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      Efficient implementation of a real-time estimation system for thalamocortical hidden Parkinsonian properties

      Scientific Reports
      Springer Nature

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          Adaptive exponential integrate-and-fire model as an effective description of neuronal activity.

          We introduce a two-dimensional integrate-and-fire model that combines an exponential spike mechanism with an adaptation equation, based on recent theoretical findings. We describe a systematic method to estimate its parameters with simple electrophysiological protocols (current-clamp injection of pulses and ramps) and apply it to a detailed conductance-based model of a regular spiking neuron. Our simple model predicts correctly the timing of 96% of the spikes (+/-2 ms) of the detailed model in response to injection of noisy synaptic conductances. The model is especially reliable in high-conductance states, typical of cortical activity in vivo, in which intrinsic conductances were found to have a reduced role in shaping spike trains. These results are promising because this simple model has enough expressive power to reproduce qualitatively several electrophysiological classes described in vitro.
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            Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition.

            Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders. However, fundamental questions remain about the effects of DBS on neurons surrounding the electrode. Experimental studies have produced apparently contradictory results showing suppression of activity in the stimulated nucleus, but increased inputs to projection nuclei. We hypothesized that cell body firing does not accurately reflect the efferent output of neurons stimulated with high-frequency extracellular pulses, and that this decoupling of somatic and axonal activity explains the paradoxical experimental results. We studied stimulation using the combination of a finite-element model of the clinical DBS electrode and a multicompartment cable model of a thalamocortical (TC) relay neuron. Both the electric potentials generated by the electrode and a distribution of excitatory and inhibitory trans-synaptic inputs induced by stimulation of presynaptic terminals were applied to the TC relay neuron. The response of the neuron to DBS was primarily dependent on the position and orientation of the axon with respect to the electrode and the stimulation parameters. Stimulation subthreshold for direct activation of TC relay neurons caused suppression of intrinsic firing (tonic or burst) activity during the stimulus train mediated by activation of presynaptic terminals. Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon. This independence of firing in the cell body and axon resolves the apparently contradictory experimental results on the effects of DBS. In turn, the results of this study support the hypothesis of stimulation-induced modulation of pathological network activity as a therapeutic mechanism of DBS.
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              Bursting of thalamic neurons and states of vigilance.

              This article addresses the functional significance of the electrophysiological properties of thalamic neurons. We propose that thalamocortical activity, is the product of the intrinsic electrical properties of the thalamocortical (TC) neurons and the connectivity their axons weave. We begin with an overview of the electrophysiological properties of single neurons in different functional states, followed by a review of the phylogeny of the electrical properties of thalamic neurons, in several vertebrate species. The similarity in electrophysiological properties unambiguously indicates that the thalamocortical system must be as ancient as the vertebrate branch itself. We address the view that rather than simply relays, thalamic neurons have sui generis intrinsic electrical properties that govern their specific functional dynamics and regulate natural functional states such as sleep and vigilance. In addition, thalamocortical activity has been shown to be involved in the genesis of several neuropsychiatric conditions collectively described as thalamocortical dysrhythmia syndrome.
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                Author and article information

                Journal
                10.1038/srep40152
                http://creativecommons.org/licenses/by/4.0

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