22 research outputs found

    Bayesian Inference of Synaptic Quantal Parameters from Correlated Vesicle Release

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    Synaptic transmission is both history-dependent and stochastic, resulting in varying responses to presentations of the same presynaptic stimulus. This complicates attempts to infer synaptic parameters and has led to the proposal of a number of different strategies for their quantification. Recently Bayesian approaches have been applied to make more efficient use of the data collected in paired intracellular recordings. Methods have been developed that either provide a complete model of the distribution of amplitudes for isolated responses or approximate the amplitude distributions of a train of post-synaptic potentials, with correct short-term synaptic dynamics but neglecting correlations. In both cases the methods provided significantly improved inference of model parameters as compared to existing mean-variance fitting approaches. However, for synapses with high release probability, low vesicle number or relatively low restock rate and for data in which only one or few repeats of the same pattern are available, correlations between serial events can allow for the extraction of significantly more information from experiment: a more complete Bayesian approach would take this into account also. This has not been possible previously because of the technical difficulty in calculating the likelihood of amplitudes seen in correlated post-synaptic potential trains; however, recent theoretical advances have now rendered the likelihood calculation tractable for a broad class of synaptic dynamics models. Here we present a compact mathematical form for the likelihood in terms of a matrix product and demonstrate how marginals of the posterior provide information on covariance of parameter distributions. The associated computer code for Bayesian parameter inference for a variety of models of synaptic dynamics is provided in the supplementary material allowing for quantal and dynamical parameters to be readily inferred from experimental data sets

    The mechanisms underlying synaptic transmission at the layer 4 of sensory cortical areas

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    Die Neuronen in Schicht vier (L4) des cerebralen Kortex spielen eine wichtige Rolle bei der Signalübertragung vom Thalamus zu anderen Kortexbereichen. Das Verständnis der grundlegenden Eigenschaften der synaptischen Übertragung zwischen Neuronen in L4 ermöglicht es uns, ein klarerers Bild davon zu erhalten, wie die neuronalen Netzwerke in L4 kooperieren um sensorische Informationen zu verarbeiten. In dieser Studie haben wir für exzitatorische synaptische Verbindungen innerhalb der L4 des visuellen Kortexes (V1) sowie des somatosensorischen Kortexes (S1) der Maus Parameter untersucht, die die synaptische Stärke beeinflussen, wie quantale Größe (q), die Größe des schnell freisetzbaren Vesikelvorrats (N) und die Freisetzungswahrscheinlichkeit (Pr) Während unter physiologischen Bedingungen in V1-Synapsen nur ein Vesikel pro Freisetzungszone freigesetzt wird, wurde bei S1-Synapsen multivesikuläre Freisetzung (MVR) beobachtet. Darüber hinaus konnten wir eine Sättigung der postsynaptischen Rezeptoren bei S1-Synapsen feststellen. Die anderen gemessenen synaptischen Eigenschaften sind in beiden Kortexregionen ähnlich. Experimente mit Dynamic Clamp deuten darauf hin, dass die niedrigere Freisetzungswahrscheinlichkeit sowie die multivesikuläre Freisetzung bei S1-Synapsen dazu führen, dass weniger synaptische Erregungen genügen, um ein Aktionspotential in der postsynaptischen Zelle auszulösen. Zusätzlich dazu tragen der langsamere Abfall des synaptischen Stroms und die intrinsischen Membraneigenschaften der postsynaptischen Zelle zur verlässlichen Signalübertragung zwischen S1-Neuronen bei.Neurons in layer 4 (L4) of the cortex play an important role in transferring signals from thalamus to other layers of the cortex. Understanding the fundamental properties of synaptic transmission between L4 neurons helps us to gain a clear picture of how the neuronal network in L4 co-operates to process sensory information. In the present study, we have determined the underlying parameters that govern synaptic strength such as quantal size (q), size of readily releasable vesicle pool (N) and release probability (Pr) of excitatory synaptic connections within L4 of the visual cortex (V1) and the somatosensory cortex (S1) in mice. While only a single vesicle is released per release site under physiological conditions at V1 synapses, multivesicular release (MVR) is observed at S1 synapses. In addition, we observed a saturation of postsynaptic receptors at S1 synapses. Other synaptic properties are similar in both cortices. Dynamic clamp experiments suggest that higher Pr and MVR at S1 synapses lower the requirement of the number of synaptic inputs to generate postsynaptic action potentials. In addition, the slower decay of synaptic current and the intrinsic membrane properties of the postsynaptic neuron also contribute to the reliable transmission between S1 neurons

