A theory of synaptic transmission

Abstract

Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters within just milliseconds of the action potential. Yet neurotransmitter release lacks a theoretical framework that is both phenomenologically accurate and mechanistically realistic. Here, we present an analytic theory of the action-potential-triggered neurotransmitter release at the chemical synapse. The theory is demonstrated to be in detailed quantitative agreement with existing data on a wide variety of synapses from electrophysiological recordings in vivo and fluorescence experiments in vitro. Despite up to ten orders of magnitude of variation in the release rates among the synapses, the theory reveals that synaptic transmission obeys a simple, universal scaling law, which we confirm through a collapse of the data from strikingly diverse synapses onto a single master curve. This universality is complemented by the ability of the theory to readily extract, through a fit to the data, the kinetic and energetic parameters that uniquely identify each synapse. The theory provides a means to detect cooperativity among the SNARE complexes that mediate vesicle fusion and reveals such cooperativity in several existing data sets. The theory is further applied to establish connections between molecular constituents of synapses and synaptic function. The theory allows competing hypotheses of short-term plasticity to be tested and identifies the regimes where particular mechanisms of synaptic facilitation dominate or, conversely, fail to account for the existing data for the paired-pulse ratio. The derived trade-off relation between the transmission rate and fidelity shows how transmission failure can be controlled by changing the microscopic properties of the vesicle pool and SNARE complexes. The established condition for the maximal synaptic efficacy reveals that no fine tuning is needed for certain synapses to maintain near-optimal transmission. We discuss the limitations of the theory and propose possible routes to extend it. These results provide a quantitative basis for the notion that the molecular-level properties of synapses are crucial determinants of the computational and information-processing functions in synaptic transmission.

The nonlinear meccano of hyperactivity in Alzheimer

“…We thus set to characterize the admissible states in AD emergence by including in our model of glutamate-mediated hyperactivity an effective description of Ca 2+ dependent Aβ build-up (De Caluwé and Dupont, 2013, and Supplementary Text Section ?? ) and considering two different scenarios of Ca 2+ affinity of synaptic release ( K R ) and activity-dependent Ca 2+ signaling ( η C ) that could be representative of the heterogeneity of cortical synaptic circuits (van Oostrum et al, 2023; Wang and Dudko, 2021; Zhu et al, 2018, and Supplementary Text Section ?? ).…”

“…The modeling framework introduced in this study helps address this question, providing a mathematical characterization of the rules governing the complex interplay between intrinsic and extrinsic properties of this highly specific regional and cellular vulnerability to AD. Including this framework in current data-driven approaches for AD monitoring (Chen et al, 2021; Wang, Li, et al, 2021; Huang et al, 2020) will ultimately serve to refine diagnosis, help explain the molecular mechanisms of AD development and progression, and reveal potential compensatory mechanisms to bolster resilience.…”

How Merkel cells transduce mechanical stimuli: A biophysical model of Merkel cells

“…Then we assume that the vesicle synthesis rate is inversely related to the number of vesicles. The exocytosis rate increases with the cytoplasm Ca 2+ concentration [ 20 ], and is positively correlated with the number of vesicles. Thus the dynamic equation of vesicles can be written as where n ve is the number of vesicles, k ve and k exo are the rate constants.…”

High Frequency Electromagnetic Radiation Stimulates Neuronal Growth and Hippocampal Synaptic Transmission

“…We found that 0.138 THz radiation to the hippocampal CA1 region for 60 min, and PSP amplitude in the CA1 region, were correlated with the terahertz radiation time. This phenomenon may be related to receptor dynamics, where the magnitude of the synaptic response is directly dependent on the amount of receptor activation [ 57 ]. Thus, PSP amplitude can characterize changes in the neurotransmitter release amount, the number of receptors, and the number of neurotransmitter–receptor bindings [ 58 , 59 , 60 ].…”