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    AuthorTitleYearJournal/ProceedingsReftypeDOI/URL
    Delescluse, M., Franconville, R., Joucla, S., Lieury, T. & Pouzat, C. Making neurophysiological data analysis reproducible. Why and how? 2011 Journal of Physiology (Paris)
    Vol. in press 
    article URL 
    Abstract: Reproducible data analysis is an approach aiming at complementing classical printed scientific articles with everything required to independently reproduce the results they present. ''Everything'' covers here: the data, the computer codes and a precise description of how the code was applied to the data. A brief history of this approach is presented first, starting with what economists have been calling replication since the early eighties to end with what is now called reproducible research in computational data analysis oriented fields like statistics and signal processing. Since efficient tools are instrumental for a routine implementation of these approaches, a description of some of the available ones is presented next. A toy example demonstrates then the use of two open source software for reproducible data analysis: the ''Sweave family'' and the org-mode of emacs. The former is bound to R while the latter can be used with R, Matlab, Python and many more ''generalist'' data processing software. Both solutions can be used with Unix-like, Windows and Mac families of operating systems. It is argued that neuroscientists could communicate much more efficiently their results by adopting the reproducible research paradigm from their lab books all the way to their articles, thesis and books
    BibTeX:
    @article{Delescluse+:2011b,
      author = {Matthieu Delescluse and Romain Franconville and Sébastien Joucla and Tiffany Lieury and Christophe Pouzat},
      title = {Making neurophysiological data analysis reproducible. Why and how?},
      journal = {Journal of Physiology (Paris)},
      year = {2011},
      volume = {in press},
      url = {http://hal.archives-ouvertes.fr/hal-00591455/fr/}
    }
    
    Einvoll, G., Franke, F., Pouzat, E.H.C. & Harris, K.D. Towards reliable spike-train recordings from thousands of neurons with multielectrodes 2011 Current Opinions in Neurobiology
    Vol. in press 
    article  
    BibTeX:
    @article{Einvoll+:2011,
      author = {Gaute Einvoll and Felix Franke and Espen Hagenand Christophe Pouzat and Kenneth D Harris},
      title = {Towards reliable spike-train recordings from thousands of neurons with multielectrodes},
      journal = {Current Opinions in Neurobiology},
      year = {2011},
      volume = {in press}
    }
    
    Joucla, S., Pippow, A., Kloppenburg, P. & Pouzat, C. Quantitative estimation of calcium dynamics from ratiometric measurements: A direct, non-ratioing, method. 2010 Journal of Neurophysiology
    Vol. 103, pp. 1130-1144 
    article DOI URL 
    Abstract: Measuring variations of intracellular free calcium concentration through the changes in fluorescence of a calcium sensitive dye is a ubiquitous technique in neuroscience. Despite its popularity, confidence intervals (CIs) on the estimated parameters of calcium dynamics models are seldom given. To address this issue, we have developed a 2-stage model for ratiometric measurements obtained with a CCD camera. Its first element embeds a parametric calcium dynamics model into a fluorescence intensity model, and its second element describes probabilistically the fluorescence measurements by a CCD camera. Using Monte-Carlo simulations, we first show that the classical ratiometric transformation gives reliable CIs for time constants only, and not baseline calcium concentration nor influx. We then introduce a direct method, which consists of fitting directly and simultaneously the fluorescence transients at both wavelengths, without any data ratioing. This approach uses a probabilistic description of the camera, leading to the construction of meaningful CIs for the calcium parameters. Moreover, using approaches inspired by constrained linear regression, we can take into account the finite precision on calibrated parameters (such as the dye dissociation constant in the cell). These key features are illustrated on simulated data using Monte-Carlo simulations. We illustrate moreover the strength of the direct method on experimental recordings from insect olfactory interneurons. In particular, we show how to handle a time-dependent buffer concentration, thereby considerably improving our goodness of fit. The direct method was implemented in the open-source software R and is freely distributed in the CalciOMatic package.
    BibTeX:
    @article{JouclaEtAl_2010,
      author = {Sebastien Joucla and Andreas Pippow and Peter Kloppenburg and Christophe Pouzat},
      title = {Quantitative estimation of calcium dynamics from ratiometric measurements: A direct, non-ratioing, method.},
      journal = {Journal of Neurophysiology},
      year = {2010},
      volume = {103},
      pages = {1130--1144},
      url = {http://intl-jn.physiology.org/cgi/content/short/103/2/1130},
      doi = {http://dx.doi.org/10.1152/jn.00414.2009}
    }
    
