ID: 094513 || WT
                Funded by: Wellcome Trust :
                Award ID: 090197 || WT
                Funded by: Wellcome Trust :
                Award ID: 083484 || WT
                Categories
                Subject: Article

                ScienceOpen disciplines: Neurosciences
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                ScienceOpen disciplines: Neurosciences

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