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

Neuron
Anders BorgkvistDavid Sulzer

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.

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Citations

Jul 9, 2016·Progress in Neurobiology·Philippe De DeurwaerdèreMark J Millan
Aug 18, 2016·Clinical Neuropharmacology·Nabil El AyoubiRaja Sawaya
Mar 4, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Xiomara A PerezMaryka Quik
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Sep 27, 2018·Journal of Neurophysiology·Verónica Alejandra Cáceres-ChávezJosé Bargas
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Jun 1, 2021·Frontiers in Aging Neuroscience·Haruo NishijimaMasahiko Tomiyama
May 29, 2021·Neuroscience·Rodrigo Manuel Paz, Mario Gustavo Murer

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