Abstract
Electron microscopy has revealed an abundance of material in the clefts of synapses in the mammalian brain, and the biochemical and functional characteristics of proteins occupying synaptic clefts are well documented. However, the detailed spatial organization of the proteins in the synaptic clefts remains unclear. Electron microscope tomography provides a way to delineate and map the proteins spanning the synaptic cleft because freeze substitution preserves molecular details with sufficient contrast to visualize individual cleft proteins. Segmentation and rendering of electron dense material connected across the cleft reveals discrete structural elements that are readily classified into five types at excitatory synapses and four types at inhibitory synapses. Some transcleft elements resemble shapes and sizes of known proteins and could represent single dimers traversing the cleft. Some of the types of cleft elements at inhibitory synapses roughly matched the structure and proportional frequency of cleft elements at excitatory synapses, but the patterns of deployments in the cleft are quite different. Transcleft elements at excitatory synapses were often evenly dispersed in clefts of uniform (18 nm) width but some types show preference for the center or edges of the cleft. Transcleft elements at inhibitory synapses typically were confined to a peripheral region of the cleft where it narrowed to only 6 nm wide. Transcleft elements in both excitatory and inhibitory synapses typically avoid places where synaptic vesicles attach to the presynaptic membrane. These results illustrate that elements spanning synaptic clefts at excitatory and inhibitory synapses consist of distinct structures arranged by type in a specific but different manner at excitatory and inhibitory synapses.
Highlights
Synaptic formation, maintenance, and plasticity rely on coordination between multiple types of structural proteins spanning the synaptic cleft, the gap separating the pre- and postsynaptic membranes (Rees et al, 1976; Peters et al, 1991; Yamagata et al, 2003; Missler et al, 2012)
Synaptic cleft signaling regulates the recruitment of synaptic vesicles to the presynaptic active zone (Gottmann, 2008) while EphrinB promotes the recruitment of glutamate receptors and postsynaptic scaffolding proteins to the synapse (Waites et al, 2005)
Electron microscope tomography of intact hippocampal culture synapses reveals five types of discrete elements crossing the synaptic cleft at excitatory synapses
Summary
Synaptic formation, maintenance, and plasticity rely on coordination between multiple types of structural proteins spanning the synaptic cleft, the gap separating the pre- and postsynaptic membranes (Rees et al, 1976; Peters et al, 1991; Yamagata et al, 2003; Missler et al, 2012). These transcleft proteins comprise a diverse group of molecules, with the most proteins being members of the cadherin (Tepass et al, 2000) and immunoglobin (Rougon and Hobert, 2003) superfamilies. Neurexin/neuroligin complexes work in conjunction with N-cadherin in order to regulate synaptic density during the initial stages of synaptogenesis (Aiga et al, 2011)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
