Friday, May 20th. 2016 at 11:30 am,
Salle des Conférences (R229), Centre Universitaire des Saints-Pères, 45 rue des Saints-Pères, 75006 Paris
Arthur Konnerth (Institute of Neuroscience, Munich, Germany)
Title: TRPC3-dependent synaptic transmission in central mammalian neurons
The metabotropic glutamate receptor type 1 (mGluR1) is highly expressed in Purkinje cells (PCs) of the mammalian cerebellum. At parallel ber-PC synapses, activation of mGluR1 evokes a complex synaptic response consisting of IP3 receptor-dependent Ca2+ release from endoplasmic reticulum (ER) Ca2+ stores (Takechi et al., Nature, 1998) and a slow excitatory postsynaptic potential (sEPSP) (Batchelor and Garthwaite, Neuropharmacology, 1993). A few years ago, in collaboration with Lutz Birnbaumer, we demonstrated that the sEPSP is mediated by the transient receptor potential (TRPC) channel subunit TRPC3 (Hartmann et al., Neuron 2008). However, the link of mGluR1 to its downstream e ectors remained unknown. We recently tested the possible involvement of the stromal interaction molecule 1 (STIM1), known to interact in non- excitable cells with TRPC channels. Using quantitative single cell RT-PCR and immunostaining, we determined that STIM1 is ten times more abundant than its homolog STIM2 in PCs. We then demonstrated in a newly generated knockout (STIM1pko) mouse line that the PC-speci c deletion of Stim1 caused impairments in cerebellar motor behavior. On the cellular level, we found that in STIM1pko mice, ER Ca2+ stores are largely depleted. Surprisingly, also mGluR1-dependent TRPC3-mediated currents were largely suppressed (Hartmann et al., Neuron, 2014). Together, these results demonstrate that in mammals STIM1 is a key regulator of neuronal Ca2+ signalling,
metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination. ose interested in meeting with the speaker please contact
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