    Tiganj, Z., Mboup, M., Pouzat, C. & Belkoura, L. An Algebraic Method for Eye Blink Artifacts Detection in Single Channel EEG Recordings 2010
    Vol. 28IFMBE Proceedings. 17th International Conference on Advances in Biomagnetism (Biomag2010), pp. 175-178 
    inproceedings  
    BibTeX:
    @inproceedings{Tiganj2010,
      author = {Z. Tiganj and M. Mboup and C. Pouzat and L. Belkoura},
      title = {An Algebraic Method for Eye Blink Artifacts Detection in Single Channel EEG Recordings},
      booktitle = {IFMBE Proceedings. 17th International Conference on Advances in Biomagnetism (Biomag2010)},
      year = {2010},
      volume = {28},
      pages = {175-178}
    }
    
    Pippow, A., Husch, A., Pouzat, C. & Kloppenburg, P. Differences of Ca(2+) handling properties in identified central olfactory neurons of the antennal lobe. 2009 Cell Calcium
    Vol. 46(2), pp. 87-98 
    article DOI URL 
    Abstract: Information processing in neurons depends on highly localized Ca(2+) signals. The spatial and temporal dynamics of these signals are determined by a variety of cellular parameters including the calcium influx, calcium buffering and calcium extrusion. Our long-term goal is to better understand how intracellular Ca(2+) dynamics are controlled and contribute to information processing in defined interneurons of the insect olfactory system. The latter has served as an excellent model to study general mechanisms of olfaction. Using patch-clamp recordings and fast optical imaging in combination with the 'added buffer approach', we analyzed the Ca(2+) handling properties of different identified neuron types in Periplaneta americana's olfactory system. Our focus was on two types of local interneurons (LNs) with significant differences in intrinsic electrophysiological properties: (1) spiking LNs that generate 'normal' Na(+) driven action potentials and (2) non-spiking LNs that do not express voltage-activated Na(+) channels. We found that the distinct electrophysiological properties from different types of central olfactory interneurons are strongly correlated with their cell specific calcium handling properties: non-spiking LNs, in which Ca(2+) is the only cation that enters the cell to contribute to membrane depolarization, had the highest endogenous Ca(2+) binding ratio and Ca(2+) extrusion rate.
    BibTeX:
    @article{PippowEtAl_2009,
      author = {Andreas Pippow and Andreas Husch and Christophe Pouzat and Peter Kloppenburg},
      title = {Differences of Ca(2+) handling properties in identified central olfactory neurons of the antennal lobe.},
      journal = {Cell Calcium},
      year = {2009},
      volume = {46},
      number = {2},
      pages = {87-98},
      url = {http://dx.doi.org/10.1016/j.ceca.2009.05.004},
      doi = {http://dx.doi.org/10.1016/j.ceca.2009.05.004}
    }
    
    Pouzat, C. & Chaffiol, A. Automatic Spike Train Analysis and Report Generation. An Implementation with R, R2HTML and STAR 2009 J Neurosci Methods
    Vol. 181, pp. 119-144 
    article URL 
    BibTeX:
    @article{PouzatChaffiol_2009,
      author = {Christophe Pouzat and Antoine Chaffiol},
      title = {Automatic Spike Train Analysis and Report Generation. An Implementation with R, R2HTML and STAR},
      journal = {J Neurosci Methods},
      year = {2009},
      volume = {181},
      pages = {119--144},
      note = {Pre-print available at: http://sites.google.com/site/spiketrainanalysiswithr/Home/PouzatChaffiol_JNM_2009.pdf?attredirects=0},
      url = {http://sites.google.com/site/spiketrainanalysiswithr/}
    }
    
