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Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons
KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Manipal Univ, India.ORCID-id: 0000-0002-1952-9583
KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.ORCID-id: 0000-0003-0740-4318
Vise andre og tillknytning
2015 (engelsk)Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, nr 41, s. 14017-14030Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Transient changes in striatal dopamine (DA) concentration are considered to encode a reward prediction error (RPE) in reinforcement learning tasks. Often, a phasic DA change occurs concomitantly with a dip in striatal acetylcholine (ACh), whereas other neuromodulators, such as adenosine (Adn), change slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs for these neuromodulators in striatal medium spiny neurons (MSNs), which play important roles in plasticity. However, little is known about the interaction between these neuromodulators via GPCRs. The interaction between these transient neuromodulator changes and the effect on cAMP/PKA signaling via Golf- and Gi/o-coupled GPCR are studied here using quantitative kinetic modeling. The simulations suggest that, under basal conditions, cAMP/PKA signaling could be significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an ACh dip is required to gate a subset of D1R/Golf-dependent PKA activation. Furthermore, the interaction between ACh dip and DA peak, via D1R and M4R, is synergistic. In a similar fashion, PKA signaling in D2+ MSNs is under basal inhibition via D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting A2aR/Golf, but D2+ MSNs could also respond to the DA peak via other intracellular pathways. This study highlights the similarity between the two types of MSNs in terms of high basal AC inhibition by Gi/o and the importance of interactions between Gi/o and Golf signaling, but at the same time predicts differences between them with regard to the sign of RPE responsible for PKA activation.

sted, utgiver, år, opplag, sider
2015. Vol. 35, nr 41, s. 14017-14030
Emneord [en]
acetylcholine; D1R/M4R; D2R/A2AR; dopamine; reward learning; striatal plasticity
HSV kategori
Forskningsprogram
SRA - Molekylär biovetenskap
Identifikatorer
URN: urn:nbn:se:kth:diva-175697DOI: 10.1523/JNEUROSCI.0730-15.2015ISI: 000366051800022PubMedID: 26468202Scopus ID: 2-s2.0-84944542200OAI: oai:DiVA.org:kth-175697DiVA, id: diva2:861947
Merknad

A.G.N. and O.G.-A. contributed equally to this work.

QC 20150108

Tilgjengelig fra: 2015-10-19 Laget: 2015-10-19 Sist oppdatert: 2022-06-23bibliografisk kontrollert

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Nair, Anu G.Eriksson, OliviaHellgren Kotaleski, Jeanette

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