Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29504938.
- Also identified by DOI 10.7554/eLife.33331 and PMC identifier 5849413.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Tor1a</i><sup>+/Δgag</sup> 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 <i>Tor1a</i><sup>+/Δgag</sup> 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 <i>Tor1a</i><sup>+/Δgag</sup> 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.
Medical subject headings
- Corpus Striatum
- Dystonia
- Molecular Chaperones
- Neuronal Plasticity