756 research outputs found

    Hidden Terminal-Aware Contention Resolution with an Optimal Distribution

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    Achieving low-power operation in wireless sensor networks with high data load or bursty traffic is challenging. The hidden terminal problem is aggravated with increased amounts of data in which traditional backoff-based contention resolution mechanisms fail or induce high latency and energy costs. We analyze and optimize Strawman, a receiver-initiated contention resolution mechanism that copes with hidden terminals. We propose new techniques to boost the performance of Strawman while keeping the resolution overhead small. We finally validate our improved mechanism via experiments

    Functional roles of synaptic inhibition in auditory temporal processing

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    Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

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    During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregu- lated at high AP frequencies to balance SV consumption. We show that Munc13-1—an essential SV priming protein—regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotrans- mission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

    Information Processing at the Calyx of Held Synapse Under Natural Conditions

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    This study investigates the role of the medial nucleus of the trapezoid body (MNTB) in sound processing. The experimental part focuses on in vitro experiments in acute brain slices of Mongolian gerbils, in parallel a theoretical approach explains the experimental results in the context of a mathematical vesicle-release model. One of the hallmarks of auditory neurons in vivo is spontaneous activity that occurs even in the absence of any sensory stimuli. Sound evoked bursts of discharges are thus embedded within this background of random firing. The calyx of Held synapse has been characterized in vitro as a fast relay that reliably fires at high stimulus frequencies (up to 800 Hz). However, inherently due to the preparation method, spontaneous activity is absent in studies using brain slices. This study deals with the question how this ongoing activity is influencing synaptic transmission. The answer is divided into three parts. In the first part a phenomenological description of the effects of spontaneous activity on synaptic transmission is given. Therefore in vivo spontaneous firing rates were determined and then reintroduced as random firing patterns to in vitro brain stem synapses. After conditioning synapses for two minutes at Poisson averaged rates of 20, 40, and 60 Hz, a number of differences in synaptic transmission were observed. Accordingly, current-clamp, dynamic-clamp, and loose-patch recordings revealed a number of failures at the postsynaptic cell, although the initial onset of evoked activity was still transmitted with higher fidelity. The conclusion of these observations is that in vivo auditory synapses are in a tonic state of reduced EPSCs as a consequence of spontaneous spiking. In the second part the conditioned state of calyx of Held synapse is closer investigated by modeling the short-term dynamics with a biophysically motivated vesicle release model. The mechanisms regulating short-term plasticity can be demonstrated in physiological studies as well as computer models aimed at testing the functional role of them. In the case of the calyx of Held synapse, considerable progress has been made in understanding the dynamics of transmission both on a physiological and modeling level. Nevertheless, little is known about the processing of complex, long lasting stimulation patterns mimicking the input typically present in the intact brain. Furthermore, calyx of Held synapses are chronically active in vivo due to spontaneous activity in the auditory brainstem. Here we test synaptic responses to complex stimulation protocols mimicking periods of low and high activity, as well as protocols derived from natural sound clips. Additionally, all stimuli were embedded in chronic background activity attempting to imitate the naturally occurring spontaneous activity. We measured synaptic responses to these stimulus trains and then used the data to test how well several vesicle-release models could capture the dynamics observed physiologically. Already the most basic model variant produced very good results with correlation coefficients between the experimental data and the model prediction of more than 90%. None of the more complex model variants, which incorporated additional physiological effects, could improve this prediction accuracy significantly. The conclusion of these results is that the functional state of chronically active calyces differs from the functional state of silent calyces, and that this chronically active functional state can be described in simpler terms. Finally the third part focuses on the transition phase between completely rested synapses and synapses conditioned with simulated spontaneous activity. Modeling the transition phase at the beginning of the conditioning period reveals significant changes in the model parameters thus suggesting changes in the underlying biophysical parameters including the vesicle pool size and the release probability. Recovery experiments after switching off the spontaneous activity confirm the reduced pool size and show a very slow recovery on a time scale of minutes. This slow recovery is accompanied by a reduction in the frequency of miniature EPSCs, a measure for the concentration of calcium ions in the presynaptic terminal. The observed changes again confirm the finding that synapses under the influence of ongoing activity show different properties than completely rested synapses. Overall the results of this study show that spontaneous activity has significant influences on the synaptic dynamics of cells in the MNTB. The point of view that the calyx of Held is not just a relay station transforming excitatory input into inhibitory output is further strengthened, and this has consequences for the encoding of signals throughout the auditory pathway

    Polarity and Competition in the Development of the Calyx of Held Terminal in the Medial Nucleus of the Trapezoid Body in the Mouse

