Dataset Information

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

ABSTRACT:

Background

Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored.

Methods

We used two different mouse models of HD, the R6/1 and the HdhQ111 mice, to demonstrate a consistent thalamic Foxp2 reduction in the context of HD. We used in vivo electrophysiological recordings, microdialysis in behaving mice and rabies virus-based monosynaptic tracing to study thalamo-striatal and thalamo-cortical synaptic connectivity in R6/1 mice. Micro-structural synaptic plasticity was also evaluated in the striatum and cortex of R6/1 mice. We over-expressed Foxp2 in the thalamus of R6/1 mice or reduced Foxp2 in the thalamus of wild type mice to evaluate its role in sensory and motor skills deficiencies, as well as thalamo-striatal and thalamo-cortical connectivity in such mouse models.

Results

Here, we demonstrate in a HD mouse model a clear and early thalamo-striatal aberrant connectivity associated with a reduction of thalamic Foxp2 levels. Recovering thalamic Foxp2 levels in the mouse rescued motor coordination and sensory skills concomitant with an amelioration of neuropathological features and with a repair of the structural and functional connectivity through a restoration of neurotransmitter release. In addition, reduction of thalamic Foxp2 levels in wild type mice induced HD-like phenotypes.

Conclusions

In conclusion, we show that a novel identified thalamic Foxp2 dysregulation alters basal ganglia circuits implicated in the pathophysiology of HD.

SUBMITTER: Rodriguez-Urgelles E

PROVIDER: S-EPMC10663254 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

Rodríguez-Urgellés Ened E Casas-Torremocha Diana D Sancho-Balsells Anna A Ballasch Iván I García-García Esther E Miquel-Rio Lluis L Manasanch Arnau A Del Castillo Ignacio I Chen Wanqi W Pupak Anika A Brito Veronica V Tornero Daniel D Rodríguez Manuel J MJ Bortolozzi Analia A Sanchez-Vives Maria V MV Giralt Albert A Alberch Jordi J

Cellular and molecular life sciences : CMLS 20231121 12

<h4>Background</h4>Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored.<h4>Methods</h4>We used two different mouse models of HD, the R6/1 and the H ...[more]

PMID: 37987826

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Dataset Information

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

Background

Methods

Results

Conclusions

Publications

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

Similar Datasets

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