    High Bandwidth Synaptic Communication and Frequency Tracking in Human Neocortex

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    Neuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more efficient in transferring information between neurons than rodent synapses. To test this, we recorded from connected pairs of pyramidal neurons in acute brain slices of adult human and mouse temporal cortex and probed the dynamical properties of use-dependent plasticity. We found that human synaptic connections were purely depressing and that they recovered three to four times more swiftly from depression than synapses in rodent neocortex. Thereby, during realistic spike trains, the temporal resolution of synaptic information exchange in human synapses substantially surpasses that in mice. Using information theory, we calculate that information transfer between human pyramidal neurons exceeds that of mouse pyramidal neurons by four to nine times, well into the beta and gamma frequency range. In addition, we found that human principal cells tracked fine temporal features, conveyed in received synaptic inputs, at a wider bandwidth than for rodents. Action potential firing probability was reliably phase-locked to input transients up to 1,000 cycles/s because of a steep onset of action potentials in human pyramidal neurons during spike trains, unlike in rodent neurons. Our data show that, in contrast to the widely held views of limited information transfer in rodent depressing synapses, fast recovering synapses of human neurons can actually transfer substantial amounts of information during spike trains. In addition, human pyramidal neurons are equipped to encode high synaptic information content. Thus, adult human cortical microcircuits relay information at a wider bandwidth than rodent microcircuits

    Data‐driven integration of hippocampal CA1 synaptic physiology in silico

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    The anatomy and physiology of monosynaptic connections in rodent hippocampal CA1 have been extensively studied in recent decades. Yet, the resulting knowledge remains disparate and difficult to reconcile. Here, we present a data‐driven approach to integrate the current state‐of‐the‐art knowledge on the synaptic anatomy and physiology of rodent hippocampal CA1, including axo‐dendritic innervation patterns, number of synapses per connection, quantal conductances, neurotransmitter release probability, and short‐term plasticity into a single coherent resource. First, we undertook an extensive literature review of paired recordings of hippocampal neurons and compiled experimental data on their synaptic anatomy and physiology. The data collected in this manner is sparse and inhomogeneous due to the diversity of experimental techniques used by different groups, which necessitates the need for an integrative framework to unify these data. To this end, we extended a previously developed workflow for the neocortex to constrain a unifying in silico reconstruction of the synaptic physiology of CA1 connections. Our work identifies gaps in the existing knowledge and provides a complementary resource toward a more complete quantification of synaptic anatomy and physiology in the rodent hippocampal CA1 region

    Властивості квантового вивільнення глутамату та гліцину в синапсах між первинними аферентними нейронами та нейронами дорсального рога в кокультурі

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    З використанням методики „петч­клемп” реєстрували трансмембранні струми та потенціали в парах синаптично зв’язаних кокультивованих первинних аферентних нейронів (клітин спінальних гангліїв – СГ) та нейронів дорсальних рогів (ДР) спинного мозку щурів, визначаючи особливості вивільнення глутамату та гліцину у відповідних синапсах. Аналізуючи розподіли амплітуд постсинаптичних струмів, зареєстрованих у нейронах ДР, визначали квантові параметри викиду даних нейротрансмітерів. Показано, що вивільнення квантів нейротрансмітерів внаслідок надходження пресинаптичного потенціалу дії до синапсів глутамат­ та гліцинергічних нейронів СГ здійснюється незалежно. Ймовірність викиду трансмітера підпорядковується біноміальній статистиці. Є підстави вважати, що пресинаптичний нейрон СГ формує на постсинаптичній клітині ДР в умовах кокультури декілька синаптичних з’єднань. Зроблено висновок, що пресинаптичні терміналі даних синапсів можуть мати більше однієї зони вивільнення трансмітера; це не виключає можливості багатоквантового вивільнення гліцину або глутамату в декількох зонах викиду в процесі нейропередач

    Functional consequences of pre- and postsynaptic expression of synaptic plasticity

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    Growing experimental evidence shows that both homeostatic and Hebbian synaptic plasticity can be expressed presynaptically as well as postsynaptically. In this review, we start by discussing this evidence and methods used to determine expression loci. Next, we discuss the functional consequences of this diversity in pre- and postsynaptic expression of both homeostatic and Hebbian synaptic plasticity. In particular, we explore the functional consequences of a biologically tuned model of pre- and postsynaptically expressed spike-timing-dependent plasticity complemented with postsynaptic homeostatic control. The pre- and postsynaptic expression in this model predicts (i) more reliable receptive fields and sensory perception, (ii) rapid recovery of forgotten information (memory savings), and (iii) reduced response latencies, compared with a model with postsynaptic expression only. Finally, we discuss open questions that will require a considerable research effort to better elucidate how the specific locus of expression of homeostatic and Hebbian plasticity alters synaptic and network computations.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'

