1. Neuroscience

Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia

  1. Hind Baba Aïssa
  2. Romain W Sala
  3. Elena Laura Georgescu Margarint
  4. Jimena Laura Frontera
  5. Andrés Pablo Varani
  6. Fabien Menardy
  7. Assunta Pelosi
  8. Denis Hervé
  9. Clément Léna  Is a corresponding author
  10. Daniela Popa  Is a corresponding author
  1. Neurophysiology of Brain Circuits Team, Institut de biologie de l'Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, France
  2. Inserm UMR-S 1270, France
  3. Sorbonne Université, Sciences and Technology Faculty, France
  4. Institut du Fer à Moulin, France
https://doi.org/10.7554/eLife.79135
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Cite this article
  1. Hind Baba Aïssa
  2. Romain W Sala
  3. Elena Laura Georgescu Margarint
  4. Jimena Laura Frontera
  5. Andrés Pablo Varani
  6. Fabien Menardy
  7. Assunta Pelosi
  8. Denis Hervé
  9. Clément Léna
  10. Daniela Popa
(2022)
Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia
eLife 11:e79135.
https://doi.org/10.7554/eLife.79135
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5 figures and 2 additional files

Figures

Figure 1
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Young male and female Gnal+/- mice do not display motor coordination impairments.

(A) Latency to climb down the vertical pole in male and female Gnal+/- (GNAL) and wildtype (WT) mice. (B) Latency to cross the horizontal bar. (C) Latency to fall during the grid test (30 s cutoff). …

Figure 2 with 3 supplements
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Exposure to oxotremorine causes a long-lasting increase in thalamic and cortical response to dentate nucleus (DN) stimulation in Gnal+/- mice.

(A) Schematics describing the experimental design of thalamo-cortical recordings coupled with DN stimulation (top) and experimental timeline (bottom). (B) Examples of peristimulus time histogram …

Figure 2—figure supplement 1
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Electrophysiology recordings in thalamo-cortical and cerebello-striatal networks.

(A) Picture of a freely moving mouse during a recording coupled with optogenetic DN stimulation. (B) Schematics describing the experimental design of thalamo-cortical recordings coupled with DN …

Figure 2—figure supplement 2
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Effects of initial exposure to oxotremorine and dentate nucleus (DN) stimulation on the thalamo-cortical network in wildtype (WT) and Gnal+/- mice.

(A) Comparison of mean firing rate under saline and oxotremorine conditions in ventrolateral thalamus (VAL), centrolateral thalamus (CL), and primary motor cortex (M1). *p<0.05, **p<0.01, ***p<0.001 …

Figure 2—figure supplement 3
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Effects of initial exposure to oxotremorine on the regularity of thalamic firing patterns in wildtype (WT) and Gnal+/- mice.

(A) Comparison of CVisi under saline and oxotremorine conditions in ventrolateral thalamus (VAL) and centrolateral thalamus (CL). *p<0.05, **p<0.01, ***p<0.001 paired difference between treatment …

Figure 3
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Asymptomatic Gnal+/- mice display an abnormal cerebello-thalamic plasticity induced by dentate nucleus (DN) θ-bursts.

(A) Schematics describing the experimental design of thalamo-cortical recordings coupled with dentate nucleus-centrolateral thalamus (DN-CL) stimulation (top) and experimental timeline (bottom). All …

Figure 4 with 2 supplements
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Dentate nucleus-centrolateral thalamus (DN-CL) θ-bursts potentiate the response of fast-spiking dorsolateral striatum (DLS) neurons to DN stimulation in WT wildtype (mice), but not in Gnal+/- mice.

(A) Schematics describing the experimental design of cerebello-striatal recordings coupled with DN-CL stimulation (top) and experimental timeline (bottom). (B) Distributions of response amplitude in …

Figure 4—figure supplement 1
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Dentate nucleus-centrolateral thalamus (DN-CL) θ-bursts elicit excitation in DN neurons and dorsolateral striatum (DLS) fast-spiking neurons.

(A) Example high-pass-filtered traces recorded in the DN and DLS during θ-burst, with the corresponding spike-sorted units, showing an increased firing rate induced by θ-burst. θ-burst stimulations …

Figure 4—figure supplement 2
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Effect of oxotremorine on the firing of the dentate nucleus (DN).

(A) Modulation of mean firing rate and (B) CV in the DN caused by oxotremorine administration. Wilcoxon test for paired samples *p<0.05, **p<0.01, ***p<0.001. Mann–Whitney test for independent …

Figure 5
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Dentate nucleus (DN) θ-bursts administered to symptomatic Gnal+/- mice induce a decreased response to DN stimulation and decrease motor symptoms of dystonia.

(A) Schematics describing the experimental design of thalamo-cortical recordings coupled with DN stimulation (top) and experimental timeline (bottom). (B) Distributions of responses to DN …

Additional files

Supplementary file 1

Tables of statistical results for all comparisons reported in the text.

https://cdn.elifesciences.org/articles/79135/elife-79135-supp1-v1.xlsx
MDAR checklist
https://cdn.elifesciences.org/articles/79135/elife-79135-mdarchecklist1-v1.docx

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