The Nanoscopic Organization of Synapse Structures: A Common Basis for Cell Communication

Abstract

Synapse structures, including neuronal and immunological synapses, can be seen as the plasma membrane contact sites between two individual cells where information is transmitted from one cell to the other. The distance between the two plasma membranes is only a few tens of nanometers, but these areas are densely populated with functionally different proteins, including adhesion proteins, receptors, and transporters. The narrow space between the two plasma membranes has been a barrier for resolving the synaptic architecture due to the diffraction limit in conventional microscopy (~250 nm). Various advanced super-resolution microscopy techniques, such as stimulated emission depletion (STED), structured illumination microscopy (SIM), and single-molecule localization microscopy (SMLM), bypass the diffraction limit and provide a sub-diffraction-limit resolving power, ranging from 10 to 100 nm. The studies using super-resolution microscopy have revealed unprecedented details of the nanoscopic organization and dynamics of synaptic molecules. In general, most synaptic proteins appear to be heterogeneously distributed and form nanodomains at the membranes. These nanodomains are dynamic functional units, playing important roles in mediating signal transmission through synapses. Herein, we discuss our current knowledge on the super-resolution nanoscopic architecture of synapses and their functional implications, with a particular focus on the neuronal synapses and immune synapses.

All-optical visualization of specific molecules in the ultrastructural context of brain tissue

“…; N = 4 experiments; n = 44 synaptic profiles; Fig. 2n), which is consistent with the range of pre-and post-synaptic density distance measurements determined previously by super-resolution microscopy and electron tomography (Valtschanoff et al, 2001;Dani et al, 2010;Acuna et al, 2016;Hao et al, 2021;Yang and Annaert, 2021). Similarly, dividing the distance between neighboring DPs by the nuclear expansion factor, we obtained a value of 67.2 ± 15.4 nm (mean ± s.d.…”

Ascorbic acid does not necessarily interfere with the electrochemical detection of dopamine

“…However, the presence of AA interferes with neurotransmitter detection due to its oxidation potential overlapping with the analyte-of-interest. Although dopamine concentration in the vicinity of synaptic cleft may be up to 1 μM 4 , we must note that the volume of synaptic cleft is exceedingly small ( 0.0018 μm 3 calculated by us based on synaptic cleft width being 25 nm 5 and synaptic apposition surface area being 0.058–0.089 μm 2 6 , 7 ), which causes dopamine concentration to dilute rapidly as a function of distance from synaptic cleft. Thus, AA concentration can be 200–10,000 fold higher than dopamine concentration at the electrode surface, assuming the AA concentration being 200 μM in vitro 8 and 100–250 μM in vivo 9 .…”

From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies

“…The tumor-stroma crosstalk eventually leads to the increased robustness of the tumor. A hypothesis was put forward [51] that such interactions include the formation of synapses and synapse-like structures with the interacting cells positioned at a distance of 10-30 nm [74]. Such a tight intercellular space could enhance the paracrine cross-communication.…”