| First Author | Kung VW | Year | 2007 |
| Journal | Neuroscience | Volume | 146 |
| Issue | 4 | Pages | 1571-80 |
| PubMed ID | 17478055 | Mgi Jnum | J:122067 |
| Mgi Id | MGI:3713136 | Doi | 10.1016/j.neuroscience.2007.03.036 |
| Citation | Kung VW, et al. (2007) Dopamine-dependent long term potentiation in the dorsal striatum is reduced in the R6/2 mouse model of Huntington's disease. Neuroscience 146(4):1571-80 |
| abstractText | The striatum is critically important in motor, cognitive and emotional functions, as highlighted in neurological disorders such as Huntington's disease (HD) where these functions are compromised. The R6/2 mouse model of HD shows progressive motor and cognitive impairments and alterations in striatal dopamine and glutamate release. To determine whether or not dopamine-dependent neuronal plasticity is also altered in the dorsolateral striatum of R6/2 mice, we compared long term potentiation (LTP) and long term depression (LTD) in striatal slices from R6/2 mice with that seen in slices from wild type (WT) mice. In adult WT mice (aged 8-19 weeks), frequency-dependent bidirectional plasticity was observed. High frequency stimulation (four 0.5 s trains at 100 Hz, inter-train interval 10 s) induced LTP (134+/-5% of baseline), while low frequency stimulation (4 Hz for 15 min) induced LTD (80+/-5% of baseline). LTP and LTD were significantly blocked by the N-methyl-d-aspartic acid (NMDA) receptor antagonist d(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (to 93+/-6% and 103+/-8% of baseline respectively), indicating that they are both dependent on NMDA glutamate receptor activation. LTP was significantly blocked by the dopamine D(1) receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazep ine hydrochloride (SCH-23390) (98+/-8% of baseline), indicating that LTP is dependent on activation of dopamine D(1)-type receptors, whereas LTD was not significantly different (90+/-7%). In adult R6/2 mice (aged 8-19 weeks), LTP was significantly reduced (to 110+/-4% of baseline), while LTD was not significantly different from that seen in WT mice (85+/-6%). These data show that R6/2 mice have impaired dopamine-dependent neuronal plasticity in the striatum. As dopamine-dependent plasticity is a proposed model of striatum-based motor and cognitive functions, this impairment could contribute to deficits seen in R6/2 mice. |
