Selective activation of functional muscle groups through stimulation of spinal motor pools

Journal ArticleA microelectrode was used to stimulate motor neurons in the lumbo-sacral spinal cord of adult cats. Consistent with spinal cord anatomical studies, we found that the motor neurons responsible for activation of individual muscle groups are situated together in specific areas of the cord, forming motor pools. Localized spinal cord stimulation of these motor pools enables selective activation of individual muscle groups. By modulating the magnitude of stimulation at different sites in the motor pools, we should be able to selectively activate different muscle groups to produce desired levels of contraction and controlled limb movements

Electrical stimulation of the ventral lumbo-sacral spinal cord results in mixed recruitment order of quadriceps and tibialis anterior motor units

Journal ArticlePulse width modulated, twitch recruitment curves for quadriceps and tibialis anterior were obtained by stimulating their respective motor activation pools in the ventral lumbo-sacral portion of the spinal cord. The duration of the twitch responses were analyzed as a function of stimulus strength to determine the order of motor unit recruitment. It was found that activating the quadriceps or tibialis anterior by stimulating the spinal cord resulted in a predominantly mixed recruitment order of its motor units. These results suggest that spinal cord stimulation could have application in future neuromuscular stimulation systems where normal recruitment order of muscle fibers is desired for producing fine control of muscle activity and enhancing fatigue resistance

In vitro biocompatibility evaluation of functional electrically stimulating microelectrodes on primary glia

Neural interfacing devices interact with the central nervous system to alleviate functional deficits arising from disease or injury. This often entails the use of invasive microelectrode implants that elicit inflammatory responses from glial cells and leads to loss of device function. Previous work focused on improving implant biocompatibility by modifying electrode composition; here, we investigated the direct effects of electrical stimulation on glial cells at the electrode interface. A high-throughput in vitro system that assesses primary glial cell response to biphasic stimulation waveforms at 0 mA, 0.15 mA, and 1.5 mA was developed and optimized. Primary mixed glial cell cultures were generated from heterozygous CX3CR-1+/EGFP mice, electrically stimulated for 4 h/day over 3 days using 75 μm platinum-iridium microelectrodes, and biomarker immunofluorescence was measured. Electrodes were then imaged on a scanning electron microscope to assess sustained electrode damage. Fluorescence and electron microscopy analyses suggest varying degrees of localized responses for each biomarker assayed (Hoescht, EGFP, GFAP, and IL-1β), a result that expands on comparable in vivo models. This system allows for the comparison of a breadth of electrical stimulation parameters, and opens another avenue through which neural interfacing device developers can improve biocompatibility and longevity of electrodes in tissue

Suppressing the Excitability of Spinal Motoneurons by Extracellularly-Applied Electrical Fields: Insights from Computer Simulations

The effect of extracellularly applied electrical fields on neuronal excitability and firing behavior is attributed to the interaction between neuronal morphology and the spatial distribution and level of differential polarization induced by the applied field in different elements of the neuron. The presence of voltage-gated ion channels that mediate persistent inward currents (PICs) on the dendrites of spinal motoneurons enhances the influence of electrical fields on the motoneuronal firing behavior. The goal of the present study was to investigate, with a realistic motoneuron computer model, the effects of extracellularly applied electrical fields on the excitability of spinal motoneurons with the aim of reducing the increased motoneuronal excitability after spinal cord injury (SCI). Our results suggest that electrical fields could suppress the excitability of motoneurons and reduce their firing rate significantly by modulating the magnitude of their dendritic PIC. This effect was achieved at different field directions, intensities, and polarities. The reduction in motoneuronal firing rate resulted from the reduction in the magnitude of the dendritic PIC reaching the soma by the effect of the applied electrical field. This reduction in PIC was attributed to the dendritic field-induced differential polarization and the nonlinear current-voltage relationship of the dendritic PIC-mediating channels. Because of the location of the motoneuronal somata and initial segment with respect to the dendrites, these structures were minimally polarized by the applied field compared with the extended dendrites. In conclusion, electrical fields could be used for suppressing the hyperexcitability of spinal motoneurons after SCI and reducing the level of spasticity

Suppressing the Excitability of Spinal Motoneurons by Extracellularly-Applied Electrical Fields: Insights from Computer Simulations

The effect of extracellularly applied electrical fields on neuronal excitability and firing behavior is attributed to the interaction between neuronal morphology and the spatial distribution and level of differential polarization induced by the applied field in different elements of the neuron. The presence of voltage-gated ion channels that mediate persistent inward currents (PICs) on the dendrites of spinal motoneurons enhances the influence of electrical fields on the motoneuronal firing behavior. The goal of the present study was to investigate, with a realistic motoneuron computer model, the effects of extracellularly applied electrical fields on the excitability of spinal motoneurons with the aim of reducing the increased motoneuronal excitability after spinal cord injury (SCI). Our results suggest that electrical fields could suppress the excitability of motoneurons and reduce their firing rate significantly by modulating the magnitude of their dendritic PIC. This effect was achieved at different field directions, intensities, and polarities. The reduction in motoneuronal firing rate resulted from the reduction in the magnitude of the dendritic PIC reaching the soma by the effect of the applied electrical field. This reduction in PIC was attributed to the dendritic field-induced differential polarization and the nonlinear current-voltage relationship of the dendritic PIC-mediating channels. Because of the location of the motoneuronal somata and initial segment with respect to the dendrites, these structures were minimally polarized by the applied field compared with the extended dendrites. In conclusion, electrical fields could be used for suppressing the hyperexcitability of spinal motoneurons after SCI and reducing the level of spasticity

