Frequency-dependent antidromic activation in thalamocortical relay neurons: effects of synaptic inputs

Yi, Guosheng; Grill, Warren M.

doi:10.1088/1741-2552/aacbff

Cited by 16 publications

(22 citation statements)

References 66 publications

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“…We defined 50 particles as a time series of electrode currents. The extracellular medium was assumed to be infinite homogenous and isotropic with a conductivity of σ = 0.303 S/m [52,53]. For a segment at location (x, y, z), the extracellular potential V ext was calculated as [53,54] V ext x; y; z ð Þ ¼ I ext 4ps ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi ffi…”

Section: Plos Computational Biologymentioning

confidence: 99%

Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

Grill

2020

PLoS Comput Biol

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The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na + channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity.

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Section: Plos Computational Biologymentioning

confidence: 99%

Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

Grill

2020

PLoS Comput Biol

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“…Careful control of the temporal dynamics of neuronal activation can be critical important for the application of therapeutic ICMS. Modeling suggests both excitatory and inhibitory input greatly influence the ability for neurons to entrain ICMS [32]. Because this baseline excitability can be impacted by ongoing neuronal activity, it is possible that the activation threshold is also impacted.…”

Section: Stimulation Polarity and Asymmetry Modulate The Temporal Netmentioning

confidence: 99%

“…8). Because fiber geometry, frequency, and the excitatory and inhibitory balance greatly influence the level of entrainment [32], it will be interesting to investigate how waveform modulates these effects to better inform clinical therapies employing electrical stimulation.…”

Section: Asymmetric Anodic Waveforms As An Effective Tool In Neural Pmentioning

confidence: 99%

“…Electrical stimulation often activates axon nodes or terminals as opposed to cell bodies due to the higher excitability, thus the local axonal projections greatly influence the spatial distribution of activated neurons [16,[28][29][30]. Additionally, neuronal entrainment to stimulation depends on the site of activation on the neuron, the afterpotential dynamics, and the relative amount of excitatory and inhibitory input to the cells [23,31,32]. Our group recently published a study demonstrating that frequency can also modulate the spatial pattern of neuronal activation [24].…”

Section: Introductionmentioning

confidence: 99%

“…Modeling [33][34][35] and in vivo [27][28][29]36] studies have demonstrated that orthodromic activation of cells and antidromic activation of passing fibers have similar thresholds when using monophasic stimulation pulses [21]. Therefore, it has been proposed that modulation of the likelihood of a neuronal element being activated by electric field may change the neuronal response to electrical stimulation [21,22,32]. Although monophasic waveforms have lower activation thresholds, convention is to use charge balanced biphasic waveforms to prevent electrode degradation; however, there can be safety benefits to slight charge imbalance [37].…”

Section: Introductionmentioning

confidence: 99%

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In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Steiger

Eles

Ludwig

et al. 2019

Preprint

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250 word maximum Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e. increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10 Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.Significance Statement: Electrical stimulation has promise to restore sensation and motor function, as well as treat the symptoms of several neurological disorders. However, the mechanisms responsible for the beneficial effects of stimulation are not fully understood. This work supports modeling predictions by demonstrating that modulation of the stimulation waveform dramatically affects the spatial recruitment and activity level of neurons in vivo. These findings suggest that stimulation waveform symmetry represents a parameter that may be able to increase the dynamic range of stimulation ap-plications. Further characterization of these parameters with frequency, and amplitude could provide further insight into the mechanisms of electrical stimulation.

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In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Stieger

Eles

Ludwig

et al. 2020

J of Neuroscience Research

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Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e., increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two‐photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10‐Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.

show abstract

Frequency-dependent antidromic activation in thalamocortical relay neurons: effects of synaptic inputs

Cited by 16 publications

References 66 publications

Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

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