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During electrochemical signal transmission through synapses, triggered by an action potential (AP), a stochastic number of synaptic vesicles (SVs), called the "quantal content," release neurotransmitters in the synaptic cleft. It is widely accepted that the quantal content probability distribution is a binomial based on the number of ready-release SVs in the presynaptic terminal. But the latter number itself fluctuates due to its stochastic replenishment, hence the actual distribution of quantal content is unknown. We show that exact distribution of quantal content can be derived for general stochastic AP inputs in the steady state. For fixed interval AP train, we prove that the distribution is a binomial, and corroborate our predictions by comparison with electrophysiological recordings from MNTB-LSO synapses of juvenile mice. For a Poisson train, we show that the distribution is nonbinomial. Moreover, we find exact moments of the quantal content in the Poisson and other general cases, which may be used to obtain the model parameters from experiments.
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http://dx.doi.org/10.1103/PhysRevLett.132.228401 | DOI Listing |
J Physiol
August 2025
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Ageing has been shown to affect both the structure and function of the neuromuscular junction (NMJ). In our previous study, we documented a biphasic change (first an increase followed by a decrease) in neurotransmission over the ageing time course at male mouse NMJs. Here, we explored several potential mechanisms behind the reduction in presynaptic neurotransmitter release in the later stages of ageing.
View Article and Find Full Text PDFInt Rev Neurobiol
July 2025
Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia. Electronic address:
Lambert Eaton Myasthenic Syndrome (LEMS) is a pre-synaptic neuromuscular junction disorder characterised clinically by leg-predominant proximal weakness with spread of weakness distally and cranially with increasing severity as well as reduced reflexes and autonomic symptoms such as a dry mouth. Typical electrophysiological findings include small compound muscle action potentials at rest that augment following short exercise, decrement at low frequency (2-5 Hz) repetitive nerve stimulation, and increment at high frequency (20-50 Hz) repetitive nerve stimulation. Immunologically, antibodies to voltage gated calcium channels are present in the majority of patients.
View Article and Find Full Text PDFDev Neurobiol
July 2025
Molecular, Cellular, and Developmental Biology Department, Yale University, New Haven, Connecticut, USA.
Numb is an adaptor protein with functions that include the endocytic processing of activated growth factor receptors. As growth factor signaling contributes to the development and function of the Drosophila neuromuscular junction (NMJ), we examined whether Numb is present at the larval NMJ and whether it is required for the growth, physiology, and/or plasticity of this synapse. Antisera prepared against Numb protein labeled NMJ presynaptic boutons, and RNAi knockdown of Numb, when directed to the presynaptic side, reduced the size of the NMJ.
View Article and Find Full Text PDFNeurochem Int
September 2025
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy. Electronic address:
Serotonergic modulation of pain transmission in the spinal cord involves the activation of multiple receptor types, including 5-HT receptors. Activation of spinal 5-HT receptors appears to have a predominant antinociceptive effect in various animal models. Although the serotonergic modulation of dorsal horn circuits has been extensively investigated, information about the specific effects of serotonergic receptors on identified neuron types remains limited.
View Article and Find Full Text PDFFront Cell Dev Biol
May 2025
Department of Cell and Developmental Biology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Mast cells (MCs) are sentinel cells of the immune system that play important protective roles in innate host defenses but are also key effectors of allergic responses and chronic inflammatory diseases. Both physiological and pathophysiological responses of MCs are mediated by the release of inflammatory mediators, many of which are stored, preformed, in secretory granules (SGs), and released by regulated exocytosis in response to multiple stimuli. MC SGs belong to the family of lysosome related organelles (LROs), as indicated by their content of lysosomal hydrolases, lysosomal membrane proteins and acidic pH.
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