Parkin deficiency perturbs striatal circuit dynamics
Loss-of-function mutations in the parkin-encoding PARK2 gene cause young-onset, autosomal recessive Parkinsons disease (PD). Here, we investigated how parkin mutations affect cortico-basal ganglia circuit dynamics and cell-type-specific functional connectivity by recording simultaneously from motor cortex, striatum and globus pallidus (GP) in anesthetized parkin-mutant mice.\n\nWhile ongoing activity of presumed striatal spiny projection neurons and their downstream counterparts in the GP was not different from controls, parkin deficiency had a differential impact on striatal interneurons: In parkin-mutant mice, tonically active neurons displayed elevated activity levels. Baseline firing of transgenic striatal fast spiking interneurons (FSI), on the contrary, was reduced and the correlational structure of the FSI microcircuitry was disrupted. The entire transgenic striatal microcircuit showed enhanced and phase-shifted phase coupling to slow (1-3Hz) cortical population oscillations. Unexpectedly, local field potentials recorded from striatum and GP of parkin-mutant mice robustly displayed amplified beta oscillations ([~]22Hz), phase-coupled to cortex. Moreover, parkin deficiency selectively increased spike-field coupling of FSIs to beta oscillations.\n\nOur findings suggest that loss of parkin function leads to amplifications of synchronized cortico-striatal oscillations and intrastriatal reconfiguration of interneuronal circuits. This presymptomatic disarrangement of dynamic functional connectivity may precede nigro-striatal neurodegeneration and predispose to imbalance of striatal outflow accompanying symptomatic PD.