TY - JOUR
T1 - 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
PY - 2018/3/5
Y1 - 2018/3/5
N2 - 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.
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+/∆ 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.
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U2 - 10.7554/eLife.33331
DO - 10.7554/eLife.33331
M3 - Article
AN - SCOPUS:85045638976
VL - 7
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e33331
ER -