Extrastriatal plasticity in parkinsonism

Abstract

Two new rodent brain slice recording studies (Miguelez et al. [1] and Fan et al. [2]) suggest that chronic dopamine loss in parkinsonism not only affects synaptic plasticity in the striatum, but also results in functional and morphological changes in other basal ganglia nuclei, specifically the globus pallidus (GP) and the subthalamic nucleus (STN). With a series of electrophysiological and optogenetic experiments, Miguelez et al. showed that the short term plasticity of striato-pallidal GABAergic synapses and pallido-pallidal GABAergic synapses differ such that their synaptic properties change in opposite directions in response to striatal activation, even under normal conditions. Studies in dopamine-depleted animals suggest that chronic dopamine loss selectively fosters plasticity at pallido-pallidal synapses. This may lead to rebound bursting, and to the development of synchronized firing patterns that are known to be associated with parkinsonism. The article by Fan et al. highlights the plastic properties of another extrastriatal synapse within the ‘indirect’ pathway of the basal ganglia, i.e., the pallido-subthalamic connection, with the surprising result that dopamine depletion may affect pallido-subthalamic transmission through synaptic mechanisms that rely on morphological and pharmacological changes of the GABAergic pallido-subthalamic synapses. Both studies substantially expand our knowledge of the extrastriatal effects of dopamine, and demonstrate that the plastic properties of extrastriatal synaptic networks in the basal ganglia may contribute to the complex physiological changes that occur in response to the seemingly simple biochemical insult of dopamine loss. Future studies are warranted to assess the pathologic or compensatory nature of these plastic events in parkinsonism.