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Current Opinions and Consensus for Studying Tremor in Animal Models

  • Consensus Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Tremor is the most common movement disorder; however, we are just beginning to understand the brain circuitry that generates tremor. Various neuroimaging, neuropathological, and physiological studies in human tremor disorders have been performed to further our knowledge of tremor. But, the causal relationship between these observations and tremor is usually difficult to establish and detailed mechanisms are not sufficiently studied. To overcome these obstacles, animal models can provide an important means to look into human tremor disorders. In this manuscript, we will discuss the use of different species of animals (mice, rats, fruit flies, pigs, and monkeys) to model human tremor disorders. Several ways to manipulate the brain circuitry and physiology in these animal models (pharmacology, genetics, and lesioning) will also be discussed. Finally, we will discuss how these animal models can help us to gain knowledge of the pathophysiology of human tremor disorders, which could serve as a platform towards developing novel therapies for tremor.

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Abbreviations

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CF:

Climbing fiber

CS:

Complex spike

CV:

Coefficient of variation

DCN:

Deep cerebellar nucleus

EEG:

Electroencephalogram

ET:

Essential tremor

fMRI:

Functional magnetic resonance imaging

KO:

Knockout

GABAAR:

GABAA receptor

HCN channel:

Hyperpolarization-activated cyclic nucleotide-gated channel

IO:

Inferior olive

ISI:

Inter-spike interval

MES:

Maximal electroshock seizure

NMDA:

N-methyl-d-aspartate

PC:

Purkinje cells

pcd :

Purkinje cell degeneration

PD:

Parkinson disease

PET:

Positron emission tomography

SCA:

Spinocerebellar ataxia

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Funding

Sheng-Han Kuo has received funding from the National Institutes of Health, NINDS #R01 NS104423 (principal investigator) NINDS #K08 NS083738 (principal investigator), and the Louis V. Gerstner Jr. Scholar Award, Parkinson’s Foundation, and International Essential Tremor Foundation. Elan D. Louis has received research support from the National Institutes of Health: NINDS #R01 NS094607 (principal investigator), NINDS #R01 NS085136 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator), and NINDS #R01 NS088257 (principal investigator). He has also received support from the Claire O’Neil Essential Tremor Research Fund (Yale University). Phyllis L. Faust has received funding from the National Institutes of Health: NINDS #R01 NS088257 (principal investigator) and NINDS #R01 NS085136 (principal investigator). Adrian Handforth has received support from Veterans Affairs and the International Essential Tremor Foundation. Su-youne Chang has received NINDS #R01 NS088260 (principal investigator). Ming-Kai Pan has received research support from Ministry of Science and Technology in Taiwan: MOST #104-2314-B-002-076-MY3 and 107-2321-B-002-020 (principal investigator). Eric J. Lang has received funding from the National Institutes of Health: NINDS #R21 NS101386 (principal investigator). Stefan M. Pulst has received funding from the National Institutes of Health: NINDS #R37 NS033123 (principal investigator), NINDS #R01 NS097903 (principal investigator), NINDS #U01 NS103883 (principal investigator), NINDS #R21 NS103009 (principal investigator), NINDS #R21 NS104799 (principal investigator), NINDS #R21 NS079852 (principal investigator), and Utah Neuroscience Initiative Collaborative Pilot Project Award. Collin J. Anderson has received funding from National Ataxia Foundation Postdoc Fellowship. Roy V. Sillitoe has received funds from BCM IDDRC grant U54HD083092 (Neurovisualization Core), the National Institutes of Health NINDS #R01NS089664 (principal investigator) and #R01NS100874 (principal investigator), and the Hamill Foundation. Amanda M. Brown is supported by the National Institutes of Health NINDS #F31 NS101891. Dane M. Chetkovich is supported by the National Institutes of Health NINDS #R01NS059934 (principal investigator), NIMH #R01MH106511 (principal investigator), and NIMH #R21MH113262 (principal investigator). Lorriane Clark recieves support from the National Institutes of Health NINDS #R01 NS073872 (principal investigator) and NINDS #R21 NS0988930 (principal investigator). Rodger J. Elble receives support from the Neuroscience Research Foundation of Kiwanis International Illinois-Eastern Iowa District.

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Authors and Affiliations

  1. Department of Neurology, Columbia University, 650 West 168th Street, Room 305, New York, NY, 10032, USA

    Sheng-Han Kuo

  2. Department of Neurology, Yale School of Medicine, Yale University, 800 Howard Avenue, Ste Lower Level, New Haven, CT, 06519, USA

    Elan D. Louis

  3. Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA

    Elan D. Louis

  4. Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA

    Elan D. Louis

  5. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, USA

    Phyllis L. Faust & Lorraine N. Clark

  6. Neurology Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Adrian Handforth

  7. Department of Neurologic Surgery and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA

    Su-youne Chang

  8. Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY, USA

    Billur Avlar & Eric J. Lang

  9. Department of Medical Research and Neurology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Ming-Kai Pan

  10. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    Lauren N. Miterko, Amanda M. Brown & Roy V. Sillitoe

  11. Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA

    Lauren N. Miterko & Roy V. Sillitoe

  12. Jan and Dan Duncan Neurological Research Institute of Texas Children’s Hospital, Houston, TX, USA

    Lauren N. Miterko, Amanda M. Brown & Roy V. Sillitoe

  13. Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA

    Amanda M. Brown & Roy V. Sillitoe

  14. Department of Neurology, University of Utah, Salt Lake City, UT, USA

    Collin J. Anderson & Stefan M. Pulst

  15. Department of Neurology, Vanderbilt University, Nashville, TN, USA

    Martin J. Gallagher & Dane M. Chetkovich

  16. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Kyle A. Lyman

  17. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Lorraine N. Clark

  18. Department of Neurology, National Neuroscience Institute, Singapore, Singapore

    Murni Tio & Eng-King Tan

  19. Duke-NUS Graduate Medical School, Singapore, Singapore

    Murni Tio & Eng-King Tan

  20. Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA

    Rodger J. Elble

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  1. Sheng-Han Kuo
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  2. Elan D. Louis
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Correspondence to Sheng-Han Kuo or Elan D. Louis.

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Kuo, SH., Louis, E.D., Faust, P.L. et al. Current Opinions and Consensus for Studying Tremor in Animal Models. Cerebellum 18, 1036–1063 (2019). https://doi.org/10.1007/s12311-019-01037-1

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