Altered pallido-pallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease
Article first published online: 25 SEP 2012
© 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society
The Journal of Physiology
Volume 590, Issue 22, pages 5861–5875, November 2012
How to Cite
Miguelez, C., Morin, S., Martinez, A., Goillandeau, M., Bezard, E., Bioulac, B. and Baufreton, J. (2012), Altered pallido-pallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease. The Journal of Physiology, 590: 5861–5875. doi: 10.1113/jphysiol.2012.241331
- Issue published online: 20 NOV 2012
- Article first published online: 25 SEP 2012
- Accepted manuscript online: 22 AUG 2012 11:10AM EST
- (Resubmitted 20 July 2012; accepted 10 August 2012; first published online 13 August 2012)
- • We used optogenetics approach to characterize the short-term plasticity of striato-pallidal (STR–GP) and pallido-pallidal (GP–GP) GABAergic synapses in rat brain slices.
- • We show that only GP–GP (and not STR–GP) transmission is augmented by chronic dopamine depletion.
- • Finally, we report that altered GP–GP synaptic transmission promotes neuronal synchronization and rebound bursting in globus pallidus neurons.
- • Our results support the conclusion that maladaptive GP–GP GABAergic transmission is likely to be a key underlying factor of the pathological activity in the globus pallidus observed in Parkinson's disease.
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 D2 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.