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Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars reticulata in vitro
Author(s) -
Shen KeZhong,
Johnson Steven W.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.110031
Subject(s) - excitatory postsynaptic potential , subthalamic nucleus , neuroscience , glutamatergic , bicuculline , substantia nigra , glutamate receptor , ionotropic effect , stimulation , excitatory amino acid antagonists , bursting , postsynaptic potential , basal ganglia , chemistry , neurotransmission , inhibitory postsynaptic potential , deep brain stimulation , gabaa receptor , biology , parkinson's disease , receptor , medicine , dopamine , central nervous system , biochemistry , disease , dopaminergic
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 GABA A 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 GABA A 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.