The effect of morphology upon electrophysiological responses of retinal ganglion cells: simulation results

Retinal ganglion cells (RGCs) display differences in their morphology and intrinsic electrophysiology. The goal of this study is to characterize the ionic currents that explain the behavior of ON and OFF RGCs and to explore if all morphological types of RGCs exhibit the phenomena described in electrophysiological data. We extend our previous single compartment cell models of ON and OFF RGCs to more biophysically realistic multicompartment cell models and investigate the effect of cell morphology on intrinsic electrophysiological properties. The membrane dynamics are described using the Hodgkin - Huxley type formalism. A subset of published patch-clamp data from isolated intact mouse retina is used to constrain the model and another subset is used to validate the model. Two hundred morphologically distinct ON and OFF RGCs are simulated with various densities of ionic currents in different morphological neuron compartments. Our model predicts that the differences between ON and OFF cells are explained by the presence of the low voltage activated calcium current in OFF cells and absence of such in ON cells. Our study shows through simulation that particular morphological types of RGCs are capable of exhibiting the full range of phenomena described in recent experiments. Comparisons of outputs from different cells indicate that the RGC morphologies that best describe recent experimental results are ones that have a larger ratio of soma to total surface area

Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations

The mechanisms of seizure emergence, and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. Our study shows that the transition to seizure is not a sudden phenomenon,but a slow process characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by the synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We show that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Feasibility of Nitrogen Doped Ultrananocrystalline Diamond Microelectrodes for Electrophysiological Recording From Neural Tissue

Neural prostheses that can monitor the physiological state of a subject are becoming clinically viable through improvements in the capacity to record from neural tissue. However, a significant limitation of current devices is that it is difficult to fabricate electrode arrays that have both high channel counts and the appropriate electrical properties required for neural recordings. In earlier work, we demonstrated nitrogen doped ultrananocrystalline diamond (N-UNCD) can provide efficacious electrical stimulation of neural tissue, with high charge injection capacity, surface stability and biocompatibility. In this work, we expand on this functionality to show that N-UNCD electrodes can also record from neural tissue owing to its low electrochemical impedance. We show that N-UNCD electrodes are highly flexible in their application, with successful recordings of action potentials from single neurons in an in vitro retina preparation, as well as local field potential responses from in vivo visual cortex tissue. Key properties of N-UNCD films, combined with scalability of electrode array fabrication with custom sizes for recording or stimulation along with integration through vertical interconnects to silicon based integrated circuits, may in future form the basis for the fabrication of versatile closed-loop neural prostheses that can both record and stimulate

Soft, flexible freestanding neural stimulation and recording electrodes fabricated from reduced graphene oxide

There is an urgent need for conductive neural interfacing materials that exhibit mechanically compliant properties, while also retaining high strength and durability under physiological conditions. Currently, implantable electrode systems designed to stimulate and record neural activity are composed of rigid materials such as crystalline silicon and noble metals. While these materials are strong and chemically stable, their intrinsic stiffness and density induce glial scarring and eventual loss of electrode function in vivo. Conductive composites, such as polymers and hydrogels, have excellent electrochemical and mechanical properties, but are electrodeposited onto rigid and dense metallic substrates. In the work described here, strong and conductive microfibers (40-50 μm diameter) wet-spun from liquid crystalline dispersions of graphene oxide are fabricated into freestanding neural stimulation electrodes. The fibers are insulated with parylene-C and laser-treated, forming brush electrodes with diameters over 3.5 times that of the fiber shank. The fabrication method is fast, repeatable, and scalable for high-density 3D array structures and does not require additional welding or attachment of larger electrodes to wires. The electrodes are characterized electrochemically and used to stimulate live retina in vitro. Additionally, the electrodes are coated in a water-soluble sugar microneedle for implantation into, and subsequent recording from, visual cortex

Retinal ganglion cells electrophysiology: The effect of cell morphology on impulse waveform

There are 16 morphologically defined classes of rats retinal ganglion cells (RGCs). Using computer simulation of a realistic anatomically correct A1 mouse RGC, we investigate the effect of the cell's morphology on its impulse waveform, using the first-,

On Transient qualification of LOBI/MOD2, SPES, LSTF and BETHSY nodalizations for RELAP5/MOD2 code

The results obtained in a more-than-a-decade application of thermal-hydraulic system codes to the analysis of experiments performed in Integral Test Facilities (ITF) and Separate Effect test Facilities (SETF) including the participation to several International Standard Problems (ISP) and Standard Problem Exercises (SPE), organized by OECD/NEA/CSNI (Organization for Economic Cooperation and Development / Nuclear Energy Agency / Committee on the Safety of Nuclear Installations) and by IAEA (international Atomic Energy Agency), respectively, suggested the need for new methods and procedures for code application. The words nodalization-qualification, qualitative-accuracy-evaluation, quantitative-accuracy-evaluation, and acceptability-thresholds were introduced. The present document deals with nodalization qualification at the transient level for the LOBI/mod2 available at the EURATOM JRC of Ispra (Italy), the SPES, available at the SIET research center in Piacenza, Italy, the LSTF available at the Tokai-Mura Research Center of JAERI in Japan and the BETHSY available at the CEA-CENG research center in Grenoble, France. The activity in this case is based upon the analysis of one experiment performed in each ITF, respectively: criteria for accepting the results of the comparison with calculated data are fixed from the application of the FFTBM (Fast Fourier Transform Based Method)