Wide-band information transmission at the calyx of Held

We use a mathematical model of the calyx of Held to explore information transmission at this giant glutamatergic synapse. The significant depression of the postsynaptic response to repeated stimulation in vitro is a result of various activity-dependent processes in multiple time scales, which can be reproduced by multiexponential functions in this model. When stimulated by Poisson-distributed spike trains the amplitude of the postsynaptic current varies considerably with the preceding interspike intervals. Here we quantify the information contained in the postsynaptic current amplitude about preceding interspike intervals and determine the impact of different pre- and postsynaptic factors on information transmission. The mutual information between presynaptic spike times and the amplitude of the postsynaptic response in general decreases as the mean stimulation rate increases, but remains high even at frequencies greater than 100 Hz, unlike at many neocortical synapses. The maintenance of information transmission is attributable largely to vesicle recycling rates at low frequencies of stimulation, shifting to vesicle release probability at high frequencies. Also at higher frequencies the synapse operates largely in a release ready mode in which most release sites contain a release-ready vesicle and release probabilities are low

Theoretical models of synaptic short term plasticity

Short term plasticity is a highly abundant form of rapid, activity-dependent modulation of synaptic efficacy. A shared set of mechanisms can cause both depression and enhancement of the postsynaptic response at different synapses, with important consequences for information processing. Mathematical models have been extensively used to study the mechanisms and roles of short term plasticity. This review provides an overview of existing models and their biological basis, and of their main properties. Special attention will be given to slow processes such as calcium channel inactivation and the effect of activation of presynaptic autoreceptors

Processing Submillisecond Timing Differences in a Model Electrosensory System

Perception of sensory cues requires peripheral encoding followed by extraction of behaviorally relevant signal components by central neurons. Some sensory systems can detect temporal information with submillisecond accuracy, despite these signals occurring faster than the approximately 1 ms timescale of neuronal firing. In sound localization, the best studied example of this phenomenon, there are at least two distinct mechanisms for detecting submillisecond timing differences, indicating that multiple solutions to this fundamental problem exist. I investigated mechanisms for processing submillisecond timing differences by studying electrosensory processing in a time coding expert, mormyrid weakly electric fish, which can detect submillisecond differences in the duration of electric signals. First, I measured responses of peripheral receptors to stimuli of different durations. I found that each unit responded preferentially to longer stimuli, but with response thresholds that varied among units within the behaviorally relevant range of durations. This variability establishes a population code operating at near threshold intensities in which the number and identity of responding receptors represents duration. At higher stimulus intensities all units respond independent of duration, rendering the population code obsolete. Importantly, peripheral receptors respond either to the start or end of a signal. Thus, stimulus duration is also represented by a temporal code, as a difference in spike times between receptors. Next, I investigated the central mechanism for detection of submillisecond spike time differences by recording from time comparator neurons (Small Cells) in the midbrain. Recording from Small Cells is challenging because their somas are small and relatively inaccessible. I therefore designed a novel method using retrograde labeling to directly visualize and record from Small Cells in vivo. I showed that patterns of duration tuning vary among Small Cells due to a combination of blanking inhibition corresponding to one edge of a stimulus and variably delayed excitation corresponding to one or both edges of a stimulus. Other circuits that detect submillisecond timing differences rely either on precisely-timed inhibition or delay-line coincidence detection. I demonstrate a novel mechanism by which mormyrids combine delay-line coincidence detection with precisely-timed blanking inhibition to establish diverse patterns of duration tuning among a population of time comparators

Role of Inhibition in Binaural Processing

The medial and lateral superior olives (MSO, LSO) are the lowest order cell groups in the mammalian auditory circuit to receive massive binaural input. The MSO functions in part to encode interaural time differences (ITD), the predominant cue for localization of low frequency sounds. Binaural inputs to the MSO consist of excitatory projections from the cochlear nuclei (CN) and inhibitory projections from both the medial nucleus of the trapezoid body (MNTB) and lateral nucleus of the trapezoid body (LNTB). The interaction of excitatory and inhibitory currents within an MSO cell\u27s soma and dendrites over the backdrop of its intrinsic ionic conductances imbues ITD sensitivity to these neurons. Lloyd Jeffress proposed a coincidence detection circuit in which arrays of neurons receive sub-threshold excitatory inputs via delay lines that represent sound location as a place code of activity patterns within the cell group (Jeffress, 1948). The Jeffress place code model later found a neural instantiation in the MSO. Recent in vivo (McAlpine et al., 2001; Brand et al., 2002) studies have shown that peak discharge rates do not fall within the ecological range as the Jeffress model predicts but instead ITD is coded by changes in discharge rate. The timing of inhibition relative to excitation modulates the discharge rates of MSO cells (Brand et al., 2002; Chirila et al., 2007); however, the details of this circuit, such as the onset time of inhibition, are not well known. Although the MNTB and LNTB have been investigated in vivo and in vitro , they have not been well characterized with respect to their function in ITD processing in larger mammals. Additionally, inhibition is modulated by anesthesia and confounds in vivo experiments that examine the careful interplay of excitatory and inhibitory effects in the MSO. For this reason, these physiological experiments were performed on decerebrate unanaesthetized animals. Further investigation of the anatomical organization of inhibitory inputs was carried out as the basis for a comprehensive model of the MSO that incorporates the effects of binaural inhibiting projections to MSO neurons.;Unbiased stereological counts of the MNTB, MSO and subdivisions of the LNTB showed that the MSO and MNTB contain approximately the same number of cells. The main (m)LNTB, posteroventral (pv)LNTB and the hilus (h)LNTB are estimated to contain 3800, 1400, and 200 neurons respectively. Tonotopic organization of the MNTB and MSO show that in the low frequency area, MSO cells outnumber MNTB cells 2 to 1, suggesting a divergent innervation of the MSO from the MNTB. Injection of the retrograde tracer, biotinylated dextrane amine, in the MSO, labeled cells in the MNTB, pvLNTB and mLNTB and defines the important role that these sub-nuclei, and in particular the pvLNTB, have in ITD coding. Computational modeling of a single MSO cell suggests that when two sources of inhibition temporally frame excitation the coincidence detection window is refined and less sensitive to temporal fluctuations that otherwise might degrade ITD sensitivity. Finally, physiological properties of MNTB cells reveal a heterogeneous population of responses and less precise temporal coding than are found in their inputs, globular bushy cells

Characterization of the neocortical network excitability with multielectrode arrays: alterations in migraine and epilepsy mouse models.

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