Skander Mensi

Temporal whitening by power-law adaptation in neocortical neurons

Spike-frequency adaptation (SFA) is widespread in the CNS, but its function remains unclear. In neocortical pyramidal neurons, adaptation manifests itself by an increase in the firing threshold and by adaptation currents triggered after each spike. Combining electrophysiological recordings in mice with modeling, we found that these adaptation processes lasted for more than 20 s and decayed over multiple timescales according to a power law. The power-law decay associated with adaptation mirrored and canceled the temporal correlations of input current received in vivo at the somata of layer 2/3 somatosensory pyramidal neurons. These findings suggest that, in the cortex, SFA causes temporal decorrelation of output spikes (temporal whitening), an energy-efficient coding procedure that, at high signal-to-noise ratio, improves the information transfer.

Parameter extraction and classification of three cortical neuron types reveals two distinct adaptation mechanisms

Cortical information processing originates from the exchange of action potentials between many cell types. To capture the essence of these interactions, it is of critical importance to build mathematical models that reflect the characteristic features of spike generation in individual neurons. We propose a framework to automatically extract such features from current-clamp experiments, in particular the passive properties of a neuron (i.e., membrane time constant, reversal potential, and capacitance), the spike-triggered adaptation currents, as well as the dynamics of the action potential threshold. The stochastic model that results from our maximum likelihood approach accurately predicts the spike times, the subthreshold voltage, the firing patterns, and the type of frequency-current curve. Extracting the model parameters for three cortical cell types revealed that cell types show highly significant differences in the time course of the spike-triggered currents and moving threshold, that is, in their adaptation and refractory properties but not in their passive properties. In particular, GABAergic fast-spiking neurons mediate weak adaptation through spike-triggered currents only, whereas regular spiking excitatory neurons mediate adaptation with both moving threshold and spike-triggered currents. GABAergic nonfast-spiking neurons combine the two distinct adaptation mechanisms with reduced strength. Differences between cell types are large enough to enable automatic classification of neurons into three different classes. Parameter extraction is performed for individual neurons so that we find not only the mean parameter values for each neuron type but also the spread of parameters within a group of neurons, which will be useful for future large-scale computer simulations.

Improved similarity measures for small sets of spike trains

Multiple measures have been developed to quantify the similarity between two spike trains. These measures have been used for the quantification of the mismatch between neuron models and experiments as well as for the classification of neuronal responses in neuroprosthetic devices and electrophysiological experiments. Frequently only a few spike trains are available in each class. We derive analytical expressions for the small-sample bias present when comparing estimators of the time-dependent firing intensity. We then exploit analogies between the comparison of firing intensities and previously used spike train metrics and show that improved spike train measures can be successfully used for fitting neuron models to experimental data, for comparisons of spike trains, and classification of spike train data. In classification tasks, the improved similarity measures can increase the recovered information. We demonstrate that when similarity measures are used for fitting mathematical models, all previous methods systematically underestimate the noise. Finally, we show a striking implication of this deterministic bias by reevaluating the results of the single-neuron prediction challenge.

Automated High-Throughput Characterization of Single Neurons by Means of Simplified Spiking Models.

Single-neuron models are useful not only for studying the emergent properties of neural circuits in large-scale simulations, but also for extracting and summarizing in a principled way the information contained in electrophysiological recordings. Here we demonstrate that, using a convex optimization procedure we previously introduced, a Generalized Integrate-and-Fire model can be accurately fitted with a limited amount of data. The model is capable of predicting both the spiking activity and the subthreshold dynamics of different cell types, and can be used for online characterization of neuronal properties. A protocol is proposed that, combined with emergent technologies for automatic patch-clamp recordings, permits automated, in vitro high-throughput characterization of single neurons.

Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter—describing somatic integration—and the spike-history filter—accounting for spike-frequency adaptation—dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations.

Automatic characterization of three cortical neuron types reveals two distinct adaptation mechanisms

It has been established over the last 20 years that simplified spiking neuron models are capable of reproducing the variety of firing patterns that have been found in experimental preparations, including delayed spike onset, bursting, strong or weak adaptation, refractoriness, etc. All of these models belong to the family of generalized integrate-and-fire (IF) models, but vary in the way the standard leaky integrate-and-fire model is generalized. Features to upgrade the simple integrate-and-fire include spike after-currents, dynamic threshold, smooth spike initiation and linearized subthreshold currents. Important questions are then: which of these features are needed for basic cortical computation? How many levels of complexity do we have to add to account for relevant features of cortical dynamics? Is the spike-frequency adaptation mediated by moving thresholds or spike-triggered currents? To answer these question, we developed an efficient method for parameter optimization, that is able to extract some specific features of a neuron from current-clamp experiment. More precisely we are able to estimate the spike-triggered adaptation current that mediates spike-frequency adaptation and the dynamics of the action potential threshold, along with the passive properties of a neuron (i.e. membrane time constant, reverse potential). The method relies on the separation of the parameters affecting the subthreshold voltage and those affecting the firing threshold and its dynamics. We applied our method to three different neuron classes, Fast Spiking (FS) and non-Fast Spiking (nFS) interneurons and Pyramidal neurons (Pyr). The models we extracted reproduces the excitability type of FS, nFS and Pyr neurons to a remarkable degree of accuracy so that above 90 % of the predictable spikes can be predicted while the difference in subthreshold voltage prediction is less than 1.5 mV. We also find that the adaptation is mediated by different processes in different cell types: mostly by the moving threshold for the Pyr, entirely spike-triggered current for the FS, an equal mix of threshold and current for the nFS. Finally, we show that the parameters of the adaptation currents and dynamic threshold can be used for an automatic classification of the electrophysiological traces into three well-separated classes, whereas the passive parameters alone do not contain a sufficient amount of information to do so. We observe that the three neuron types have very contrasting threshold dynamics and that efficient classification can be done using only the parameters regulating the dynamics of the threshold.

Complexity and performance in simple neuron models

The ability of simple mathematical models to predict the activity of single neurons is important for computational neuroscience. In neurons, stimulated by a time-dependent current or conductance, we want to predict precisely the timing of spikes and the sub-threshold voltage. During the last years several models have been tested on this type of data but never compared with the same protocol. One of the major outcome is that, from a certain degree of complexity, all are very efficient and gave statistically indistinguishable results. We studied a class of integrate-and-fire models (IF), with each member of the class implementing a selection of possible improvements: exponential voltage non-linearity1, spike-triggered adaptation current2, spike-triggered change in conductance, moving threshold3, sub-threshold voltage-dependent currents4. Each refinement adds a new term to the equations of the IF model. This IF family is extendable and adaptable to different neuron types and is able to deal with complex neural activities (i.e. adaptation, facilitation, bursting, relative refractoriness, ...). To systematically explore the effects of a given term of the model a new fitting procedure based on linear regression of voltage change5 is used. This method is fast, robust and allows the extraction of all the models parameters from a few seconds recordings of fluctuating injected current and membrane potential with hundreds spikes without any prior knowledge. To investigate the effect of our modifications, we used as training data three different Hodgkin-Huxley-like models, and two experimental recordings of fast spiking and regular spiking cells and then evaluate each IF model on a given test set. We observe that it is possible to fit a model that can reproduce the activity of neurons with high reliability (i.e. almost 100 % of the spike time and less than 1 mV of sub-threshold voltage difference). Using this framework one can classify IF models in terms of complexity and performance and evaluate the importance of each term for different stimulation paradigms.