Cellular Integration of Neuromodulatory Processes

Leader

Research center

9 Quai Saint-Bernard Université Pierre et Marie Curie, Campus Jussieu, Bâtiments A-B-C
75005 Paris
Michel Labouesse

Institution

CNRS
Université Pierre et Marie Curie
ED158
Université Pierre et Marie Curie

Laboratory

Biological Adaptation and Ageing
UMR 8256

Keywords

biosensor imaging
striatum
dopamine
Parkinson
schizophrenia
Available to host a PhD student

Publications

Polito, Klarenbeek, Jalink, Paupardin-Tritsch, Vincent & Castro, “The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons.”, Front Cell Neurosci, 7, 211, 2013. DOI=10.3389/fncel.2013.00211 PMID=24302895 

Castro, Guiot, Polito, Paupardin-Tritsch et Vincent, 2014, “Decoding spatial and temporal features of neuronal cAMP/PKA signaling with FRET biosensors.” Biotechnol J., in press, DOI:10.1002/biot.201300202.

Erard M, Fredj A, Pasquier H, Beltolngar DB, Bousmah Y, Derrien V, #Vincent P, Merola F. (2013) Minimum set of mutations needed to optimize cyan fluorescent proteins for live cell imaging. Mol Biosyst;9:258/67.

Castro, Brito, Guiot, Polito, Korn, Hervé, Girault, Paupardin-Tritsch & Vincent, “Striatal neurones have a specific ability to respond to phasic dopamine release.”, J. Physiol., 591(13), p3197–3214, 2013. DOI=10.1113/jphysiol.2013.252197 PMID=23551948

Vincent, Castro, Gervasi, Guiot, Brito & Paupardin-Tritsch, “PDE4 control on cAMP/PKA compartmentation revealed by biosensor imaging in neurons.”, Horm Metab Res, 44, 786-789, 2012. DOI=10.1055/s-0032-1311631 PMID=22581649

Hu, Demmou, Cauli, Gallopin, Geoffroy, Harris-Warrick, Paupardin-Tritsch, Lambolez, Vincent & Hepp, “VIP, CRF, and PACAP Act at Distinct Receptors to Elicit Different cAMP/PKA Dynamics in the Neocortex.”, Cereb Cortex, 21, 708-718, 2011. DOI=10.1093/cercor/bhq143 PMID=20699230

Castro, Gervasi, Guiot, Cavellini, Nikolaev, Paupardin-Tritsch & Vincent, “Type 4 phosphodiesterase plays different integrating roles in different cellular domains in pyramidal cortical neurons.”, J. Neurosci., 30, 6143-6151, 2010. DOI=10.1523/JNEUROSCI.5851-09.2010 PMID=20427672

Hepp, Tricoire, Hu, Gervasi, Paupardin-Tritsch, Lambolez & Vincent, “Phosphodiesterase type 2 and the homeostasis of cyclic GMP in living thalamic neurons.”, J. Neurochem., 102, 1875-1886, 2007. DOI=10.1111/j.1471-4159.2007.04657.x PMID=17561940

Fields of research

Neuropharmacology / cell signaling

Research Theme

Mesencephalic dopaminergic neurons project towards various brain regions, including the striatum and the prefrontal cortex. Dopamine is involved in the modulation of a number of functions in the central nervous system (reward, attention, motor programs), and dysfunctions in dopaminergic signaling are associated with severe neuropsychiatric diseases (Parkinson's disease, addiction, schizophrenia…) Using a novel biosensor imaging approach, our team has revealed the importance of neuronal architecture and enzymatic equipment in the integration of the dopamine signal via the cAMP/PKA signaling cascade. Compared to the cortex, we observed that striatal neurons strongly and rapidly respond to dopamine, conferring on these neurons an exceptional ability to respond to very brief dopaminergic stimulations (100 ms) such as those involved in learning and reward.

A number of neuropsychiatric diseases are related to dysfunctions in neuromodulatory signaling. We are currently examining the functional role played by phosphodiesterases, which regulate the cAMP signal, in the striatum. More precisely, type 10 phosphodiesterase is a novel target for schizophrenia treatment and we are deciphering the mechanism of action of PDE10 inhibitors in the striatum using our biosensor imaging approach.

Team members

Liliana Castro
Elvire Guiot
Danièle Paupardin-Tritsch

Lab rotation

Cellular Integration of Neuromodulatory Processes

Team leader: 

VINCENT Pierre

Dates: 

January 2, 2018 - June 29, 2018

Application deadline: 

June 29, 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

Parkinson's disease is characterized by the progressive loss ofdopaminergic terminals. Its treatment with L-DOPAprogressively leads to an invalidating dyskinetic status. Whiledopamine neuromodulation has been largely studied, thestriatum is also the target of a strong serotonin innervation,which functional implication remains largely unknown.Serotonin afferents remain essentially functional in Parkinson'sdisease. These terminals also release dopamine, producedfrom L-DOPA. In addition, the dyskinetic status induced bychronic L-DOPA treatment is associated with an increasedexpression of 5-HT1B receptors, and inhibition of thesereceptors reduce these dyskinesia.We use a dynamic approach of signaling processes based onbiosensor imaging, and already analyzed some aspects of theD1 and D2 responses to dopamine in striatal spiny neurons ofthe direct and indirect pathways, respectively. Preliminary datashow that positive and negative cAMP responses to serotonineare also segregated on the two types of striatal neurons. Wenow want to characterize the integration of serotonin effect,together with the other main neuromodulatory signals in thestriatum, and study the adaptation of these signaling events inthe chronic condition of Parkinson's disease.

Contact

Institut de Biologie Paris Seine - 9 quai St Bernard 75005 Paris - +33 1 44 27 25 88 - pierre.vincent@upmc.fr

Supervisor: 

VINCENT Pierre