    Multiquantal Glutamate Release from Rod Photoreceptors

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    Neurons communicate via Ca2+-dependent release of neurotransmitters packaged into vesicles (quanta). Some CNS neurons, especially sensory synapses, can release multiple vesicles at a time, increasing information transmission and overcoming the unreliability of a stochastic process. Ribbon-bearing neurons, including retinal photoreceptors, face the challenge of encoding sensory receptor potentials into an ever-changing train of vesicle release events. We studied release of glutamate using voltage clamp to measure anion currents activated during glutamate reuptake into presynaptic terminals (IA(glu)) of salamander and mouse rods, finding that each employ distinct mechanisms for multiquantal release. In amphibian rods, we found that 1/3 of the spontaneous IA(glu) fusion events involve synchronous fusion of multiple vesicles. By varying intracellular buffering to localize Ca2+-dependent events, we found that multiquantal release occurs near Ca2+ sources. In photoreceptors, Ca2+ influx occurs just below synaptic ribbons. Vesicles house SNARE machinery so we hypothesized that vesicles on the ribbon undergo homotypic fusion prior to exocytosis. Destruction of ribbons and disruption of the SNARE-protein syntaxin3B prevented spontaneous multiquantal release, suggesting that salamander rods are capable of multivesicular release due to homotypic fusion of vesicles along ribbons. In mouse rods, spontaneous release at −70 mV involved the stochastic fusion of single vesicles. With depolarization, glutamate release increased linearly with voltage-gated Ca2+ currents. As the membrane approached the resting potential in darkness of −40 mV, rods began to release glutamate in multivesicular bursts of 17±7 vesicles every 2801±598 ms. Release evoked by brief depolarizations and bursts both involved the same pool of ribbon-associated vesicles with fusion regulated by the vesicular Ca2+ sensor synaptotagmin-1. A second, slower component of release controlled by synaptotagmin-7 is also present in rods but not cones. We hypothesized a v role for coordinated bursts of release in transmitting single photon signals. The rate of bursting was responsive to small voltage changes of 1.0-3.5 mV and the voltage waveform that triggered bursts most effectively was similar to single photon responses. We propose that multiquantal bursts contribute to mechanisms that filter out small noisy events to improve reliable detection of single photons by the retina

    Functional consequences of pre- and postsynaptic expression of synaptic plasticity

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    Growing experimental evidence shows that both homeostatic and Hebbian synaptic plasticity can be expressed presynaptically as well as postsynaptically. In this review, we start by discussing this evidence and methods used to determine expression loci. Next, we discuss functional consequences of this diversity in pre- and postsynaptic expression of both homeostatic and Hebbian synaptic plasticity. In particular, we explore the functional consequences of a biologically tuned model of pre- and postsynaptically expressed spike-timing-dependent plasticity complemented with postsynaptic homeostatic control. The pre- and postsynaptic expression in this model predicts 1) more reliable receptive fields and sensory perception, 2) rapid recovery of forgotten information (memory savings) and 3) reduced response latencies, compared to a model with postsynaptic expression only. Finally we discuss open questions that will require a considerable research effort to better elucidate how the specific locus of expression of homeostatic and Hebbian plasticity alters synaptic and network computations

    Short Term Synaptic Depression Imposes a Frequency Dependent Filter on Synaptic Information Transfer

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    Depletion of synaptic neurotransmitter vesicles induces a form of short term depression in synapses throughout the nervous system. This plasticity affects how synapses filter presynaptic spike trains. The filtering properties of short term depression are often studied using a deterministic synapse model that predicts the mean synaptic response to a presynaptic spike train, but ignores variability introduced by the probabilistic nature of vesicle release and stochasticity in synaptic recovery time. We show that this additional variability has important consequences for the synaptic filtering of presynaptic information. In particular, a synapse model with stochastic vesicle dynamics suppresses information encoded at lower frequencies more than information encoded at higher frequencies, while a model that ignores this stochasticity transfers information encoded at any frequency equally well. This distinction between the two models persists even when large numbers of synaptic contacts are considered. Our study provides strong evidence that the stochastic nature neurotransmitter vesicle dynamics must be considered when analyzing the information flow across a synapse

    Enduring Medial Perforant Path Short-Term Synaptic Depression at High Pressure

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    The high pressure neurological syndrome develops during deep-diving (>1.1 MPa) involving impairment of cognitive functions, alteration of synaptic transmission and increased excitability in cortico-hippocampal areas. The medial perforant path (MPP), connecting entorhinal cortex with the hippocampal formation, displays synaptic frequency-dependent-depression (FDD) under normal conditions. Synaptic FDD is essential for specific functions of various neuronal networks. We used rat cortico-hippocampal slices and computer simulations for studying the effects of pressure and its interaction with extracellular Ca2+ ([Ca2+]o) on FDD at the MPP synapses. At atmospheric pressure, high [Ca2+]o (4–6 mM) saturated single MPP field EPSP (fEPSP) and increased FDD in response to short trains at 50 Hz. High pressure (HP; 10.1 MPa) depressed single fEPSPs by 50%. Increasing [Ca2+]o to 4 mM at HP saturated synaptic response at a subnormal level (only 20% recovery of single fEPSPs), but generated a FDD similar to atmospheric pressure. Mathematical model analysis of the fractions of synaptic resources used by each fEPSP during trains (normalized to their maximum) and the total fraction utilized within a train indicate that HP depresses synaptic activity also by reducing synaptic resources. This data suggest that MPP synapses may be modulated, in addition to depression of single events, by reduction of synaptic resources and then may have the ability to conserve their dynamic properties under different conditions
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