S. ZHONG , H. LIN, A. GHAVAMI, F.R. POSTMA, R. ROGERS, R.CACHOPE, V.BEAUMONT
Huntington’s disease (HD) is a lethal autosomal dominant neurodegenerative disorder caused by expansion of CAG repeats in the Huntingtin (HTT) gene. HD patient brains reveal a devastation of the caudate-putamen and cortico-striatalthalamo-cortical circuits are thought to be particularly affected. Choreic symptoms correlate well with D2-containing medium spiny neuron (MSN) loss, which originate the indirect pathway. MSN dysfunction has been extensively studied in-vitro in models of HD, but the functional consequences on the immediate downstream nuclei of the indirect pathway, the external Globus Pallidus and subthalamic nucleus (STN), remains unknown. Here we characterized a basal ganglia circuitry dysfunction relevant to the human HD condition. These functional in-vivo assays will allow for the assessment of novel compounds with potential disease modifying properties.