Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

Marta Maltese, Jennifer Stanic, Annalisa Tassone, Giuseppe Sciamanna, Giulia Ponterio, Valentina Vanni, Giuseppina Martella, Paola Imbriani, Paola Bonsi, Nicola Biagio Mercuri, Fabrizio Gardoni, Antonio Pisani

Research output: Contribution to journalArticle

Abstract

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/∆ gag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/∆gag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/∆gag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers.

Original languageEnglish
Article numbere33331
JournaleLife
Volume7
DOIs
Publication statusPublished - Mar 5 2018

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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