Advances in imaging ultrastructure yield new insights into presynaptic biology

Abstract

Synapses are the fundamental functional units of neural circuits, and their dysregulation has been implicated in diverse neurological disorders. At presynaptic terminals, neurotransmitter-filled synaptic vesicles are released in response to calcium influx through voltage-gated calcium channels activated by the arrival of an action potential. Decades of electrophysiological, biochemical, and genetic studies have contributed to a growing understanding of presynaptic biology. Imaging studies are yielding new insights into how synapses are organized to carry out their critical functions. The development of techniques for rapid immobilization and preservation of neuronal tissues for electron microscopy (EM) has led to a new renaissance in ultrastructural imaging that is rapidly advancing our understanding of synapse structure and function.

Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

“…Differences observed in CB 1 ‐KO relative to CB 1 ‐WT could be particularly relevant as the synaptic vesicle distribution in CB 1 ‐KO could affect the exposure of synaptic vesicles to the calcium sources that dictate vesicle dynamics (Böhme, Grasskamp, & Walter, ; Guerrier & Holcman, ) that are crucial for synaptic plasticity (Atwood, Lovinger, & Mathur, ; Böhme et al, ; Chen, Das, Nakamura, DiGregorio, & Young, ; Eggermann, Bucurenciu, Goswami, & Jonas, ; Guerrier & Holcman, ; Holderith et al, ; Indriati et al, ; Keller et al, ; Sheng et al, ). The structural basis of synaptic plasticity is mediated by the dynamics of the presynaptic architecture (Bruckner, Zhan, & O'Connor‐Giles, ). In this respect, changes in synaptic strength induced by cannabinoids might reflect a reduction in the readily releasable pool, as short‐time synaptic depression is typically attributed to some depletion of this vesicle pool (Schneggenburger, Sakaba, & Neher, ; Zucker & Regehr, ).…”

Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

“…The active zone cytomatrix of the Drosophila NMJ is readily observed in electron micrographs of conventional chemically fixed preparations as a T-shaped electron density, often referred to as a T-bar, projecting from the active zone membrane into the bouton interior. At the ultrastructural level, the conserved proteins of the active zone cytomatrix adopt distinct structures at different synapses both within and between species (Zhai and Bellen, 2004;Bruckner et al, 2015). These structural differences likely reflect the distinct functions and release properties of these synapses and imply an important relationship between cytomatrix structure and synaptic function.…”

BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission

“…Electron–dense projections are a prominent feature of active zones in electron micrographs. These electron-dense projections contain cytomatrix proteins that function in the clustering of readily releasable synaptic vesicles in close proximity to Ca 2+ channels in order to coordinate synchronized release ( Bruckner et al, 2015 ; Wichmann and Sigrist, 2010 ). Thus, the proper formation of dense projections is a key determinant of neurotransmitter release at active zones.…”