The connection strength of most chemical synapses changes dynamically during normal use as a function of the recent history of activity. The phenomenon is known as short-term synaptic plasticity or synaptic dynamics, and is thought to be involved in processing and filtering information as it is transmitted across the synaptic cleft. Multiple presynaptic mechanisms have been implicated, but large gaps remain in our understanding of how the mechanisms are modulated and how they interact. One important factor is the timing of recruitment of synaptic vesicles to a readily-releasable pool. A number of studies have concluded that activity and/or residual Ca can accelerate the mechanism, but alternative explanations for some of the evidence have emerged. Here I review the methodology that we have developed for isolating the recruitment and the dependence on activity from other kinds of mechanisms that are activated concurrently.
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http://dx.doi.org/10.3389/fnsyn.2019.00032 | DOI Listing |
Sci Adv
January 2025
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.
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January 2025
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Synapses are organized by trans-synaptic adhesion molecules that coordinate assembly of pre- and postsynaptic specializations, which, in turn, are composed of scaffolding proteins forming liquid-liquid phase-separated condensates. Presynaptic teneurins mediate excitatory synapse organization by binding to postsynaptic latrophilins; however, the mechanism of action of teneurins, driven by extracellular domains evolutionarily derived from bacterial toxins, remains unclear. In this work, we show that only the intracellular sequence, a dimerization sequence, and extracellular bacterial toxin-derived latrophilin-binding domains of Teneurin-3 are required for synapse organization, suggesting that teneurin-induced latrophilin clustering mediates synaptogenesis.
View Article and Find Full Text PDFCurr Biol
January 2025
Department of Neuroscience, Physiology & Pharmacology, UCL, Gower Street, London WC1E 6BT, UK. Electronic address:
Animals construct diverse behavioral repertoires by moving a limited number of body parts with varied kinematics and patterns of coordination. There is evidence that distinct movements can be generated by changes in activity dynamics within a common pool of motoneurons or by selectively engaging specific subsets of motoneurons in a task-dependent manner. However, in most cases, we have an incomplete understanding of the patterns of motoneuron activity that generate distinct actions and of how upstream premotor circuits select and assemble such motor programs.
View Article and Find Full Text PDFMol Psychiatry
January 2025
Icahn School of Medicine at Mount Sinai, Departments of Neuroscience, Psychiatry; Addiction Institute of Mount Sinai, New York, NY, USA.
Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.
View Article and Find Full Text PDFNeuron
January 2025
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:
Neurexin cell-adhesion molecules regulate synapse development and function by recruiting synaptic components. Here, we uncover a mechanism for presynaptic assembly that precedes neurexin recruitment, mediated by interactions between cytosolic proteins and membrane phospholipids. Developmental imaging in C.
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