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Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

ABSTRACT: Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

SUBMITTER: Mitew S

PROVIDER: S-EPMC5778130 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

Mitew Stanislaw S Gobius Ilan I Fenlon Laura R LR McDougall Stuart J SJ Hawkes David D Xing Yao Lulu YL Bujalka Helena H Gundlach Andrew L AL Richards Linda J LJ Kilpatrick Trevor J TJ Merson Tobias D TD Emery Ben B

Nature communications 20180122 1

Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an incre ...[more]

PMID: 29358753

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Project description:IntroductionPropofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS.MethodsThis retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months.ResultsSignificantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: β = 2.64, p < 0.01; theta: β = 2.11, p < 0.01; alpha: β = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups.ConclusionOptimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS.Trial registrationChinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021-Retrospectively registered.

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Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

Publications

Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

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