Synaptic plasticity-induced ERK dynamics in striatal projection neurons
Dates:9 July 2018 - 28 September 2018
Date limite de candidature:9 July 2018
~ July-Sept 2018
The striatum is a major entry structure of the basal ganglia. It receives a convergent excitatory glutamate input (from cortex and thalamus), controlled by dopamine (DA) released. DA receptors are segregated into distinct neuronal populations in the striatum, D1R expressing SPN and D2R SPN. In D1-SPN, the extracellular signal-regulated kinase (ERK) kinase pathway can detects combination of glutamate and dopamine release and is essential for long-lasting modifications. In addition, striatal plasticity is significantly altered in pathological conditions in which either a loss of DA innervation (Parkinson’s disease) or aberrant DA release (drug addiction and L-DOPA induced dyskinesia) occurs.
The spatiotemporal activation of ERK pathways in D1 SPN in responses to synaptic plasticity relevant activation is unknown. To gain deeper insights ERK pathway dynamics in SPN, we will combine multiphoton microscopy with FRET biosensors, pharmacological stimulation and/or LTP induction in adult mice striatal slices. The project will start by using pharmacological stimulation like D1R and/or glutamatergic receptor agonist to activate ERK pathway. The expected results will show that co-stimulation produce a synergistic activation of ERK pathway. The next step will be to test different long-term plasticity protocols and to record using multiphoton imaging ERK dynamics in SPN. We will also use pharmacological inhibition of the ERK pathway (by U0126) to understand if specific ERK activation are involved in LTP induction or maintenance.
The mechanisms involved in the induction of striatal LTP appears to be extremely complex. We think that imaging intracellular signalling pathways will help to understand the discrepancy between various LTP protocols. And extract the central role of ERK dynamics in the long term regulation of SPNs.
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