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J Physiol. 2012 Nov 15;590(22):5861-75. doi: 10.1113/jphysiol.2012.241331. Epub 2012 Aug 13.

Altered pallido-pallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease.

Author information

1
Univ. de Bordeaux, Institut des Maladies Neurodegeneratives, UMR 5293, F-33000 Bordeaux, France.

Abstract

The pattern of activity of globus pallidus (GP) neurons is tightly regulated by GABAergic inhibition. In addition to extrinsic inputs from the striatum (STR-GP) the other source of GABA to GP neurons arises from intrinsic intranuclear axon collaterals (GP-GP). While the contribution of striatal inputs has been studied, notably its hyperactivity in Parkinson's disease (PD), the properties and function of intranuclear inhibition remain poorly understood. Our objective was therefore to test the impact of chronic dopamine depletion on pallido-pallidal transmission. Using patch-clamp whole-cell recordings in rat brain slices, we combined electrical and optogenetic stimulations with pharmacology to differentiate basic synaptic properties of STR-GP and GP-GP GABAergic synapses. GP-GP synapses were characterized by activity-dependent depression and insensitivity to the D(2) receptor specific agonist quinpirole and STR-GP synapses by frequency-dependent facilitation and quinpirole modulation. Chronic dopamine deprivation obtained in 6-OHDA lesioned animals boosted the amplitude of GP-GP IPSCs but did not modify STR-GP transmission and increased the amplitude of miniature IPSCs. Replacement of calcium by strontium confirmed that the quantal amplitude was increased at GP-GP synapses. Finally, we demonstrated that boosted GP-GP transmission promotes resetting of autonomous activity and rebound-burst firing after dopamine depletion. These results suggest that GP-GP synaptic transmission (but not STR-GP) is augmented by chronic dopamine depletion which could contribute to the aberrant GP neuronal activity observed in PD.

PMID:
22890706
PMCID:
PMC3528996
DOI:
10.1113/jphysiol.2012.241331
[Indexed for MEDLINE]
Free PMC Article

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