    Pouzat, C. & Chaffiol, A. On Goodness of Fit Tests For Models of Neuronal Spike Trains Considered as Counting Processes 2009   misc URL 
    Abstract: After an elementary derivation of the "time transformation", mapping a counting process onto a homogeneous Poisson process with rate one, a brief review of Ogata's goodness of fit tests is presented and a new test, the "Wiener process test", is proposed. This test is based on a straightforward application of Donsker's Theorem to the intervals of time transformed counting processes. The finite sample properties of the test are studied by Monte Carlo simulations. Performances on simulated as well as on real data are presented. It is argued that due to its good finite sample properties, the new test is both a simple and a useful complement to Ogata's tests. Warnings are moreover given against the use of a single goodness of fit test.
    BibTeX:
    @misc{PouzatChaffiol_2009b,
      author = {Christophe Pouzat and Antoine Chaffiol},
      title = {On Goodness of Fit Tests For Models of Neuronal Spike Trains Considered as Counting Processes},
      year = {2009},
      url = {http://arxiv.org/abs/0909.2785}
    }
    
    Escola, R., Pouzat, C., Chaffiol, A., Yvert, B., Magnin, I.E. & Guillemaud, R. SIMONE : A Neural Simulator to Test MEA-embedded Algorithms. 2008 IEEE Transactions on Neural and Rehabilitation Engineering
    Vol. 16(2), pp. 149-160 
    article DOI  
    Abstract: Contemporary multielectrode arrays (MEAs) used to record extracellular activity from neural tissues can deliver data at rates on the order of 100 Mbps. Such rates require efficient data compression and/or preprocessing algorithms implemented on an application specific integrated circuit (ASIC) close to the MEA. We present SIMONE (Statistical sIMulation Of Neuronal networks Engine), a versatile simulation tool whose parameters can be either fixed or defined by a probability distribution. We validated our tool by simulating data recorded from the first olfactory relay of an insect. Different key aspects make this tool suitable for testing the robustness and accuracy of neural signal processing algorithms (such as the detection, alignment, and classification of spikes). For instance, most of the parameters can be defined by a probabilistic distribution, then tens of simulations may be obtained from the same scenario. This is especially useful when validating the robustness of the processing algorithm. Moreover, the number of active cells and the exact firing activity of each one of them is perfectly known, which provides an easy way to test accuracy.
    BibTeX:
    @article{EscolaEtAl_2008,
      author = {Escola, Ricardo and Pouzat, Christophe and Chaffiol, Antoine and Yvert, Blaise and Magnin, Isabelle E. and Guillemaud, Regis},
      title = {SIMONE : A Neural Simulator to Test MEA-embedded Algorithms.},
      journal = {IEEE Transactions on Neural and Rehabilitation Engineering},
      year = {2008},
      volume = {16},
      number = {2},
      pages = {149--160},
      doi = {http://dx.doi.org/10.1109/TNSRE.2007.914467}
    }
    
    Mejia-Gervacio, S., Collin, T., Pouzat, C., Tan, Y.P., Llano, I. & Marty, A. Axonal Speeding: Shaping Synaptic Potentials in Small Neurons by the Axonal Membrane Compartment 2007 Neuron
    Vol. 53(6), pp. 843-855 
    article DOI  
    Abstract: The role of the axonal membrane compartment in synaptic integration is usually neglected. We show here that in interneurons of the cerebellar molecular layer, where dendrites are so short that the somatodendritic domain can be considered isopotential, the axonal membrane contributes a significant part of the cell input capacitance. We examine the impact of axonal membrane on synaptic integration by cutting the axon with two-photon illumination. We find that the axonal compartment acts as a sink for signals generated at fast conductance synapses, thus increasing the initial decay rate of corresponding synaptic potentials over the value predicted from the resistance-capacitance (RC) product of the cell membrane; signals generated at slower synapses are much less affected. This mechanism sharpens the spike firing precision of fast glutamatergic inputs without resorting to multisynaptic pathways.
    BibTeX:
    @article{MeijaEtAl_2007,
      author = {Mejia-Gervacio, Sheyla and Collin, Thibault and Pouzat, Christophe and Tan, Yusuf P. and Llano, Isabel and Marty, Alain},
      title = {Axonal Speeding: Shaping Synaptic Potentials in Small Neurons by the Axonal Membrane Compartment},
      journal = {Neuron},
      year = {2007},
      volume = {53},
      number = {6},
      pages = {843--855},
      doi = {http://dx.doi.org/10.1016/j.neuron.2007.02.023}
    }
    
