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      Temporal Characteristics of Gustatory Responses in Rat Parabrachial Neurons Vary by Stimulus and Chemosensitive Neuron Type

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          Abstract

          It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of “sweet” (sucrose), “salty” (NaCl), “sour” (citric acid), and “bitter” (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs.

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          Bursts as a unit of neural information: making unreliable synapses reliable.

          J E Lisman (1997)
          Several lines of evidence indicate that brief (< 25 ms) bursts of high-frequency firing have special importance in brain function. Recent work shows that many central synapses are surprisingly unreliable at signaling the arrival of single presynaptic action potentials to the postsynaptic neuron. However, bursts are reliably signaled because transmitter release is facilitated. Thus, these synapses can be viewed as filters that transmit bursts, but filter out single spikes. Bursts appear to have a special role in synaptic plasticity and information processing. In the hippocampus, a single burst can produce long-term synaptic modifications. In brain structures whose computational role is known, action potentials that arrive in bursts provide more-precise information than action potentials that arrive singly. These results, and the requirement for multiple inputs to fire a cell suggest that the best stimulus for exciting a cell (that is, a neural code) is coincident bursts.
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            The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs.

            How random is the discharge pattern of cortical neurons? We examined recordings from primary visual cortex (V1; Knierim and Van Essen, 1992) and extrastriate cortex (MT; Newsome et al., 1989a) of awake, behaving macaque monkey and compared them to analytical predictions. For nonbursting cells firing at sustained rates up to 300 Hz, we evaluated two indices of firing variability: the ratio of the variance to the mean for the number of action potentials evoked by a constant stimulus, and the rate-normalized coefficient of variation (Cv) of the interspike interval distribution. Firing in virtually all V1 and MT neurons was nearly consistent with a completely random process (e.g., Cv approximately 1). We tried to model this high variability by small, independent, and random EPSPs converging onto a leaky integrate-and-fire neuron (Knight, 1972). Both this and related models predicted very low firing variability (Cv < 1) for realistic EPSP depolarizations and membrane time constants. We also simulated a biophysically very detailed compartmental model of an anatomically reconstructed and physiologically characterized layer V cat pyramidal cell (Douglas et al., 1991) with passive dendrites and active soma. If independent, excitatory synaptic input fired the model cell at the high rates observed in monkey, the Cv and the variability in the number of spikes were both very low, in agreement with the integrate-and-fire models but in strong disagreement with the majority of our monkey data. The simulated cell only produced highly variable firing when Hodgkin-Huxley-like currents (INa and very strong IDR) were placed on distal dendrites. Now the simulated neuron acted more as a millisecond-resolution detector of dendritic spike coincidences than as a temporal integrator. We argue that neurons that act as temporal integrators over many synaptic inputs must fire very regularly. Only in the presence of either fast and strong dendritic nonlinearities or strong synchronization among individual synaptic events will the degree of predicted variability approach that of real cortical neurons.
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              Nature and precision of temporal coding in visual cortex: a metric-space analysis.

              1. We recorded single-unit and multi-unit activity in response to transient presentation of texture and grating patterns at 25 sites within the parafoveal representation of V1, V2, and V3 of two awake monkeys trained to perform a fixation task. In grating experiments, stimuli varied in orientation, spatial frequency, or both. In texture experiments, stimuli varied in contrast, check size, texture type, or pairs of these attributes. 2. To examine the nature and precision of temporal coding, we compared individual responses elicited by each set of stimuli in terms of two families of metrics. One family of metrics, D(spike), was sensitive to the absolute spike time (following stimulus onset). The second family of metrics, D(interval), was sensitive to the pattern of interspike intervals. In each family, the metrics depend on a parameter q, which expresses the precision of temporal coding. For q = 0, both metrics collapse into the "spike count" metric D(Count), which is sensitive to the number of impulses but insensitive to their position in time. 3. Each of these metrics, with values of q ranging from 0 to 512/s, was used to calculate the distance between all pairs of spike trains within each dataset. The extent of stimulus-specific clustering manifest in these pairwise distances was quantified by an information measure. Chance clustering was estimated by applying the same procedure to synthetic data sets in which responses were assigned randomly to the input stimuli. 4. Of the 352 data sets, 170 showed evidence of tuning via the spike count (q = 0) metric, 294 showed evidence of tuning via the spike time metric, 272 showed evidence of tuning via the spike interval metric to the stimulus attribute (contrast, check size, orientation, spatial frequency, or texture type) under study. Across the entire dataset, the information not attributable to chance clustering averaged 0.042 bits for the spike count metric, 0.171 bits for the optimal spike time metric, and 0.107 bits for the optimal spike interval metric. 5. The reciprocal of the optimal cost q serves as a measure of the temporal precision of temporal coding. In V1 and V2, with both metrics, temporal precision was highest for contrast (ca. 10-30 ms) and lowest for texture type (ca. 100 ms). This systematic dependence of q on stimulus attribute provides a possible mechanism for the simultaneous representation of multiple stimulus attributes in one spike train. 6. Our findings are inconsistent with Poisson models of spike trains. Synthetic data sets in which firing rate was governed by a time-dependent Poisson process matched to the observed poststimulus time histogram (PSTH) overestimated clustering induced by D(count) and, for low values of q, D(spike)[q] and D(intervals)[q]. Synthetic data sets constructed from a modified Poisson process, which preserved not only the PSTH but also spike count statistics accounted for the clustering induced by D(count) but underestimated the clustering induced by D(spike)[q] and D(interval)[q].
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                4 October 2013
                : 8
                : 10
                : e76828
                Affiliations
                [1]Division of Oral Biology, College of Dentistry, the Ohio State University, Columbus, Ohio, United States of America
                University of Tokyo, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LG ST. Performed the experiments: LG. Analyzed the data: LG ST. Wrote the manuscript: LG ST.

                Article
                PONE-D-12-32540
                10.1371/journal.pone.0076828
                3790754
                24124597
                b49fd1cf-eab3-492f-93d1-a4b836a0f4c4
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 October 2012
                : 1 September 2013
                Funding
                The study was supported by NIH RO1-DC726315 (SPT) and RO3-DC008678 (LG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Research Article

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