Relationship between subthalamic nucleus neuronal activity and electrocorticogram is altered in the R6/2 mouse model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder in which impairments in the processing of information between the cortex and basal ganglia are fundamental to the onset and progression of the HD phenotype. The corticosubthalamic hyperdirect pathway plays a pivotal role in motor selection and blockade of neuronal activity in the subthalamic nucleus (STN) results in a hyperkinetic movement syndrome, similar to the HD phenotype. The aim of the present study was to examine the relationship between neuronal activity in the STN and cortex in an animal model of HD. We performed in vivo extracellular recordings in the STN to measure single-unit activity and local field potentials in the R6/2 transgenic mouse model of HD. These recordings were obtained during epochs of simultaneously acquired electrocorticogram (ECoG) in discrete brain states representative of global cortical network synchronization or desynchronization. Cortically patterned STN neuronal activity was less phase-locked in R6/2 mice, which is likely to result in less efficient coding of cortical inputs by the basal ganglia. In R6/2 mice, the power of the ECoG in lower frequencies (0.5-4Hz) was diminished while the power expressed in higher frequencies (13-100Hz) was increased. In addition, the spontaneous activity of STN neurons in R6/2 mice was reduced and neurons exhibited a more irregular firing pattern. Glutamatergic STN neurons provide the major excitatory drive to the output nuclei of the basal ganglia and altered discharge patterns could lead to aberrant basal ganglia output and disordered motor control in HD.