Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars reticulata in vitro

Research output: Contribution to journalArticle

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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. Using the 'blind' whole-cell patch clamp recording technique in rat brain slices, we found that focal electrical stimulation of the STN evoked complex, long-duration excitatory postsynaptic currents (EPSCs) 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 (2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitro-quinoxalone) 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 antagonists picrotoxin or bicuculline. These data suggest that recurrent glutamate synapses in the STN generate polysynaptic, complex EPSCs that are under tonic inhibition by GABA. Because complex EPSCs are expected to generate bursts of action potentials in SNR neurons, we suggest that complex EPSCs may contribute to the pathological burst firing that is associated with the symptoms of Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)697-709
Number of pages13
JournalJournal of Physiology
Volume573
Issue number3
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

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Excitatory Postsynaptic Potentials
Subthalamic Nucleus
Neurons
Parkinson Disease
In Vitro Techniques
Pars Reticulata
GABA-A Receptor Agonists
2-Amino-5-phosphonovalerate
Ionotropic Glutamate Receptors
GABA-A Receptor Antagonists
Picrotoxin
Excitatory Amino Acid Antagonists
Bicuculline
Patch-Clamp Techniques
Basal Ganglia
Baths
Synapses
gamma-Aminobutyric Acid
Electric Stimulation
Action Potentials

ASJC Scopus subject areas

  • Physiology

Cite this

Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars reticulata in vitro. / Shen, Ke-Zhong; Johnson, Steven.

In: Journal of Physiology, Vol. 573, No. 3, 15.06.2006, p. 697-709.

Research output: Contribution to journalArticle

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