Accessible Requires Authentication Published by De Gruyter December 5, 2019

Synapses: Multitasking Global Players in the Brain

Joachim H. R. Lübke ORCID logo and Astrid Rollenhagen
From the journal Neuroforum

Abstract

Synapses are key elements in the communication between neurons in any given network of the normal adult, developmental and pathologically altered brain. Synapses are composed of nearly the same structural subelements: a presynaptic terminal containing mitochondria with an ultrastructurally visible density at the pre- and postsynaptic apposition zone. The presynaptic density is composed of a cocktail of various synaptic proteins involved in the binding, priming and docking of synaptic vesicles inducing synaptic transmission. Individual presynaptic terminals (synaptic boutons) contain a couple of hundred up to thousands of synaptic vesicles. The pre- and postsynaptic densities are separated by a synaptic cleft. The postsynaptic density, also containing various synaptic proteins and more importantly various neurotransmitter receptors and their subunits specifically composed and arranged at individual synaptic complexes, reside at the target structures of the presynaptic boutons that could be somata, dendrites, spines or initial segments of axons.

Beside the importance of the network in which synapses are integrated, their individual structural composition critically determines the dynamic properties within a given connection or the computations of the entire network, in particular, the number, size and shape of the active zone, the structural equivalent to a functional neurotransmitter release site, together with the size and organization of the three functionally defined pools of synaptic vesicles, namely the readily releasable, the recycling and the resting pool, are important structural subelements governing the ‘behavior’ of synaptic complexes within a given network such as the cortical column.

In the late last century, neuroscientists started to generate quantitative 3D-models of synaptic boutons and their target structures that is one possible way to correlate structure with function, thus allowing reliable predictions about their function. The re-introduction of electron microscopy (EM) as an important tool achieved by modern high-end, high-resolution transmission-EM, focused ion beam scanning-EM, CRYO-EM and EM-tomography have enormously improved our knowledge about the synaptic organization of the brain not only in various animal species, but also allowed new insights in the ‘microcosms’ of the human brain in health and disease.

Zusammenfassung

Synapsen sind Schlüsselelemente der Kommunikation zwischen Neuronen in jedem beliebigen Netzwerk des normal adulten, sich entwickelnden, bzw. krankhaft veränderten Gehirns. Synapsen sind nahezu aus den gleichen strukturellen Subelementen aufgebaut: einem präsynaptischen Element, welches Mitochondrien und eine ultrastrukturell sichtbare Proteinverdichtung der Membran mit einem Cocktail verschiedener synaptischer Proteine enthält, welche für die Bindung‚ das „Priming“ und das Andocken synaptischer Vesikel verantwortlich sind. Das präsynaptische Terminal (synaptischer Bouton) kann einige hundert bis zu einigen tausend synaptische Vesikel enthalten. Die präsynaptische Seite ist durch den synaptischen Spalt von der postsynaptischen Dichte der Zielstruktur getrennt, die entweder Somata, Dendriten, dendritische „Spines“ oder Axoninitialsegmente darstellen. Die postsynaptische Dichte enthält wiederum spezifische synaptische Proteine, aber noch wichtiger verschiedene Neurotransmitter-Rezeptoren und deren Untereinheiten, die je nach Synapsentyp individuell komponiert und arrangiert sind.

Zum Ende des letzten Jahrhunderts wurde begonnen quantitative 3D-Modelle synaptischer Boutons und deren Zielstrukturen zu generieren, welches eine Möglichkeit darstellt korrelierte Struktur/Funktions-Beziehungen herzustellen. In anderen Worten: erlaubt die strukturelle Komposition von Synapsen verlässliche Voraussagen zu ihrer Funktion?

Die „Wiederentdeckung“ der Elektronmikroskopie (EM) als ein wichtiges Instrument hat mittels hochmoderner, hochauflösender Transmission-EM, der Einführung der „Focused Ion Beam Scanning-EM“ Technologie, die Etablierung von CRYO-EM sowie EM-Tomographie zu einem enormen Erkenntnisgewinn der synaptischen Organisation in verschiedenen Tiermodellen, aber auch zu neuen Erkenntnissen im „Mikrokosmos“ des gesunden und erkrankten menschlichen Gehirns geführt.

Acknowledgements

The authors are very grateful to all past and present members of the Group ‘Structure of Synapses’ at the INM-10 and INM-2, Research Centre Jülich GmbH for their individual contributions that made this review possible. We would also like to thank our collaborator Dr. Mike Hasenberg and his team at the IMCES Electron Microscopy Unit (EMU), Medical Research Centre, University Hospital Essen for their constant support with FIB-SEM and EM tomography. Finally, many thanks to Dr. Dorothea Miller and Priv. Doz. Dr. Marec von Lehe, Department of Neurosurgery, Knappschaftskrankenhaus Bochum and Brandenburg Medical School, Ruppiner Clinics, Neuruppin for providing the human tissue samples. Finally, the funding by the Helmholtz-Society and Deutsche Forschungsgemeinschaft is very much acknowledged.

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Published in Print: 2020-02-25

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