    Testoni, N., Speciale, N., Ridolfi, A. & Pouzat, C. Adaptive wavelet-based signal dejittering 2007 Microelectronics and Electronics Conference, 2007. RME. Ph.D. Research in, pp. 257-260  inproceedings DOI  
    Abstract: Sampling is commonly retained as a critical step in any mixed-signal system. High-speed analog-to-digital converter sampling jitter limits all-over performance of these systems introducing a signal dependent noise in the sampled signal. In most environments it is desirable to reduce sampling clock jitter, however there are cases where designers are forced to introduce or cope with this undesirable noise effect. This work describes an innovative algorithm based on multiresolution analysis (MRA) which allows for the recovery of the original unjittered sampled signal in environments where clock jitter is unavoidable. We make use of a new versatile signal model and an MSE estimation in the Wavelet domain which lead to an adaptive Wavelet resealing technique centered around a fully precalculable resealing matrix. This technique has been successfully applied to other fields, like extracellular recording (ER) signal denoising, since it can be shown this problem can be reformulated into a signal dejittering problem.
    BibTeX:
    @inproceedings{TestoniEtAl_2007,
      author = {Testoni, Nicola and Speciale, Nicolo and Ridolfi, Andrea and Pouzat, Christophe},
      title = {Adaptive wavelet-based signal dejittering},
      booktitle = {Microelectronics and Electronics Conference, 2007. RME. Ph.D. Research in},
      year = {2007},
      pages = {257-260},
      doi = {http://dx.doi.org/10.1109/RME.2007.4401861}
    }
    
    Delescluse, M. & Pouzat, C. Efficient spike-sorting of multi-state neurons using inter-spike intervals information 2006 J Neurosci Methods
    Vol. 150(1), pp. 16-29 
    article DOI URL 
    Abstract: We demonstrate the efficacy of a new spike-sorting method based on a Markov Chain Monte Carlo (MCMC) algorithm by applying it to real data recorded from Purkinje cells (PCs) in young rat cerebellar slices. This algorithm is unique in its capability to estimate and make use of the firing statistics as well as the spike amplitude dynamics of the recorded neurons. PCs exhibit multiple discharge states, giving rise to multimodal interspike interval (ISI) histograms and to correlations between successive ISIs. The amplitude of the spikes generated by a PC in an "active" state decreases, a feature typical of many neurons from both vertebrates and invertebrates. These two features constitute a major and recurrent problem for all the presently available spike-sorting methods. We first show that a Hidden Markov Model with 3 log-Normal states provides a flexible and satisfying description of the complex firing of single PCs. We then incorporate this model into our previous MCMC based spike-sorting algorithm (Pouzat et al, 2004, J. Neurophys. 91, 2910-2928) and test this new algorithm on multi-unit recordings of bursting PCs. We show that our method successfully classifies the bursty spike trains fired by PCs by using an independent single unit recording from a patch-clamp pipette.
    BibTeX:
    @article{DelesclusePouzat_2005,
      author = {Delescluse, Matthieu and Pouzat, Christophe},
      title = {Efficient spike-sorting of multi-state neurons using inter-spike intervals information},
      journal = {J Neurosci Methods},
      year = {2006},
      volume = {150},
      number = {1},
      pages = {16--29},
      note = {Also available on the arXiv pre-print server: q-bio/0505053; http://arxiv.org/abs/q-bio/0505053},
      url = { http://arxiv.org/abs/q-bio/0505053 },
      doi = {http://dx.doi.org/10.1016/j.jneumeth.2005.05.023}
    }
    
    Pouzat, C. Methods and Models in Neurophysics. Les Houches 2003 Summer School. 2005 q-bio.QM/0405012, pp. 729-786  inbook URL 
    BibTeX:
    @inbook{Pouzat_2005,
      author = {Pouzat, Christophe},
      title = {Methods and Models in Neurophysics. Les Houches 2003 Summer School.},
      journal = {q-bio.QM/0405012},
      publisher = {Elsevier},
      year = {2005},
      pages = {729-786},
      note = {Available from: http://fr.arxiv.org/abs/q-bio.QM/0405012},
      url = {http://fr.arxiv.org/abs/q-bio.QM/0405012}
    }
    
