Differential Electrophysiological Changes in Striatal Output Neurons in Huntington's Disease

• DOI: 10.1523/jneurosci.3539-10.2011
• Publication Date: 2011-01-27T18:19:30Z
• Authors: Véronique M. André; Carlos Cepeda; Yvette E. Fisher; My Huynh; Nora Bardakjian; Sumedha Singh; X. William Yang; Michael S. Levine
• Keywords: Medium spiny neuron

There is considerable evidence that alterations in striatal medium-sized spiny neurons (MSSNs) giving rise to the direct (D1 receptor-expressing) and indirect (D2 pathways differentially contribute phenotype of Huntington's disease (HD). To determine how each subpopulation MSSN functionally affected, we examined spontaneous excitatory postsynaptic currents (sEPSCs) dopamine (DA) modulation two HD mouse models, YAC128 BACHD (a bacterial-artificial chromosome). These mice also expressed enhanced green fluorescent protein (EGFP) under control promoter for either DA D1 or D2 receptors identify neurons. In early symptomatic mice, glutamate transmission was increased both MSSNs, but different ways. cells displayed sEPSC frequencies decreased paired-pulse ratios (PPRs) while larger evoked no change PPRs. receptor sEPSCs absent D1-YAC128 at stage restored by treating slices with tetrabenazine. contrast, fully specifically cells, normal cells. Behaviorally, showed stereotypies were tetrabenazine treatment. Together, these studies support differential imbalances pathway MSSNs. Stereotypic behavior an could be explained activity tone neurons, whereas hypokinesia later stages result from reduced input onto