Cellular Integration of Neuromodulatory Processes


Research center

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


Université Pierre et Marie Curie
Université Pierre et Marie Curie


Biological Adaptation and Ageing
UMR 8256


biosensor imaging


Yapo, C., Nair, A.G., Clement, L., Castro, L.R. et al., Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons. J Physiol. 2017, in press, 

Castro, L.R., Brito, M., Guiot, E., Polito, M. et al., Striatal neurones have a specific ability to respond to phasic dopamine release. J Physiol. 2013, 591, 3197-3214.

Castro, L.R., Guiot, E., Polito, M., Paupardin-Tritsch, D. et al., Decoding spatial and temporal features of neuronal cAMP/PKA signaling with FRET biosensors. Biotechnol J. 2014, 9, 192-202.

Polito, M., Guiot, E., Gangarossa, G., Longueville, S. et al., Selective Effects of PDE10A Inhibitors on Striatopallidal Neurons Require Phosphatase Inhibition by DARPP-32. eNeuro. 2015, 2, 1-15.

Nair, A.G., Gutierrez-Arenas, O., Eriksson, O., Vincent, P. et al., Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons. J Neurosci. 2015, 35, 14017-14030.

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.