Automated optimization of a reduced layer 5 pyramidal cell model based on experimental data.

The construction of compartmental models of neurons involves tuning a set of parameters to make the model neuron behave as realistically as possible. While the parameter space of single-compartment models or other simple models can be exhaustively searched, the introduction of dendritic geometry causes the number of parameters to balloon. As parameter tuning is a daunting and time-consuming task when performed manually, reliable methods for automatically optimizing compartmental models are desperately needed, as only optimized models can capture the behavior of real neurons. Here we present a three-step strategy to automatically build reduced models of layer 5 pyramidal neurons that closely reproduce experimental data. First, we reduce the pattern of dendritic branches of a detailed model to a set of equivalent primary dendrites. Second, the ion channel densities are estimated using a multi-objective optimization strategy to fit the voltage trace recorded under two conditions - with and without the apical dendrite occluded by pinching. Finally, we tune dendritic calcium channel parameters to model the initiation of dendritic calcium spikes and the coupling between soma and dendrite. More generally, this new method can be applied to construct families of models of different neuron types, with applications ranging from the study of information processing in single neurons to realistic simulations of large-scale network dynamics

KInNeSS: A Modular Framework for Computational Neuroscience

Making use of very detailed neurophysiological, anatomical, and behavioral data to build biological-realistic computational models of animal behavior is often a difficult task. Until recently, many software packages have tried to resolve this mismatched granularity with different approaches. This paper presents KInNeSS, the KDE Integrated NeuroSimulation Software environment, as an alternative solution to bridge the gap between data and model behavior. This open source neural simulation software package provides an expandable framework incorporating features such as ease of use, scalabiltiy, an XML based schema, and multiple levels of granularity within a modern object oriented programming design. KInNeSS is best suited to simulate networks of hundreds to thousands of branched multu-compartmental neurons with biophysical properties such as membrane potential, voltage-gated and ligand-gated channels, the presence of gap junctions of ionic diffusion, neuromodulation channel gating, the mechanism for habituative or depressive synapses, axonal delays, and synaptic plasticity. KInNeSS outputs include compartment membrane voltage, spikes, local-field potentials, and current source densities, as well as visualization of the behavior of a simulated agent. An explanation of the modeling philosophy and plug-in development is also presented. Further developement of KInNeSS is ongoing with the ultimate goal of creating a modular framework that will help researchers across different disciplines to effecitively collaborate using a modern neural simulation platform.Center for Excellence for Learning Education, Science, and Technology (SBE-0354378); Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

Spiking Dynamics during Perceptual Grouping in the Laminar Circuits of Visual Cortex

Grouping of collinear boundary contours is a fundamental process during visual perception. Illusory contour completion vividly illustrates how stable perceptual boundaries interpolate between pairs of contour inducers, but do not extrapolate from a single inducer. Neural models have simulated how perceptual grouping occurs in laminar visual cortical circuits. These models predicted the existence of grouping cells that obey a bipole property whereby grouping can occur inwardly between pairs or greater numbers of similarly oriented and co-axial inducers, but not outwardly from individual inducers. These models have not, however, incorporated spiking dynamics. Perceptual grouping is a challenge for spiking cells because its properties of collinear facilitation and analog sensitivity to inducer configurations occur despite irregularities in spike timing across all the interacting cells. Other models have demonstrated spiking dynamics in laminar neocortical circuits, but not how perceptual grouping occurs. The current model begins to unify these two modeling streams by implementing a laminar cortical network of spiking cells whose intracellular temporal dynamics interact with recurrent intercellular spiking interactions to quantitatively simulate data from neurophysiological experiments about perceptual grouping, the structure of non-classical visual receptive fields, and gamma oscillations.CELEST, an NSF Science of Learning Center (SBE-0354378); SyNAPSE program of the Defense Advanced Research Project Agency (HR001109-03-0001); Defense Advanced Research Project Agency (HR001-09-C-0011

Spike frequency adaptation affects the synchronization properties of networks of cortical oscillators

Oscillations in many regions of the cortex have common temporal characteristics with dominant frequencies centered around the 40 Hz (gamma) frequency range and the 5–10 Hz (theta) frequency range. Experimental results also reveal spatially synchronous oscillations, which are stimulus dependent (Gray&Singer, 1987;Gray, König, Engel, & Singer, 1989; Engel, König, Kreiter, Schillen, & Singer, 1992). This rhythmic activity suggests that the coherence of neural populations is a crucial feature of cortical dynamics (Gray, 1994). Using both simulations and a theoretical coupled oscillator approach, we demonstrate that the spike frequency adaptation seen in many pyramidal cells plays a subtle but important role in the dynamics of cortical networks. Without adaptation, excitatory connections among model pyramidal cells are desynchronizing. However, the slow processes associated with adaptation encourage stable synchronous behavior

Fractional order impedance models as rising tools for quantification of unconscious analgesia

This research focuses on modeling the diffusion process that occurs in the human body when an analgesic drug is taken up, by using fractional-order impedance models (FOIMs). We discuss the measurement of a suitable feedback signal that can be used in a model-based control strategy. With this knowledge an early dawn concept of a pain sensor is presented. The major challenges that are encountered during this development consist of identification of the patient model, validation of the pain sensor and validation of the effect of the analgesic drug

A biophysical observation model for field potentials of networks of leaky integrate-and-fire neurons

We present a biophysical approach for the coupling of neural network activity as resulting from proper dipole currents of cortical pyramidal neurons to the electric field in extracellular fluid. Starting from a reduced threecompartment model of a single pyramidal neuron, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential that contributes to the local field potential of a neural population. This work aligns and satisfies the widespread dipole assumption that is motivated by the "open-field" configuration of the dendritic field potential around cortical pyramidal cells. Our reduced three-compartment scheme allows to derive networks of leaky integrate-and-fire models, which facilitates comparison with existing neural network and observation models. In particular, by means of numerical simulations we compare our approach with an ad hoc model by Mazzoni et al. [Mazzoni, A., S. Panzeri, N. K. Logothetis, and N. Brunel (2008). Encoding of naturalistic stimuli by local field potential spectra in networks of excitatory and inhibitory neurons. PLoS Computational Biology 4 (12), e1000239], and conclude that our biophysically motivated approach yields substantial improvement.Comment: 31 pages, 4 figure

The Effect of synchronized inputs at the single neuron level

It is commonly assumed that temporal synchronization of excitatory synaptic inputs onto a single neuron increases its firing rate. We investigate here the role of synaptic synchronization for the leaky integrate-and-fire neuron as well as for a biophysically and anatomically detailed compartmental model of a cortical pyramidal cell. We find that if the number of excitatory inputs, N, is on the same order as the number of fully synchronized inputs necessary to trigger a single action potential, N_t, synchronization always increases the firing rate (for both constant and Poisson-distributed input). However, for large values of N compared to N_t, ''overcrowding'' occurs and temporal synchronization is detrimental to firing frequency. This behavior is caused by the conflicting influence of the low-pass nature of the passive dendritic membrane on the one hand and the refractory period on the other. If both temporal synchronization as well as the fraction of synchronized inputs (Murthy and Fetz 1993) is varied, synchronization is only advantageous if either N or the average input frequency, ƒ(in), are small enough