    Pouzat, C., Delescluse, M., Viot, P. & Diebolt, J. Improved spike-sorting by modeling firing statistics and burst-dependent spike amplitude attenuation: a Markov chain Monte Carlo approach. 2004 J Neurophysiol
    Vol. 91(6), pp. 2910-2928 
    article DOI URL 
    Abstract: Spike-sorting techniques attempt to classify a series of noisy electrical waveforms according to the identity of the neurons that generated them. Existing techniques perform this classification ignoring several properties of actual neurons that can ultimately improve classification performance. In this study, we propose a more realistic spike train generation model. It incorporates both a description of "nontrivial" (i.e., non-Poisson) neuronal discharge statistics and a description of spike waveform dynamics (e.g., the events amplitude decays for short interspike intervals). We show that this spike train generation model is analogous to a one-dimensional Potts spin-glass model. We can therefore tailor to our particular case the computational methods that have been developed in fields where Potts models are extensively used, including statistical physics and image restoration. These methods are based on the construction of a Markov chain in the space of model parameters and spike train configurations, where a configuration is defined by specifying a neuron of origin for each spike. This Markov chain is built such that its unique stationary density is the posterior density of model parameters and configurations given the observed data. A Monte Carlo simulation of the Markov chain is then used to estimate the posterior density. We illustrate the way to build the transition matrix of the Markov chain with a simple, but realistic, model for data generation. We use simulated data to illustrate the performance of the method and to show that this approach can easily cope with neurons firing doublets of spikes and/or generating spikes with highly dynamic waveforms. The method cannot automatically find the "correct" number of neurons in the data. User input is required for this important problem and we illustrate how this can be done. We finally discuss further developments of the method.
    BibTeX:
    @article{PouzatEtAl_2004,
      author = {Pouzat, C. and Delescluse, M. and Viot, P. and Diebolt, J.},
      title = {Improved spike-sorting by modeling firing statistics and burst-dependent spike amplitude attenuation: a Markov chain Monte Carlo approach.},
      journal = {J Neurophysiol},
      year = {2004},
      volume = {91},
      number = {6},
      pages = {2910--2928},
      note = {Available from: http://intl-jn.physiology.org/cgi/content/abstract/91/6/2910},
      url = {http://intl-jn.physiology.org/cgi/content/abstract/91/6/2910},
      doi = {http://dx.doi.org/10.1152/jn.00227.2003}
    }
    
    Pouzat, C., Mazor, O. & Laurent, G. Using noise signature to optimize spike-sorting and to assess neuronal classification quality. 2002 J Neurosci Methods
    Vol. 122(1), pp. 43-57 
    article DOI  
    Abstract: We have developed a simple and expandable procedure for classification and validation of extracellular data based on a probabilistic model of data generation. This approach relies on an empirical characterization of the recording noise. We first use this noise characterization to optimize the clustering of recorded events into putative neurons. As a second step, we use the noise model again to assess the quality of each cluster by comparing the within-cluster variability to that of the noise. This second step can be performed independently of the clustering algorithm used, and it provides the user with quantitative as well as visual tests of the quality of the classification.
    BibTeX:
    @article{PouzatEtAl_2002,
      author = {Pouzat, C. and Mazor, O. and Laurent, G.},
      title = {Using noise signature to optimize spike-sorting and to assess neuronal classification quality.},
      journal = {J Neurosci Methods},
      year = {2002},
      volume = {122},
      number = {1},
      pages = {43--57},
      note = {Pre-print available at: http://www.biomedicale.univ-paris5.fr/physcerv/C_Pouzat/Papers_folder/PouzatEtAl_2002.pdf},
      doi = {http://dx.doi.org/10.1016/S0165-0270(02)00276-5}
    }
    
