CRM: Centro De Giorgi
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Nanoscale mathematical modeling of synaptic transmission, calcium dynamics, transduction and cell sensing

course: The role of calcium compartmentalization in neuronal plasticity and new spine formation

speaker: Eduard Korkotian (Weizmann)

abstract: It is well established that neurons are plastic and can change the strength of their connections with other neurons depending on their recent history. While many molecular entities involved in plastic processes were already described, the role of a store-operated calcium channel ORAI1 in neuronal plasticity is not known. The store depletion resulted in an increase in stromal interacting molecule 2 (an endoplasmic calcium sensor) association with Orai1 in dendritic spines. The response to the rise in calcium was larger in spines endowed with a cluster of Orai1 molecules than in spines devoid of Orai1. Transfection of neurons with a dominant negative Orai1 resulted in retarded maturation of dendritic spines, a reduction in synaptic connectivity with afferent neurons and a reduction in the ability to undergo morphological changes following induction of chemical long-term potentiation. Similarly, small interfering RNA (siRNA)-treated neurons had fewer mature dendritic spines, and lower rates of mEPSCs compared to scrambled control siRNA-treated neurons. Using dominant negative form of ORAI1, we were able to show that ORAI1 is also needed for formation of new spines following chemical induction of long term potentiation (cLTP), and that this is due to the release of calcium from ryanodine receptor-associated endoplasmic reticulum stores. We propose that when ORAI1 is deficient, there is less calcium in the stores, less releasable calcium and consequently less cLTP and spine formation. Thus, influx of calcium through Orai1 channels facilitates the maturation of dendritic spines and the formation of functional synapses.

Wed 10 Oct, 9:30 - 10:30, Aula Dini
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