Document Detail


Proliferation of external globus pallidus-subthalamic nucleus synapses following degeneration of midbrain dopamine neurons.
MedLine Citation:
PMID:  23035084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kai Y Fan; Jérôme Baufreton; D James Surmeier; C Savio Chan; Mark D Bevan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13718-28     Citation Subset:  IM    
Affiliation:
Northwestern University, Physiology, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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

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