    Forti, L., Pouzat, C. & Llano, I. Action potential-evoked Ca2+ signals and calcium channels in axons of developing rat cerebellar interneurones. 2000 J Physiol
    Vol. 527 Pt 1, pp. 33-48 
    article URL 
    Abstract: Axonal [Ca2+] transients evoked by action potential (AP) propagation were studied by monitoring the fluorescence of the high-affinity calcium-sensitive dye Oregon Green 488 BAPTA-1, introduced through whole-cell recording pipettes in the molecular layer of interneurones from cerebellar slices of young rats. The spatiotemporal profile of Ca2+-dependent fluorescence changes was analysed in well-focused axonal stretches a few tens of micrometres long. AP-evoked Ca2+ signals were heterogeneously distributed along axons, with the largest and fastest responses appearing in hot spots on average approximately 5 microm apart. The spatial distribution of fluorescence responses was independent of the position of the focal plane, uncorrelated to basal dye fluorescence, and independent of dye concentration. Recordings using the low-affinity dye mag-fura-2 and a Cs+-based intracellular solution revealed a similar pattern of hot spots in response to depolarisation, ruling out measurement artefacts or possible effects of inhomogeneous dye distribution in the generation of hot spots. Fluorescence responses to a short train of APs in hot spots decreased by 41-76 % after bath perfusion of omega-conotoxin MVIIC (5-6 microM), and by 17-65 % after application of omega-agatoxin IVA (500 nM). omega-Conotoxin GVIA (1 microM) had a variable, small effect (0-31 % inhibition), and nimodipine (5 microM) had none. Somatically recorded voltage-gated currents during depolarising pulses were unaffected in all cases. These data indicate that P/Q-type Ca2+ channels, and to a lesser extent N-type channels, are responsible for a large fraction of the [Ca2+] rise in axonalhot spots. [Ca2+] responses never failed during low-frequency (<= 0.5 Hz) stimulation, indicating reliable AP propagation to the imaged sites. Axonal branching points coincided with a hot spot in approximately 50 % of the cases. The spacing of presynaptic varicosities, as determined by a morphological analysis of Neurobiotin-filled axons, was approximately 10 times larger than the one measured for hot spots. The latter is comparable to the spacing reported for varicosities in mature animals. We discuss the nature of hot spots, considering as the most parsimonious explanation that they represent functional clusters of voltage-dependent Ca2+ channels, and possibly other [Ca2+] sources, marking the position of developing presynaptic terminals before the formation of en passant varicosities.
    BibTeX:
    @article{FortiEtAl_2000,
      author = {Forti, L. and Pouzat, C. and Llano, I.},
      title = {Action potential-evoked Ca2+ signals and calcium channels in axons of developing rat cerebellar interneurones.},
      journal = {J Physiol},
      year = {2000},
      volume = {527 Pt 1},
      pages = {33-48},
      url = {http://jp.physoc.org/cgi/content/abstract/527/1/33}
    }
    
    Pouzat, C. & Marty, A. Somatic recording of GABAergic autoreceptor current in cerebellar stellate and basket cells. 1999 J Neurosci
    Vol. 19(5), pp. 1675-1690 
    article URL 
    Abstract: Patch-clamp recordings were performed from stellate and basket cells in rat cerebellar slices. Under somatic voltage clamp, short depolarizing pulses were applied to elicit action potentials in the axon. After the action potential, a bicuculline- and Cd2+-sensitive current transient was observed. A similar response was obtained when eliciting axonal firing by extracellular stimulation. With an isotonic internal Cl- solution, the peak amplitude of this current varied linearly with the holding potential, yielding an extrapolated reversal potential of -20 to 0 mV. Unlike synaptic or autaptic GABAergic currents obtained in the same preparation, the current transient had a slow rise-time and a low variability between trials. This current was blocked when 10 mM BAPTA was included in the recording solution. In some experiments, the current transient elicited axonal action potentials. The current transient was reliably observed in animals aged 12-15 d, with a mean amplitude of 82 pA at -70 mV, but was small and rare in the age group 29-49 d. Numerical simulations could account for all properties of the current transient by assuming that an action potential activates a distributed GABAergic conductance in the axon. The actual conductance is probably restricted to release sites, with an estimated mean presynaptic current response of 10 pA per site (-70 mV, age 12-15 d). We conclude that in developing rats, stellate and basket cell axons have a high density of GABAergic autoreceptors and that a sizable fraction of the corresponding current can be measured from the soma.
    BibTeX:
    @article{PouzatMarty_1999,
      author = {Pouzat, C. and Marty, A.},
      title = {Somatic recording of GABAergic autoreceptor current in cerebellar stellate and basket cells.},
      journal = {J Neurosci},
      year = {1999},
      volume = {19},
      number = {5},
      pages = {1675--1690},
      url = {http://www.jneurosci.org/cgi/content/abstract/19/5/1675}
    }
    
