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

Cristina Miguelez, Stéphanie Morin, Audrey Martinez, Michel Goillandeau, Erwan Bezard, Bernard Bioulac, Jérôme Baufreton
The Journal of Physiology. 2012-09-25; 590(22): 5861-5875
DOI: 10.1113/jphysiol.2012.241331

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1. 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.

Miguelez C(1), Morin S, Martinez A, Goillandeau M, Bezard E, Bioulac B, Baufreton
J.

Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodegeneratives, UMR 5293, F-33000
Bordeaux, France.

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.

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


Auteurs Bordeaux Neurocampus