{"entity": "researcher", "timestamp": "2026-09-01T08:31:46.310Z", "family": "Vincent", "given": "Pierre", "initials": "P", "orcid": "0000-0002-8479-1908", "affiliations": ["CNRS, UMR8256 \"Biological Adaptation and Ageing\", Institut de Biologie Paris-Seine (IBPS), F-75005, Paris, France.", "Universit\u00e9 Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universit\u00e9s, F-75005, Paris, France."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f2aa0ba6eb1411a9880e18896eb043e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f2aa0ba6eb1411a9880e18896eb043e"}}, "publications": [{"entity": "publication", "iuid": "8df0819dd5dc41b1abc8803279bb03d7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8df0819dd5dc41b1abc8803279bb03d7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8df0819dd5dc41b1abc8803279bb03d7"}}, "title": "Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.", "authors": [{"family": "Yapo", "given": "Cedric", "initials": "C"}, {"family": "Nair", "given": "Anu G", "initials": "AG"}, {"family": "Clement", "given": "Lorna", "initials": "L"}, {"family": "Castro", "given": "Liliana R", "initials": "LR"}, {"family": "Hellgren Kotaleski", "given": "Jeanette", "initials": "J"}, {"family": "Vincent", "given": "Pierre", "initials": "P", "orcid": "0000-0002-8479-1908", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f2aa0ba6eb1411a9880e18896eb043e.json"}}], "type": "journal article", "published": "2017-12-15", "journal": {"title": "J. Physiol. (Lond.)", "issn": "1469-7793", "volume": "595", "issue": "24", "pages": "7451-7475", "issn-l": "0022-3751"}, "abstract": "Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level.\n\nThe phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D2 than on D1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine. Overall, our results show that D2 MSNs may sense much more complex patterns of dopamine than previously thought.", "doi": "10.1113/JP274475", "pmid": "28782235", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5730852"}], "notes": [], "created": "2018-12-05T11:55:57.166Z", "modified": "2026-08-21T09:30:00.391Z"}, {"entity": "publication", "iuid": "7396b1cbbf1841fdb0afb7a229eb9416", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7396b1cbbf1841fdb0afb7a229eb9416.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7396b1cbbf1841fdb0afb7a229eb9416"}}, "title": "Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons.", "authors": [{"family": "Nair", "given": "Anu G", "initials": "AG"}, {"family": "Gutierrez-Arenas", "given": "Omar", "initials": "O"}, {"family": "Eriksson", "given": "Olivia", "initials": "O"}, {"family": "Vincent", "given": "Pierre", "initials": "P", "orcid": "0000-0002-8479-1908", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f2aa0ba6eb1411a9880e18896eb043e.json"}}, {"family": "Hellgren Kotaleski", "given": "Jeanette", "initials": "J"}], "type": "journal article", "published": "2015-10-14", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "volume": "35", "issue": "41", "pages": "14017-14030", "issn-l": "0270-6474"}, "abstract": "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.\n\nDopamine transients are considered to carry reward-related signal in reinforcement learning. An increase in dopamine concentration is associated with an unexpected reward or salient stimuli, whereas a decrease is produced by omission of an expected reward. Often dopamine transients are accompanied by other neuromodulatory signals, such as acetylcholine and adenosine. We highlight the importance of interaction between acetylcholine, dopamine, and adenosine signals via adenylyl-cyclase coupled GPCRs in shaping the dopamine-dependent cAMP/PKA signaling in striatal neurons. Specifically, a dopamine peak and an acetylcholine dip must interact, via D1 and M4 receptor, and a dopamine dip must interact with adenosine tone, via D2 and A2a receptor, in direct and indirect pathway neurons, respectively, to have any significant downstream PKA activation.", "doi": "10.1523/JNEUROSCI.0730-15.2015", "pmid": "26468202", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC4604235"}, {"db": "pii", "key": "35/41/14017"}], "notes": [], "created": "2018-12-05T10:13:07.936Z", "modified": "2026-08-21T12:53:23.439Z"}]}