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Parkinson’s disease is characterized by the progressive loss of midbrain dopamine neurons. Dopamine replacement therapy with levodopa alleviates parkinsonian motor symptoms but is complicated by the development of involuntary movements, termed levodopa-induced dyskinesia (LID). Aberrant activity in the striatum has been hypothesized to cause LID. Here, to establish a direct link between striatal activity...
In this issue of Neuron, Shen et al. (2015) demonstrate that the M4 muscarinic receptor regulates striatal plasticity. The authors use an M4-positive allosteric modulator, which facilitates long-term depression in direct pathway neurons and reverses aberrant plasticity in levodopa-induced dyskinesia.
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