Store-operated Ca2+ entry (SOCE) is a ubiquitous mechanism regulating basal and receptor-triggered Ca2+ homeostasis with Stim proteins sensing the ER Ca2+ content and triggering Ca2+ entry by gating Orai channels as well as potentially TRPC1 channels. Given the severe immunological phenotypes that both loss-of-function mutations in either STIM1 or ORAI1 cause in patients and animal models, the role for SOCE in immune cells is well studied. Interestingly, a gain-of-function mutation in STIM1, R304W, causes Stormorken syndrome, with patients suffering from muscular hypotonia, thrombocytopenia, but also miosis and cognitive impairments, with the basis of the cognitive defects not understood on a molecular level. Strong expression of both STIM1 and STIM2 can be found in certain brain regions and in recent years, the Ca2+ hypothesis of neurodegeneration has received increasing attention, postulating that disturbances of ER Calcium homeostasis (decreases or increases) are critically involved in disorders such as Alzheimer disease, Parkinson disease, Huntington or ALS. This hypothesis implicates a direct role for STIM1 and STIM2 as major read-outs of ER Ca2+ concentration, and indeed, neuronal specific loss of STIM2 leads to altered spine morphology and NMDA receptor trafficking and the strong expression of STIM1 in cerebellar Purkinje cells was shown to be involved in mGluR1 mediated changes in synaptic transmission and cerebellar motor behavior, somatic Ca2+ homeostasis and changes in intrinsic firing properties. Exciting new results regarding the function of calcium channels in the brain will be presented in this symposium. The role of Ca2+ stores for microglia function will be discussed by Olga Garaschuk (Germany) using in vivo calcium imaging in different mouse models. Murali Prakriya (USA) will present new results obtained by analyzing both neuronal and glial function in mice with targeted deletions of Orai1 or STIM1. In addition to STIM and ORAI proteins, TRP channels are also important regulators of Ca2+ signaling and short-term plasticity in synapses. Yvonne Schwarz (Germany) will present their influence on fast glutamatergic synapses. In the central nervous system (CNS), neuronal synapse specification can be controlled by a highly selective alternative splicing program and aberrant regulation of splicing is also implicated in multiple neurological disorders. Barbara Niemeyer (Germany) will report on an alternative splice variant of STIM1, which alters synaptic plasticity. Exciting student talks will include analysis of TRPA1 channels in neuroinflammation by Samantha Schmaul (Germany) and changes in subunit compositions of voltage gated Ca2+ channels after traumatic brain injury, presented by Natascha Ihbe (Germany). In sum, this symposium will cover diverse aspects concerning the role of Ca2+ entry pathways into cells of the CNS and their roles in physiological and pathophysiological conditions.

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