Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models

Hongyu Zhang (), Chunlei Zhang, Jean Vincent, Diana Zala, Caroline Benstaali, Matthieu Sainlos, Dolors Grillo-Bosch, Sophie Daburon, Françoise Coussen, Yoon Cho, Denis J. David, Frederic Saudou (), Yann Humeau and Daniel Choquet ()
Additional contact information
Hongyu Zhang: University of Bordeaux
Chunlei Zhang: University of Bordeaux
Jean Vincent: University of Bordeaux
Diana Zala: CNRS, UMR3306, Inserm, U1005
Caroline Benstaali: Grenoble Institut des Neurosciences, GIN
Matthieu Sainlos: University of Bordeaux
Dolors Grillo-Bosch: University of Bordeaux
Sophie Daburon: University of Bordeaux
Françoise Coussen: University of Bordeaux
Yoon Cho: University of Bordeaux
Denis J. David: CESP, INSERM UMRS1178
Frederic Saudou: Grenoble Institut des Neurosciences, GIN
Yann Humeau: University of Bordeaux
Daniel Choquet: University of Bordeaux

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Impaired hippocampal synaptic plasticity contributes to cognitive impairment in Huntington’s disease (HD). However, the molecular basis of such synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that AMPAR surface diffusion, a key player in synaptic plasticity, is disturbed in various rodent models of HD. We demonstrate that defects in the brain-derived neurotrophic factor (BDNF)–tyrosine receptor kinase B (TrkB) signaling pathway contribute to the deregulated AMPAR trafficking by reducing the interaction between transmembrane AMPA receptor regulatory proteins (TARPs) and the PDZ-domain scaffold protein PSD95. The disturbed AMPAR surface diffusion is rescued by the antidepressant drug tianeptine via the BDNF signaling pathway. Tianeptine also restores the impaired LTP and hippocampus-dependent memory in different HD mouse models. These findings unravel a mechanism underlying hippocampal synaptic and memory dysfunction in HD, and highlight AMPAR surface diffusion as a promising therapeutic target.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06675-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06675-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06675-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().