    Pouzat, C. & Marty, A. Autaptic inhibitory currents recorded from interneurones in rat cerebellar slices. 1998 J Physiol
    Vol. 509 ( Pt 3), pp. 777-783 
    article URL 
    Abstract: 1. While the presence of autapses in the brain is indicated by a large body of morphological evidence, the functional role of these structures has remained unclear. To probe for autaptic currents, we have recorded current responses following short somatic depolarizing pulses in Cl--loaded interneurones (stellate and basket cells) from rat cerebellar slices (animals aged 27-39 days). 2. In approximately 20 % of the recordings, fluctuating inward current transients were obtained with a latency of 1.15-2.45 ms (measured from the peak of the depolarization-induced Na+ current; n = 10). 3. These transients were blocked by bicuculline and were sensitive to the extracellular Ca2+ concentration. 4. Assuming low release probability, as suggested by the high failure rate (0.65-0.92, n = 10), quantal sizes ranging from 21 to 178 pA (-70 mV; n = 10) were calculated from a variance analysis of autaptic current amplitudes. 5. We conclude that approximately 20 % of interneurones have a functional autapse. Autaptic currents may inhibit firing of interneurones during high frequency discharges.
    BibTeX:
    @article{PouzatMarty_1998,
      author = {Pouzat, C. and Marty, A.},
      title = {Autaptic inhibitory currents recorded from interneurones in rat cerebellar slices.},
      journal = {J Physiol},
      year = {1998},
      volume = {509 ( Pt 3)},
      pages = {777--783},
      url = {http://jp.physoc.org/cgi/content/abstract/509/3/777}
    }
    
    Pouzat, C. & Hestrin, S. Developmental regulation of basket/stellate cell-->Purkinje cell synapses in the cerebellum. 1997 J Neurosci
    Vol. 17(23), pp. 9104-9112 
    article URL 
    Abstract: We used paired recordings to study the development of synaptic transmission between inhibitory interneurons of the molecular layer and Purkinje cells in the cerebellar cortex of the rat. The electrophysiological data were combined with a morphological study of the recorded cells using biocytin or Lucifer yellow staining. Thirty-one interneuron-Purkinje cell pairs were obtained, and 11 of them were recovered morphologically. The age of the rats ranged from 11 to 31 d after birth. During this period synaptic maturation resulted in an 11-fold decrease in the average current evoked in a Purkinje cell by a spike in a presynaptic interneuron. Unitary IPSCs in younger animals exhibited paired-pulse depression, whereas paired-pulse facilitation was found in more mature animals. These data suggest that reduction in transmitter release probability contributed to the developmental decrease of unitary IPSCs. However, additional mechanisms at both presynaptic and postsynaptic loci should also be considered. The decrease of the average synaptic current evoked in a Purkinje cell by an action potential in a single interneuron suggests that as development proceeds interneuron activities must be coordinated to inhibit efficiently Purkinje cells.
    BibTeX:
    @article{PouzatHestrin_1997,
      author = {Pouzat, C. and Hestrin, S.},
      title = {Developmental regulation of basket/stellate cell-->Purkinje cell synapses in the cerebellum.},
      journal = {J Neurosci},
      year = {1997},
      volume = {17},
      number = {23},
      pages = {9104--9112},
      url = {http://www.jneurosci.org/cgi/content/abstract/17/23/9104}
    }
    
