Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro.

A proof of concept for the evaluation of external nerve and muscle fiber excitation with the finite element software COMSOL Multiphysics, formerly known as FEMLAB, is presented. This software allows the simultaneous solution of fiber excitation by 1D models of the Hodgkin-Huxley type which are embedded in a volume conductor where the electric field is mainly dominated by the electrode currents. This way the presented bidomain model includes the interaction between electrode currents and transmembrane currents during the excitation process. Especially for direct muscle fiber stimulation (cardiac muscle, denervated muscle) the effects from secondary currents from large populations of excited fibers seem to be significant. The method has many applications, for example, the relation between stimulus parameters and fiber recruitment can be analyzed.

The complete denervation of muscles leads to changes in the muscle fibers as well as in the surrounding tissue. Concerning excitability the most important changes are reductions in fiber diameter, in muscle cross-sectional area, and in electrical conductivity of the muscle tissue. These changes can be partially reversed by intensive electrical stimulation. Evaluation of a 3D finite element axial symmetric model of the human thigh shows that the training leads to a reduction in threshold values between 17 and 51 percent, depending on the position of the fiber in the thigh. Single parameter variation clarifies the influence of each of the different factors. The electrode position was found to be most effective with the electrodes as far apart from each other as possible. Due to (i) comparatively higher changes in potentials at the distal electrode; and (ii) variations in sodium channel dynamics, lowest threshold values can be reached with a hyperpolarizing first phase of the biphasic impulse at the distal electrode. The tissue of the denervated muscle is known to be highly inhomogeneous. Simulations demonstrate that the related irregularities in the field can actually initiate fiber activation. 3D finite element simulations show the overall positive effects of FES on muscle tissue, especially an improved excitability of the muscle fibers. Furthermore the method gives an insight into the relations between potential distribution, electrode position, geometric effects, and muscle fiber activation that cannot be obtained by measurements.

A finite-element model of the human thigh was coupled with a 1-D compartment model to simulate the excitation of denervated muscle fibers with a needle electrode. For short electrode-fiber distances, the specific characteristics of the needle geometry determined the areas of lowest threshold values. With increasing distance, these areas shifted toward the needle's center of charge. Comparison of the 1-D model with a 3-D fiber model showed that the assumption of rotational symmetry underlying the 1-D model leads to an overestimation of thresholds. For a 40- micro-diameter fiber stimulated with 50 micross pulses at electrode-fiber distances between 50 microm and 1 mm, the 1-D/3-D threshold ratios were between 1.14 and 1.35 for the muscle fiber model, and between 1.11 and 1.17 for Hodgkin-Huxley membrane properties at 20 degrees C. For both membrane models, the deviation was more pronounced for large fiber diameters and short stimulation pulses. Qualitative results of the 1-D model like voltage-distance relations and predictions of spike initiation sites were correct.