Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA.

ELife
Se Joon ChoiUn Jung Kang

Abstract

Changes in striatal cholinergic interneuron (ChI) activity are thought to contribute to Parkinson's disease pathophysiology and dyskinesia from chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, but the physiological basis of these changes is unknown. We find that dopamine lesion decreases the spontaneous firing rate of ChIs, whereas chronic treatment with L-DOPA of lesioned mice increases baseline ChI firing rates to levels beyond normal activity. The effect of dopamine loss on ChIs was due to decreased currents of both hyperpolarization-activated cyclic nucleotide-gated (HCN) and small conductance calcium-activated potassium (SK) channels. L-DOPA reinstatement of dopamine normalized HCN activity, but SK current remained depressed. Pharmacological blockade of HCN and SK activities mimicked changes in firing, confirming that these channels are responsible for the molecular adaptation of ChIs to dopamine loss and chronic L-DOPA treatment. These findings suggest that targeting ChIs with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in PD patients.

References

Apr 1, 1976·Journal of Neurology, Neurosurgery, and Psychiatry·M J WelchD J Jenden
Aug 1, 1967·Archives of Neurology·R C Duvoisin
Nov 1, 1967·Neurology·R C Duvoisin, W D Dettbarn
Nov 3, 2001·Science·P Greengard
Sep 5, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·S L PimlottD Wyper
Nov 19, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicolas MauriceD James Surmeier
Sep 16, 2005·Journal of Neurophysiology·Charles J Wilson, Joshua A Goldberg
Nov 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joshua A Goldberg, Charles J Wilson
Mar 23, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ping DengZao C Xu
Sep 15, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shiaoching GongCharles R Gerfen
Apr 4, 2009·Neurobiology of Disease·Pascal SalinJosé L Lanciego
May 22, 2009·Journal of Neurophysiology·Susan E Atkinson, Stephen R Williams
Jul 3, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joshua A GoldbergCharles J Wilson
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Elisenda SanzPaul S Amieux
Nov 16, 2010·Nature Neuroscience·C Savio ChanD James Surmeier
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yunmin DingUn Jung Kang
Apr 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gonzalo SanchezMario Gustavo Murer
Jan 10, 2012·Handbook of Experimental Pharmacology·Joshua A GoldbergD James Surmeier
Mar 8, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maxime CazorlaChristoph Kellendonk
May 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·John R BankstonWilliam N Zagotta
Sep 4, 2012·Journal of Neuroscience Methods·D KoC A Paladini
Nov 28, 2013·The Journal of General Physiology·Lei HuSteven Siegelbaum
Feb 21, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lisa WonUn Jung Kang
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Andrea SaponaroAnna Moroni
Sep 30, 2014·Nature Methods·Tiago A FerreiraDonald J van Meyel
Dec 11, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Stanley Fahn
Jan 23, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mark T HarnettStephen R Williams
Feb 11, 2015·Neurobiology of Disease·Sean Austin O LimUn Jung Kang
Jun 23, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Marc Deffains, Hagai Bergman

❮ Previous
Next ❯

Citations

Mar 30, 2021·Frontiers in Neuroscience·Kai YangTaolei Sun
May 29, 2021·Neuroscience·Rodrigo Manuel Paz, Mario Gustavo Murer
Feb 7, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Rodrigo Manuel PazMario Gustavo Murer

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy
PCR
immunoprecipitation

Software Mentioned

MatLab
GraphPad Prism
ImageJ )
GraphPad
Mini Analysis
Igor Pro
WINWCP
Fiji
Power
Clampfit

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.