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


ABSTRACT: 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.

SUBMITTER: Borgkvist A 

PROVIDER: S-EPMC4559856 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Borgkvist Anders A   Avegno Elizabeth M EM   Wong Minerva Y MY   Kheirbek Mazen A MA   Sonders Mark S MS   Hen Rene R   Sulzer David D  

Neuron 20150901 5


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 o  ...[more]

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