Significance Release of neurotransmitters relies on submillisecond coupling synaptic vesicle fusion to the triggering signal: AP-evoked presynaptic Ca 2+ influx. The key player that controls exocytosis is sensor synaptotagmin 1 (Syt1). While activation Syt1 has been extensively characterized, how reversibly clamps vesicular remains enigmatic. Here, using a targeted mutation combined with fluorescence imaging and electrophysiology, we show structural feature self-oligomerize provides...

Abstract The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties neuronal synapses regulation network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular tens to hundreds individual synaptic outputs from pyramidal cells with 4 millisecond temporal 75 nm spatial resolution. We find that...

We explain the mechanism that elicits mixed mode oscillations (MMOs) and subprimary firing range we recently discovered in mouse spinal motoneurons. In this regime, high-frequency subthreshold appear a few millivolts below spike voltage threshold precede of full blown spike. By combining intracellular recordings vivo (including dynamic clamp experiments) motoneurons modeling, show are due to currents MMOs each time membrane is low excitability state. Slow kinetic processes largely contribute...

Calcium ions are an important second messenger in living cells. Indeed, calcium signals the form of waves have been subject much recent experimental interest. It is now well established that these composed elementary stochastic release events (calcium puffs or sparks) from spatially localized stores. Here we develop a computationally inexpensive model release, based upon generalization fire-diffuse-fire threshold model. Our retains discrete nature stores, but also incorporates notion...

Significance Neurons fire action potentials to transfer information through synaptic release of neurotransmitter. At presynaptic terminals, the pattern potential discharge is integrated dynamic Ca 2+ signaling by machinery which triggers It generally accepted that rate and temporal precision firing support between neurons. Here, we show in contrast coding, giant mossy fiber terminals count number during trains trigger CA3 pyramidal cell firing. Our results shed light on signal mechanisms...

Action potential-dependent release of synaptic vesicles and short-term plasticity are dynamically regulated by the endogenous Ca(2+) buffers that shape [Ca(2+)] profiles within a presynaptic bouton. Calmodulin is one most abundant proteins it binds faster than any other characterized neuronal buffer. Direct effects calmodulin on fast dynamics vesicular however have not been studied in detail. Using experimentally constrained three-dimensional diffusion modeling influx-exocytosis coupling at...

Abstract Calcium-evoked release of neurotransmitters from synaptic vesicles (SVs) is catalysed by SNARE proteins. The predominant view that, at rest, complete assembly complexes inhibited (‘clamped’) synaptotagmin and complexin molecules. Calcium binding synaptotagmins releases this fusion clamp triggers fast SV exocytosis. However, model has not been quantitatively tested over physiological timescales. Here we describe an experimentally constrained computational modelling framework to...

Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity exocytosis timing and efficacy based on the recent history of activity. This is critical for information transfer brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions delineate minimal protein machinery sufficient account various modes...

Gap junctions, also referred to as electrical synapses, are expressed along the entire central nervous system and important in mediating various brain rhythms both normal pathological states. These connections can form between dendritic trees of individual cells. Many dendrites express membrane channels that confer on them a sub-threshold resonant dynamics. To obtain insight into modulatory role gap junctions tuning networks trees, we generalise "sum-over-trips" formalism for calculating...

We establish, from extensive numerical experiments, that the two dimensional stochastic fire-diffuse-fire model belongs to directed percolation universality class. This is an idealized of intracellular calcium release retains both discrete nature stores and release. It formed array noisy threshold elements are coupled only by a diffusing signal. The supports spontaneous events can merge form spreading circular spiral waves activity. critical level noise required for system exhibit...

Calcium is a crucial component in plethora of cellular processes involved cell birth, life, and death. Intercellular calcium waves that can spread through multiple cells provide one form communication mechanism between various parts tissues. Here we introduce simple, yet biophysically realistic model for the propagation intercellular based on fire-diffuse-fire type dynamics. release sites are considered to be discretely distributed along individual linear connected by gap junctions solution...

Neurons are characterised by a morphological structure unique amongst biological cells, the core of which is dendritic tree. The vast number geometries, combined with heterogeneous properties cell membrane, continue to challenge scientists in predicting neuronal input-output relationships, even case sub-threshold currents. Green's function obtained for given geometry provides this functional relationship passive or quasi-active dendrites and can be constructed sum-over-trips approach based...

Action potentials trigger two modes of neurotransmitter release, with a fast synchronous component and temporally delayed asynchronous release. Asynchronous release contributes to information transfer at synapses, including the hippocampal mossy fiber (MF) CA3 pyramidal cell synapse where it controls timing postsynaptic neuron firing. Here, we identified characterized main determinants MF-CA3 synapse. We found that synapses can last on order seconds following repetitive MF stimulation....

Renshaw cells (V1 R ) are excitable as soon they reach their final location next to the spinal motoneurons and functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling dynamical systems theory, we analyzed, for first time, mechanisms underlying electrophysiological properties of V1 during early embryonic development mouse cord locomotor networks (E11.5–E16.5). We found that these interneurons subdivided into several functional clusters from...

Neuronal networks connected by electrical synapses, also referred to as gap junctions, are present throughout the entire central nervous system. Many instances of gap-junctional coupling formed between dendritic arbours individual cells, and these dendro-dendritic junctions known play an important role in mediating various brain rhythms both normal pathological states. The dynamics such neuronal modelled passive or quasi-active (resonant) membranes can be described Green's function which...

Analytical forms for neuronal firing rates are important theoretical tools the analysis of network states. Since 1960s, majority approaches have treated neurons as being electrically compact and therefore isopotential. These yielded considerable insight into how single-cell properties affect activity; however, many classes, such cortical pyramidal cells, extended objects. Calculation complex flow electrical activity driven by stochastic spatio-temporal synaptic input streams in these...

Abstract Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation, but the patterns of activity required fire postsynaptic CA3 pyramidal neurons remain poorly understood. We show that count number spikes transmit information cells through a distinctive interplay between presynaptic calcium dynamics, buffering and vesicle replenishment. This identifies previously unexplored coding mechanism in brain.