Cellular Integration of Neuromodulatory Processes
Dates:January 2, 2018 - June 29, 2018
Application deadline:June 29, 2018
~ Jan-March 2018
~ April-June 2018
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.
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