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    In the auditory brainstem, the connection between globular bushy cells of the anteroventral cochlear nucleus and principal cells (PCs) of the medial nucleus of the trapezoid body (MNTB) is created by one of the largest nerve terminals in the central nervous system, the calyx of Held (CH). The characteristics of the CH:MNTB connection—a short developmental period (48-72 hours), accessibility for recording from pre- and postsynaptic components, and clear monoinnervated end point—make this system an ideal model system for studying nervous system development. Model systems undergo stereotyped stages of development, including exuberant overinnervation, competition between terminals, and a refinement of innervation through removal of weak inputs. However, unlike other similar model systems (climbing fiber:Purkinje cell, retinal ganglion cells:dorsolateral geniculate nucleus), it has been a long-standing question whether the CH:MNTB system undergoes competition. We investigated the innervation state of PCs using the novel technique of segmentation and 3D reconstruction of PCs and their associated inputs across important developmental timepoints (postnatal days (P)2,3,4,6,9,30). This was accomplished by application of serial block-face scanning electron microscopy (SBEM), a method of serial section electron microscopy providing high spatial resolution (~4-10nm) and a high degree of alignment between images with very little section loss. Applying this technique, we show early exuberant innervation of PCs (P2), establish that competition is a common process, and pinpoint the 24-hour period from P3-P4 as a uniquely active day in CH growth during which terminal contact with PCs increases at a rate exceeding 200 µm2/day. Common morphological characteristics of the CH:MNTB connection also became qualitatively evident based on 3D reconstructions, particularly an eccentric PC nucleus and preference for polarized terminal growth. Based on these observations, we undertook a quantitative study of polarity in CH:MNTB development using our 3D reconstructions. The results of this investigation demonstrate a novel polarity in development of both the CH and PC; developing PCs are characterized by eccentrically placed nuclei that establish an “intrasomatic polarity” that persists through young adulthood (P30). This polarity appears to define a unique territory opposite of the nuclear location that is amenable to growth of the calyx, is enriched in dendrites, and is selectively enlarged as the principal cell matures to create glia-free surface area for innervation. To our knowledge, this is the first report of a polarity program in the coordinated pre- and postsynaptic development of a non-laminar brain region. Additionally, our findings have codified a progression of dendritic pruning in the maturation of principal cells that may influence and be influenced by the developmental state of the cell. Taken in totality, these results indicate a highly polarized, systemic competitive process in the MNTB during the development of the calyx of Held and suggests potential mediators of competition that deserve further study

    Modifications of gustatory nerve synapses onto nucleus of the solitary tract neurons induced by dietary sodium-restriction during development

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    The terminal fields of nerves carrying gustatory information to the rat brainstem show a remarkable amount of expansion in the nucleus of the solitary tract (NTS) as a result of early dietary sodium restriction. However, the extent to which these axonal changes represent corresponding changes in synapses is not known. To identify the synaptic characteristics that accompany the terminal field expansion, the greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal (IX) nerves were labeled in rats fed a sodium-restricted diet during pre- and postnatal development. The morphology of these nerve terminals within the NTS region where the terminal fields of all three nerves overlap was evaluated by transmission electron microscopy. Compared to data from control rats, CT axons were the most profoundly affected. The density of CT arbors and synapses quadrupled as a result of the near life-long dietary manipulation. In contrast, axon and synapse densities of GSP and IX nerves were not modified in sodium-restricted rats. Furthermore, compared to controls, CT terminals displayed more instances of contacts with postsynaptic dendritic protrusions and IX terminals synapsed more frequently with dendritic shafts. Thus, dietary sodium restriction throughout pre- and postnatal development had differential effects on the synaptic organization of the three nerves in the NTS. These anatomical changes may underlie the impact of sensory restriction during development on the functional processing of taste information and taste-related behaviors. J. Comp. Neurol. 508:529–541, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58547/1/21708_ftp.pd

    Cervical Vertebral Maturation Stage as a Growth Predictor

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    The purposes of this study were to establish the reproducibility of skeletal age assessment as determined by the stage of cervical vertebral maturation (CVM) and to assess the ability of the CVM method to predict timing of peak mandibular growth velocity (PMdGV). The longitudinal records of 104 females (age 8 to 14 inclusive) were used to determine skeletal age (as assessed by the CVM) and mandibular length. Reproducibility of skeletal age estimates was tested by comparing five sets of first and second determinations done 2 months apart for 20 subjects chosen from the total sample before and after the principal operator calibration. The reproducibility of skeletal age assessments done prior to calibration was unacceptable. The reproducibility improved to acceptable limits following calibration. Improved definitions, the addition of an extra stage and the development of a Sequential Conditional Flow Chart rendered the modified CVM method, introduced in this study, even more reproducible. The kappa for 20 double assessments of the timing of PMdGV was 59% (not acceptable) but of the 55 subjects for whom two determinations of timing of PMdGV coincided, only 61% were at cervical vertebral stage 3 thus lending some measure of uncertainty to the use of the cervical vertebral maturation method for predicting timing of PMdGV

    Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

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    During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregulated at high AP frequencies to balance SV consumption. We show that Munc13-1-an essential SV priming protein-regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotransmission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

    Network connectivity probability analysis based on its states inversion

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    Представлен вариант устранения основного недостатка наиболее совершенных модификаций метода, использующих многопеременную инверсию. Он предполагает рассмотрение не объединения событий связности (несвязности), вырождающегося в сумму несовместных произведений, а пересечения противоположных событий. Подобная сумма не требует использования многопеременной инверсии для каждого из слагаемых. В итоге данные преобразования позволяют анализировать вероятность связности произвольного графа с несколько меньшей вычислительной сложностью по сравнению с классическими методами многопеременной инверсии
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