title: Impaired plasticity at specific subset of striatal synapses in the Ts65Dn mouse model of Down syndrome.
abstract: BACKGROUND
  Trisomy 21 or Down syndrome (DS) is the most frequent genetic cause of mental retardation. There is limited insight into the biological basis for the cognitive and motor deficits in DS. Because the striatum plays a key role in the regulation and learning of voluntary movements and in cognitive processes, our study was aimed at investigating striatal synaptic transmission and plasticity in a well-accepted genetic model of DS.
  
  
  METHODS
  Electrophysiological recordings were performed in a corticostriatal slice preparation from trisomic (Ts65Dn) and wild-type mice. Synaptic properties and plasticity, long-term potentiation (LTP) and long-term depression (LTD), were investigated.
  
  
  RESULTS
  The basal electrophysiological properties of striatal principal spiny neurons and cholinergic interneurons were spared in the Ts65Dn mouse model of DS. Striatal principal spiny neurons from Ts65Dn mice maintained their ability to undergo LTP and LTD. Conversely, LTP was lost in striatal cholinergic interneurons of Ts65Dn mice. The loss of LTP in striatal cholinergic interneurons of Ts65Dn mice was accompanied by a severe impairment of endogenous cholinergic signaling within the striatum.
  
  
  CONCLUSIONS
  The intrastriatal cholinergic system that was thought to be spared in DS is functionally altered in the Ts65Dn genetic model of DS. Altered cholinergic transmission might play a critical role in the pathophysiology of motor and cognitive deficits in DS, leading to an abnormal processing of neuronal inputs within the basal ganglia. Targeting striatal cholinergic transmission might represent a new therapeutic strategy in DS.
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Via S. Andrea delle Fratte, 06156 Perugia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Filippo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tozzi
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Costa
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cipriani
authors.forename: Michela
authors.initials: M
authors.lastname: Tantucci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Belcastro
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D002800:Cholinesterase Inhibitors; D009388:Neostigmine