Comparison of Normal and Parkinsonian Microcircuit Dynamics in the Rodent Striatum

Abstract

Experimentally, depriving the basal ganglia (BG) from their dopaminergic innervation, dramatically changes the behavior of all their circuits, neurons, and synapses in multiple ways. Dopamine afferents are received by all BG nuclei (Rommelfanger and Wichmann, 2010). In the absence of DA, BG generate enhanced pathological oscillatory patterns in the external segment of the striatum: globus pallidus (GPe), internal segment of the globus pallidus (GPi), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) (Blandini et al., 2000). These pathological oscillatory patterns are expressed as increased cortical beta frequency coherence (Costa et al., 2006; Fuentes et al., 2009; Kozlov et al., 2009; Walters and Bergstrom, 2009) and are reflected as the inability to select, change or initiate motor actions (Magill et al., 2001; Ni et al., 2001; Wilson et al., 2006), as though all neurons were trapped in a massive oscillation that does not allow the selection of any circuit or action. Behaviorally, circuit disfunction is accompanied by bradykinesia, akinesia, tremor and muscular rigidity (Brown, 2007; Hammond et al., 2007; Galvan and Wichmann, 2008; Fuentes et al., 2009; Walters and Bergstrom, 2009; Zold et al., 2009). One question is what are the manifestations of these changes at the level of the striatal microcircuitry (Alexander and Crutcher, 1990; Middleton and Strick, 2002), given that its neurons are the principal entrance to the BG (Alexander and Crutcher, 1990; Middleton and Strick, 2002), and DA is particularly concentrated in this nucleus (striatum); more than in any other BG nuclei (Bjorklund and Dunnett, 2007). To answer this question, here we show how the striatal microcircuit functions before and after DA depletion. The changes observed may be fundamental to understand BG activity during Parkinsonism.