Neurotransmitter release is well known to occur at specialized synaptic regions that include presynaptic active zones and postsynaptic densities. At cholinergic synapses in the chick ciliary ganglion, however, membrane formations and physiological measurements suggest that release distant from postsynaptic densities can activate the predominantly extrasynaptic alpha7 nicotinic receptor subtype. We explored such ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. Simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.
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http://dx.doi.org/10.1126/science.1108239 | DOI Listing |
Nat Commun
January 2025
Freie Universität Berlin, Institute for Biology and Genetics, Berlin, Germany.
At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional Drosophila AZ protein, "Blobby", essential for proper AZ nano-organization.
View Article and Find Full Text PDFCell Rep
October 2024
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA. Electronic address:
Cell Rep
February 2024
Department of Neurobiology, University of Utah, Salt Lake City, UT 84112-9458, USA. Electronic address:
N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors have essential roles in neurotransmission and synaptic plasticity. Previously, we identified an evolutionarily conserved protein, NRAP-1, that is required for NMDA receptor (NMDAR) function in C. elegans.
View Article and Find Full Text PDFbioRxiv
December 2023
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520.
Non-spiking sensory hair cells of the auditory and vestibular systems encode a dynamic range of graded signals with high fidelity by vesicle exocytosis at ribbon synapses. Ribeye, the most abundant protein in the synaptic ribbon, is composed of a unique A domain specific for ribbons and a B-domain nearly identical to the transcriptional corepressor CtBP2. CTBP2 and the B-domain of Ribeye contain a surface cleft that binds to proteins harboring a PXDLS/T peptide motif.
View Article and Find Full Text PDFFront Cell Neurosci
November 2023
Animal Physiology/Neurobiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Vision is our primary sense, and maintaining it throughout our lifespan is crucial for our well-being. However, the retina, which initiates vision, suffers from an age-related, irreversible functional decline. What causes this functional decline, and how it might be treated, is still unclear.
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