Neuron
Volume 71, Issue 5, 8 September 2011, Pages 858-868
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Article
Rapid Target-Specific Remodeling of Fast-Spiking Inhibitory Circuits after Loss of Dopamine

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Summary

In Parkinson's disease (PD), dopamine depletion alters neuronal activity in the direct and indirect pathways and leads to increased synchrony in the basal ganglia network. However, the origins of these changes remain elusive. Because GABAergic interneurons regulate activity of projection neurons and promote neuronal synchrony, we recorded from pairs of striatal fast-spiking (FS) interneurons and direct- or indirect-pathway MSNs after dopamine depletion with 6-OHDA. Synaptic properties of FS-MSN connections remained similar, yet within 3 days of dopamine depletion, individual FS cells doubled their connectivity to indirect-pathway MSNs, whereas connections to direct-pathway MSNs remained unchanged. A model of the striatal microcircuit revealed that such increases in FS innervation were effective at enhancing synchrony within targeted cell populations. These data suggest that after dopamine depletion, rapid target-specific microcircuit organization in the striatum may lead to increased synchrony of indirect-pathway MSNs that contributes to pathological network oscillations and motor symptoms of PD.

Highlights

► Dopamine depletion induces axonal remodeling in striatal fast-spiking interneurons ► New synapses are formed selectively in striatal indirect-pathway projection neurons ► Enhanced inhibition of D2 MSNs is predicted to increase firing synchrony ► Remodeling of striatal microcircuitry may induce pathological synchrony in PD

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