TY - JOUR TI - Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum AU - Maltese, Marta AU - Stanic, Jennifer AU - Tassone, Annalisa AU - Sciamanna, Giuseppe AU - Ponterio, Giulia AU - Vanni, Valentina AU - Martella, Giuseppina AU - Imbriani, Paola AU - Bonsi, Paola AU - Mercuri, Nicola Biagio AU - Gardoni, Fabrizio AU - Pisani, Antonio A2 - Rosenmund, Christian VL - 7 PY - 2018 DA - 2018/03/05 SP - e33331 C1 - eLife 2018;7:e33331 DO - 10.7554/eLife.33331 UR - https://doi.org/10.7554/eLife.33331 AB - 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+/Δgag 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+/Δgag 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+/Δgag 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. KW - synaptic plasticity KW - dystonia DYT1 KW - BDNF KW - AMPA receptors JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -