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S.W. Johnson "Reverberating circuits in the basal ganglia: a focus on the subthalamonigral pathway"

Abstract :

The subthalamic nucleus (STN) plays an important role in movement control by exerting its excitatory influence on the substantia nigra pars reticulata (SNR), a major output structure of the basal ganglia.
Moreover, excessive burst firing of SNR neurons seen in Parkinson’s disease has been attributed to excessive transmission in the subthalamonigral pathway. In this seminar, I will report results of recent studies from our laboratory in which we used the whole-cell patch clamp recording technique in rat brain slices to characterize synaptic transmission in the subthalamonigral pathway. We found that focal electrical stimulation of the STN evoked complex, long-duration excitatory postsynaptic currents (EPSCs) in SNR neurons. When recorded under current clamp conditions, the complex excitatory postsynaptic potentials trigger bursts of action potentials in SNR neurons. Complex EPSCs lasted 200 – 500 ms and consisted of an initial monosynaptic EPSC followed by a series of late EPSCs superimposed on a slow inward shift in holding current. Focal stimulation of regions outside the STN failed to evoke complex EPSCs. The late component of complex EPSCs was markedly reduced by ionotropic glutamate receptor antagonists and by a GABAA receptor agonist (isoguvacine) when these agents were applied directly to the STN using a fast-flow microapplicator. Moreover, the complex EPSC was greatly enhanced by bath application of the GABAA receptor antagonist picrotoxin or bicuculline. These data suggest that recurrent glutamate synapses in the STN generate polysynaptic, complex EPSCs that are under tonic inhibition by GABA. Our data also provides evidence of reverberating excitatory connections within the STN. Because complex EPSCs are expected to generate bursts of action potentials in SNR neurons, we suggest that complex EPSCs may contribute to pathological burst firing that is associated with symptoms of Parkinson’s disease. 

Selected publications

Shen K-Z and Johnson SW (2006) Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars reticulata in vitro.
J Physiol (in press).
Zhu Z-T, Munhall A, Shen K-Z and Johnson SW (2005) NMDA enhances a depolarization-activated inward current in subthalamic neurons.
Neuropharmacol 49:317-327.
Shen K-Z and Johnson SW (2005) Dopamine depletion alters responses to glutamate and GABA in the rat subthalamic nucleus. NeuroReport 16:171-174.
Johnson SW and Wu Y-N (2004) Multiple mechanisms underlie burst firing in rat midbrain dopamine neurons in vitro. Brain Res 1019:293-296.

Zhu Z-T, Munhall A, Shen K-Z and Johnson SW (2004) Calcium dependent subthreshold oscillations determine bursting activity induced by N-methyl-D-aspartate in rat subthalamic neurons in vitro.
Eur J Neurosci 19:1296-1304. 

Anne Taupignon