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Publication

Regulation of synaptic MAPK/ERK phosphorylation in the rat striatum and medial prefrontal cortex by dopamine and muscarinic acetylcholine receptors.

Bing Xue | Li-Min Mao | Dao-Zhong Jin | John Q Wang

Journal of neuroscience research | 2015

Dopamine and acetylcholine are two principal transmitters in the striatum and are usually balanced to modulate local neural activity and to maintain striatal homeostasis. This study investigates the role of dopamine and muscarinic acetylcholine receptors in the regulation of a central signaling protein, i.e., the mitogen-activated protein kinase (MAPK). We focus on the synaptic pool of MAPKs because of the fact that these kinases reside in peripheral synaptic structures in addition to their somatic locations. We show that a systemic injection of dopamine D1 receptor (D1R) agonist SKF81297 enhances phosphorylation of extracellular signal-regulated kinases (ERKs), a prototypic subclass of MAPKs, in the adult rat striatum. Similar results were observed in another dopamine-responsive region, the medial prefrontal cortex (mPFC). The dopamine D2 receptor agonist quinpirole had no such effects. Pretreatment with a positive allosteric modulator (PAM) of muscarinic acetylcholine M4 receptors (M4Rs), VU0152100, attenuated the D1R agonist-stimulated ERK phosphorylation in the two regions, whereas the PAM itself did not alter basal ERK phosphorylation. All drug treatments had no effect on phosphorylation of c-Jun N-terminal kinases (JNKs), another MAPK subclass, in the striatum and mPFC. These results demonstrate that dopamine and acetylcholine are integrated to control synaptic ERK but not JNK activation in striatal and mPFC neurons in vivo. Activation of M4Rs exerts an inhibitory effect on the D1R-mediated upregulation of synaptic ERK phosphorylation.

Pubmed ID: 26153447 RIS Download

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Antibodies used in this publication

Associated grants

Agency: NIDA NIH HHS, United States
Id: R01 DA010355
Agency: NIMH NIH HHS, United States
Id: R01 MH061469

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This is a list of tools and resources that we have found mentioned in this publication.

SAPK/JNK Antibody (antibody)

RRID:AB_2250373

This polyclonal targets SAPK/JNK

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p44/42 MAP kinase (phosphorylated Erk1/2) (antibody)

RRID:AB_331646

This polyclonal targets Erk1/2

View all literature mentions

Anti-Actin antibody produced in rabbit (antibody)

RRID:AB_476693

This polyclonal targets Actin

View all literature mentions

Phospho-SAPK/JNK (Thr183/Tyr185) Antibody (antibody)

RRID:AB_331659

This polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)

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p44/42 MAPK (Erk1/2) Antibody (antibody)

RRID:AB_330744

This polyclonal targets p44/42 MAPK (Erk1/2)

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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