RGD Reference Report - RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion. - Rat Genome Database

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RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion.

Authors: Ding, Jun  Guzman, Jaime N  Tkatch, Tatiana  Chen, Songhai  Goldberg, Joshua A  Ebert, Philip J  Levitt, Pat  Wilson, Charles J  Hamm, Heidi E  Surmeier, D James 
Citation: Ding J, etal., Nat Neurosci. 2006 Jun;9(6):832-42. doi: 10.1038/nn1700. Epub 2006 May 14.
RGD ID: 13524538
Pubmed: PMID:16699510   (View Abstract at PubMed)
DOI: DOI:10.1038/nn1700   (Journal Full-text)

Parkinson disease is a neurodegenerative disorder whose symptoms are caused by the loss of dopaminergic neurons innervating the striatum. As striatal dopamine levels fall, striatal acetylcholine release rises, exacerbating motor symptoms. This adaptation is commonly attributed to the loss of interneuronal regulation by inhibitory D(2) dopamine receptors. Our results point to a completely different, new mechanism. After striatal dopamine depletion, D(2) dopamine receptor modulation of calcium (Ca(2+)) channels controlling vesicular acetylcholine release in interneurons was unchanged, but M(4) muscarinic autoreceptor coupling to these same channels was markedly attenuated. This adaptation was attributable to the upregulation of RGS4-an autoreceptor-associated, GTPase-accelerating protein. This specific signaling adaptation extended to a broader loss of autoreceptor control of interneuron spiking. These observations suggest that RGS4-dependent attenuation of interneuronal autoreceptor signaling is a major factor in the elevation of striatal acetylcholine release in Parkinson disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of calcium ion transport  IDA 13524538 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rgs4  (regulator of G-protein signaling 4)


Additional Information