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Publication : Loss of Striatonigral GABAergic Presynaptic Inhibition Enables Motor Sensitization in Parkinsonian Mice.

First Author  Borgkvist A Year  2015
Journal  Neuron Volume  87
Issue  5 Pages  976-88
PubMed ID  26335644 Mgi Jnum  J:255121
Mgi Id  MGI:6109961 Doi  10.1016/j.neuron.2015.08.022
Citation  Borgkvist A, et al. (2015) Loss of Striatonigral GABAergic Presynaptic Inhibition Enables Motor Sensitization in Parkinsonian Mice. Neuron 87(5):976-88
abstractText  Degeneration of dopamine (DA) neurons in Parkinson''s disease (PD) causes hypokinesia, but DA replacement therapy can elicit exaggerated voluntary and involuntary behaviors that have been attributed to enhanced DA receptor sensitivity in striatal projection neurons. Here we reveal that in hemiparkinsonian mice, striatal D1 receptor-expressing medium spiny neurons (MSNs) directly projecting to the substantia nigra reticulata (SNr) lose tonic presynaptic inhibition by GABAB receptors. The absence of presynaptic GABAB response potentiates evoked GABA release from MSN efferents to the SNr and drives motor sensitization. This alternative mechanism of sensitization suggests a synaptic target for PD pharmacotherapy.
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