| Title | Dopamine-deprived striatal GABAergic interneurons burst and generate repetitive gigantic IPSCs in medium spiny neurons. | | Author(s) | Dehorter N, Guigoni C, Lopez C, Hirsch J, Eusebio A, Ben-Ari Y, Hammond C | | Institution | Institut de Neurobiologie de Méditerranée Unité Mixte de Recherche 901, Inserm and Aix Marseille II University, 13009 Marseille, France. | | Source | J Neurosci 2009 Jun 17; 29(24):7776-87. | | MeSH | 6-Cyano-7-nitroquinoxaline-2,3-dione
Action Potentials
Adrenergic Agents
Animals
Biological Clocks
Biophysics
Corpus Striatum
Dopamine
Dose-Response Relationship, Drug
Electric Stimulation
Excitatory Amino Acid Antagonists
GABA Agents
Inhibitory Postsynaptic Potentials
Interneurons
Lysine
Mice
Nicotine
Nicotinic Agonists
Oxidopamine
Patch-Clamp Techniques
Spectrum Analysis
Tyrosine 3-Monooxygenase
Valine
gamma-Aminobutyric Acid
| | Abstract | Striatal GABAergic microcircuits modulate cortical responses and movement execution in part by controlling the activity of medium spiny neurons (MSNs). How this is altered by chronic dopamine depletion, such as in Parkinson's disease, is not presently understood. We now report that, in dopamine-depleted slices of the striatum, MSNs generate giant spontaneous postsynaptic GABAergic currents (single or in bursts at 60 Hz) interspersed with silent episodes, rather than the continuous, low-frequency GABAergic drive (5 Hz) observed in control MSNs. This shift was observed in one-half of the MSN population, including both "D(1)-negative" and "D(1)-positive" MSNs. Single GABA and NMDA channel recordings revealed that the resting membrane potential and reversal potential of GABA were similar in control and dopamine-depleted MSNs, and depolarizing, but not excitatory, actions of GABA were observed. Glutamatergic and cholinergic antagonists did not block the GABAergic oscillations, suggesting that they were generated by GABAergic neurons. In support of this, cell-attached recordings revealed that a subpopulation of intrastriatal GABAergic interneurons generated bursts of spikes in dopamine-deprived conditions. This subpopulation included low-threshold spike interneurons but not fast-spiking interneurons, cholinergic interneurons, or MSNs. Therefore, a population of local GABAergic interneurons shifts from tonic to oscillatory mode when dopamine deprived and gives rise to spontaneous repetitive giant GABAergic currents in one-half the MSNs. We suggest that this may in turn alter integration of cortical signals by MSNs. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19535589 |
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