Brazalete abierto con remates en en forma de copa con punta interior - TVA003

Proyectos del Plan Nacional I+D+I con referencias PB94-0129, PB97-1132, BHA 2002-00138, HUM 2006-06250/HISTProyectos de la CAM con referencias 06/0020/1997, 06/0094/1998, 06/0090/2000, 06/0043/2001Programa Consolider-Ingenio 2010 con sigla CSD2007-00058NoMuseu Nacional de Arqueologia (Lisboa)Torre VâBrazalete abierto con remates en en forma de copa con punta interio

Suppressing the Excitability of Spinal Motoneurons by Extracellularly-Applied Electrical Fields: Insights from Computer Simulations

The effect of extracellularly applied electrical fields on neuronal excitability and firing behavior is attributed to the interaction between neuronal morphology and the spatial distribution and level of differential polarization induced by the applied field in different elements of the neuron. The presence of voltage-gated ion channels that mediate persistent inward currents (PICs) on the dendrites of spinal motoneurons enhances the influence of electrical fields on the motoneuronal firing behavior. The goal of the present study was to investigate, with a realistic motoneuron computer model, the effects of extracellularly applied electrical fields on the excitability of spinal motoneurons with the aim of reducing the increased motoneuronal excitability after spinal cord injury (SCI). Our results suggest that electrical fields could suppress the excitability of motoneurons and reduce their firing rate significantly by modulating the magnitude of their dendritic PIC. This effect was achieved at different field directions, intensities, and polarities. The reduction in motoneuronal firing rate resulted from the reduction in the magnitude of the dendritic PIC reaching the soma by the effect of the applied electrical field. This reduction in PIC was attributed to the dendritic field-induced differential polarization and the nonlinear current-voltage relationship of the dendritic PIC-mediating channels. Because of the location of the motoneuronal somata and initial segment with respect to the dendrites, these structures were minimally polarized by the applied field compared with the extended dendrites. In conclusion, electrical fields could be used for suppressing the hyperexcitability of spinal motoneurons after SCI and reducing the level of spasticity

Modulation of Motoneuronal Firing Behavior After Spinal Cord Injury Using Intraspinal Microstimulation Current Pulses: A Modeling Study

We simulated the effects of delivering focal electrical stimuli to the central nervous system to modulate the firing rate of neurons and alleviate motor disorders. Application of these stimuli to the spinal cord to reduce the increased excitability of motoneurons and resulting spasticity after spinal cord injury (SCI) was examined by means of a morphologically detailed computer model of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well as biphasic charge-balanced and charge-imbalanced pulses were examined. Our results suggest that suprathreshold high-frequency sinusoidal or rectangular current pulses could inactivate the Na+ channels in the soma and initial segment, and block action potentials from propagating through the axon. Subthreshold biphasic charge-imbalanced pulses reduced the motoneuronal firing rate significantly (up to approximately 25% reduction). The reduction in firing rate was achieved through stimulation-induced hyperpolarization generated in the first node of Ranvier. Because of their low net DC current, these pulses could be tolerated safely by the tissue. To deliver charge-imbalanced pulses with the lowest net DC current and induce the largest reduction in motoneuronal firing rate, we studied the effect of various charge-imbalanced pulse parameters. Short pulse durations were found to induce the largest reduction in firing rate for the same net DC level. Subthreshold high-frequency sinusoidal and rectangular current pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed electrical stimulation paradigms could provide potential rehabilitation interventions for suppressing the excitability of neurons to reduce the severity of motor disorders after injury to the central nervous system

Simulation of Ca+2 Persistent Inward Currents in Spinal Motoneurons: Mode of Activation and Integration of Synaptic Inputs

The goal of this study was to investigate the nature of activation of the dendritic calcium persistent inward current (Ca2+ PIC) and its contribution to the enhancement and summation of synaptic inputs in spinal motoneurones. A compartmental cable model of a catα-motoneurone was developed comprising the realistic dendritic distribution of Ia-afferent synapses and low-voltage-activated L-type calcium (Cav1.3) channels distributed over the dendrites in a manner that was previously shown to match a wide set of experimental measurements. The level of synaptic activation was systematically increased and the resulting firing rate, somatic and dendritic membrane potentials, dendritic Cav1.3 channel conductance, and dendritic Ca2+ PIC were measured. Our simulation results suggest that during cell firing the dendritic Ca2+ PIC is not activated in an all-or-none manner. Instead, it is initially activated in a graded manner with increasing synaptic input until it reaches its full activation level, after which additional increases in synaptic input result in minimal changes in the Ca2+ PIC (PIC saturated). The range of graded activation of Ca2+ PICoccurs when the cell is recruited and causes a steep increase in the firing frequency as the synaptic current is increased, coinciding with the secondary range of the synaptic frequency–current (F–I)relationship.Once theCa2+ PICissaturated the slope of theF–I relationship is reduced, corresponding to the tertiary range of firing.When the post-spike after-hyperpolarization (AHP) is blocked, either directly by blocking the calcium-activated potassium channels, or indirectly by blocking the sodium spikes, the PIC is activated in an all-or-none manner with increasing synaptic input. Thus, the AHP serves to limit the depolarization of the cell during firing and enables graded, rather than all-or-none, activation of the Ca2+ PIC. The graded activation of the Ca2+ PIC with increasing synaptic input results in a graded (linear) enhancement and linear summation of synaptic inputs. In contrast, the saturated Ca2+ PIC enhances synaptic inputs by a constant amount (constant current), and leads to less-than linear summation of multiple synaptic inputs. These model predictions improve our understanding of the mode of activation of the dendritic Ca2+ PIC and its role in the enhancement and integration of synaptic inputs