- 作者：Massimiliano Di Filippo ; Aless ; ro Tozzi ; Veronica Ghiglieri ; Barbara Picconi ; Cinzia Costa ; Sabrina Cipriani ; Michela Tantucci ; Vincenzo Belcastro ; Paolo Calabresi
- 关键词：Cholinergic interneurons ; Down syndrome ; long-term depression ; long-term potentiation ; striatum ; Ts65Dn
- 刊名：Biological Psychiatry
- 出版年：2010
- 出版时间：1 April 2010
- 年：2010
- 卷：67
- 期：7
- 页码：666-671
- 全文大小：1105 K
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.