| Proliferation of external globus pallidus-subthalamic nucleus synapses following degeneration of midbrain dopamine neurons. | |
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MedLine Citation:
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PMID: 23035084 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The symptoms of Parkinson's disease (PD) are related to changes in the frequency and pattern of activity in the reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN). In idiopathic and experimental PD, the GPe and STN exhibit hypoactivity and hyperactivity, respectively, and abnormal synchronous rhythmic burst firing. Following lesion of midbrain dopamine neurons, abnormal STN activity emerges slowly and intensifies gradually until it stabilizes after 2-3 weeks. Alterations in cellular/network properties may therefore underlie the expression of abnormal firing. Because the GPe powerfully regulates the frequency, pattern, and synchronization of STN activity, electrophysiological, molecular, and anatomical measures of GPe-STN transmission were compared in the STN of control and 6-hydroxydopamine-lesioned rats and mice. Following dopamine depletion: (1) the frequency (but not the amplitude) of mIPSCs increased by ∼70%; (2) the amplitude of evoked IPSCs and isoguvacine-evoked current increased by ∼60% and ∼70%, respectively; (3) mRNA encoding α1, β2, and γ2 GABA(A) receptor subunits increased by 15-30%; (4) the density of postsynaptic gephyrin and γ2 subunit coimmunoreactive structures increased by ∼40%, whereas the density of vesicular GABA transporter and bassoon coimmunoreactive axon terminals was unchanged; and (5) the number of ultrastructurally defined synapses per GPe-STN axon terminal doubled with no alteration in terminal/synapse size or target preference. Thus, loss of dopamine leads, through an increase in the number of synaptic connections per GPe-STN axon terminal, to substantial strengthening of the GPe-STN pathway. This adaptation may oppose hyperactivity but could also contribute to abnormal firing patterns in the parkinsonian STN. |
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Authors:
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Kai Y Fan; Jérôme Baufreton; D James Surmeier; C Savio Chan; Mark D Bevan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 32 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-04 Completed Date: 2013-01-17 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 13718-28 Citation Subset: IM |
Affiliation:
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Northwestern University, Physiology, Feinberg School of Medicine, Chicago, Illinois 60611, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carrier Proteins / biosynthesis, genetics Dopamine / physiology* Dopaminergic Neurons / pathology*, physiology Exploratory Behavior / drug effects, physiology Globus Pallidus / pathology*, physiopathology Inhibitory Postsynaptic Potentials / drug effects, physiology Isonicotinic Acids / pharmacology Male Membrane Proteins / biosynthesis, genetics Mice Mice, Inbred C57BL Nerve Degeneration Nerve Tissue Proteins / analysis, biosynthesis, genetics Oxidopamine / toxicity Parkinsonian Disorders / pathology*, physiopathology Patch-Clamp Techniques RNA, Messenger / biosynthesis, genetics Rats Rats, Sprague-Dawley Receptors, GABA-A / biosynthesis, genetics Subthalamic Nucleus / pathology*, physiopathology Synaptic Transmission Vesicular Inhibitory Amino Acid Transport Proteins / biosynthesis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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P50 NS047085/NS/NINDS NIH HHS; P50NS040705/NS/NINDS NIH HHS; R01 NS041280/NS/NINDS NIH HHS; R01 NS069777/NS/NINDS NIH HHS; R01NS069777/NS/NINDS NIH HHS; R37 NS041280/NS/NINDS NIH HHS; R37NS041280/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bsn protein, mouse; 0/Carrier Proteins; 0/Isonicotinic Acids; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/Receptors, GABA-A; 0/Vesicular Inhibitory Amino Acid Transport Proteins; 0/Viaat protein, mouse; 0/gephyrin; 1199-18-4/Oxidopamine; YTF580771Y/isoguvacine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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