    Wahl, L., Pouzat, C. & Stratford, K. Monte Carlo simulation of fast excitatory synaptic transmission at a hippocampal synapse. 1996 J Neurophysiol
    Vol. 75(2), pp. 597-608 
    article URL 
    Abstract: 1. A simulation of fast excitatory synaptic transmission at a hippocampal synapse is presented. Individual neurotransmitter molecules are followed as they diffuse through the synaptic cleft and interact with the postsynaptic receptors. The ability of the model to reproduce published results of patch-clamp experiments on CA3 pyramidal cells is illustrated; parameters of the model that affect the time course and variability of the excitatory postsynaptic current (EPSC) are then investigated. 2. To simulate an EPSC, we release 4,000 neurotransmitter molecules simultaneously from a point source centered 15 nm above a rectangular grid of 14 x 14 postsynaptic receptors. The simulated EPSC at room temperature has a 10-90% rise time of 0.28 ms and a peak open probability of 0.27, and decays with a time constant of 2.33 ms, comparing well with values in the literature. 3. To simulate changes in temperature, we use a 10 degrees temperature coefficient (Q10) for diffusion of 1.3 and apply a Q10 of 3.0 to all the rate constants of the kinetic scheme. At 37 degrees C, the 10-90 rise time is 0.07 ms, the peak open probability is 0.56, and the decay time constant is 0.70 ms. The coefficient of variation (CV) at the peak of the EPSC is 9.4% at room temperature; at 37 degrees C, the CV at the peak drops to 6.6 4. We use the diffusion coefficient of glutamine, 7.6 x 10(-6) cm2/s, to model the random movement of glutamate molecules in the synaptic cleft. Slower rates of diffusion increase the peak response and slow the time course of decay of the EPSC. 5. Random variations in release site position have little effect on the time course of the average EPSC or on the CV of the peak response. We simulate a dose-response curve for the effects of releasing between 100 and 7,500 neurotransmitter molecules per vesicle. The half-maximal response occurs for 1,740 molecules. For a simulation with 100 postsynaptic receptors and a diffusion coefficient of 2.0 x 10(-6) cm2/s, 4,000 molecules approaches a saturating dose. 6. Changes to the width of the synaptic cleft, or to the number and spacing of the postsynaptic receptors, have marked effects on the peak height of the simulated EPSC. 7. We extend the model to include a spherical vesicle (50 nm diam) connected to the synaptic cleft by a cylindrical pore 15 nm long. Neurotransmitter molecules are randomly distributed within the vesicle and allowed to diffuse into the synaptic cleft through the pore, which opens to its full diameter in one time step. We find that the pore must open to a diameter of > or = 7 nm within 1 microsecond in order to match the time courses of EPSCs in the literature.
    BibTeX:
    @article{WahlEtAL_1996,
      author = {Wahl, L.M. and Pouzat, C. and Stratford, K.J.},
      title = {Monte Carlo simulation of fast excitatory synaptic transmission at a hippocampal synapse.},
      journal = {J Neurophysiol},
      year = {1996},
      volume = {75},
      number = {2},
      pages = {597--608},
      url = {http://intl-jn.physiology.org/cgi/content/abstract/75/2/597}
    }
    
    Sihra, T., Nairn, A., Kloppenburg, P., Lin, Z. & Pouzat, C. A role for calcineurin (protein phosphatase-2B) in the regulation of glutamate release. 1995 Biochem Biophys Res Commun
    Vol. 212(2), pp. 609-616 
    article URL 
    Abstract: Previous studies have shown that 4-aminopyridine (4AP) induced Ca-influx effects the release of glutamate from nerve terminals (synaptosomes) isolated from rat cerebral cortex. We now show that the Ca-dependent component of this release is potentiated by preincubation of the synaptosomes with the immunosuppressant, FK506, an inhibitor of protein phosphatase-2B (calcineurin). FK506 did not inhibit the Ca-independent release of glutamate from a cytosolic pool. Examination of the effect of FK506 on the influx of Ca elicited by 4AP indicated that inhibition of calcineurin activity resulted in an increase of voltage-dependent Ca-influx. Based on these results, we suggest that protein dephosphorylation effected by calcineurin may suppress voltage-dependent Ca-channel activity and in so doing inhibits evoked glutamate release. Activation of calcineurin produced by initial Ca-entry may represent a negative feedback to limit the activity of Ca-channels coupled to the release of glutamate.
    BibTeX:
    @article{ShiraEtAl_1995,
      author = {Sihra, T.S. and Nairn, A.C. and Kloppenburg, P. and Lin, Z. and Pouzat, C.},
      title = {A role for calcineurin (protein phosphatase-2B) in the regulation of glutamate release.},
      journal = {Biochem Biophys Res Commun},
      year = {1995},
      volume = {212},
      number = {2},
      pages = {609--616},
      url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7542882}
    }
    

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