Giant GABA_A receptor mediated currents in the striatum, a common signature of Parkinson's disease in pharmacological and genetic rodent models

Oscillatory giant GABA_A receptor-mediated currents recorded from medium spiny neurons (MSNs) of the striatum in vitro are an electrophysiological signature of dysfunctioning dopaminergic synaptic transmission. This is a common early signature of Parkinson's disease in pharmacological and genetic mice models. Recorded from at least 40% of MSNs, these currents are present both after and up to 10 months before motor signs, and are suppressed by chronic levodopa treatment or chronic lesion of the subthalamic nucleus. Giant GABA_A receptor-mediated currents may result from the diverse changes in the GABAergic striatal circuitry identified after dysfunction in dopaminergic transmission. Fast spiking (FS) interneurons are more strongly electrically coupled and a subpopulation of FS interneurons sprouts onto D2-type MSNs. On the other hand, low threshold spiking (LTS) interneurons shift to an excessive and recurrent bursting pattern. All these effects are likely to lead to profound dysfunction in the striatal GABAergic network, given that MSN responses to cortical inputs are highly dependent on GABAergic inputs and that GABAergic interneurons play a fundamental role in network oscillations.