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Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

ABSTRACT: High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

SUBMITTER: Huff TB

PROVIDER: S-EPMC3048389 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

Huff Terry B TB Shi Yunzhou Y Sun Wenjing W Wu Wei W Shi Riyi R Cheng Ji-Xin JX

PloS one 20110303 3

High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retractio ...[more]

PMID: 21390223

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Project description:BackgroundApproaches to predictably control neural oscillations are needed to understand their causal role in brain function in healthy or diseased states and to advance the development of neuromodulation therapies.ObjectiveWe present a closed-loop neural control and optimization framework to actively suppress or amplify low-frequency neural oscillations observed in local field potentials in real-time by using electrical stimulation. The rationale behind this control approach and our working hypothesis is that neural oscillatory activity evoked by electrical pulses can suppress or amplify spontaneous oscillations via destructive or constructive interference when the pulses are continuously delivered with appropriate amplitudes and at precise phases of the modulated oscillations in a closed-loop scheme.MethodsWe tested our hypothesis in two nonhuman primates that exhibited a robust increase in low-frequency (8-30 Hz) oscillatory power in the subthalamic nucleus (STN) following administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To test our neural control approach, we targeted 8-17 Hz oscillations and used electrode arrays and electrical stimulation waveforms similar to those used in humans chronically implanted with brain stimulation systems. Stimulation parameters that maximize the suppression or amplification of neural oscillations were predicted using mathematical models of the stimulation evoked oscillations.ResultsOur neural control and optimization approach was capable of actively and robustly suppressing or amplifying oscillations in the targeted frequency band (8-17 Hz) in real-time in the studied subjects.ConclusionsThe results from this study support our hypothesis and suggest that the proposed neural control framework allows one to characterize in controlled experiments the functional role of frequency-specific neural oscillations by using electrodes and stimulation waveforms currently being employed in humans.

Dataset Information

Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

Publications

Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

Similar Datasets

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