Correlative study using structural MRI and super-resolution microscopy to detect structural alterations induced by long-term optogenetic stimulation of striatal medium spiny neurons

Yoshifumi Abe, Yuji Komaki, Fumiko Seki, Shinsuke Shibata, Hideyuki Okano, Kenji Tanaka

Research output: Contribution to journalArticle

Abstract

Striatal medium spiny neurons (MSNs) control motor function. Hyper- or hypo-activity of MSNs coincides with basal ganglia-related movement disorders. Based on the assumption that lasting alterations in neuronal activity lead to structural changes in the brain, understanding these structural alterations may be used to infer MSN functional abnormalities. To infer MSN function from structural data, understanding how long-lasting alterations in MSN activity affect brain morphology is essential. To address this, we utilized a simplified model of functional induction by stimulating MSNs expressing channelrhodopsin 2 (ChR2). Subsequent structural alterations which induced long-term activity changes in these MSNs were investigated in the striatal pathway and its associated regions by diffusion tensor imaging (DTI) and histological assessment with super-resolution microscopy. DTI detected changes in the striatum, substantia nigra, and motor cortex. Histological assessment found a reduction in the diameter of myelinated cortical axons as well as MSN dendrites and axons. The structural changes showed a high correlation between DTI parameters and histological data. These results demonstrated that long-term neural activation in the MSNs alters the diameter of MSN and cortical neurons fibers. This study provides a tool for understanding the causal relationship between functional and structural alterations.

Original languageEnglish
Pages (from-to)163-174
Number of pages12
JournalNeurochemistry International
Volume125
DOIs
Publication statusPublished - 2019 May 1

Fingerprint

Optogenetics
Corpus Striatum
Microscopy
Neurons
Diffusion Tensor Imaging
Axons
Movement Disorders
Motor Cortex
Brain
Motor Neurons
Substantia Nigra
Dendrites
Basal Ganglia

Keywords

  • Axon
  • DTI
  • Medium spiny neuron
  • Myelin
  • Optogenetics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

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abstract = "Striatal medium spiny neurons (MSNs) control motor function. Hyper- or hypo-activity of MSNs coincides with basal ganglia-related movement disorders. Based on the assumption that lasting alterations in neuronal activity lead to structural changes in the brain, understanding these structural alterations may be used to infer MSN functional abnormalities. To infer MSN function from structural data, understanding how long-lasting alterations in MSN activity affect brain morphology is essential. To address this, we utilized a simplified model of functional induction by stimulating MSNs expressing channelrhodopsin 2 (ChR2). Subsequent structural alterations which induced long-term activity changes in these MSNs were investigated in the striatal pathway and its associated regions by diffusion tensor imaging (DTI) and histological assessment with super-resolution microscopy. DTI detected changes in the striatum, substantia nigra, and motor cortex. Histological assessment found a reduction in the diameter of myelinated cortical axons as well as MSN dendrites and axons. The structural changes showed a high correlation between DTI parameters and histological data. These results demonstrated that long-term neural activation in the MSNs alters the diameter of MSN and cortical neurons fibers. This study provides a tool for understanding the causal relationship between functional and structural alterations.",
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AU - Okano, Hideyuki

AU - Tanaka, Kenji

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