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Contenu archivé le 2022-12-23

Calcium stores in single synaptic boutons: role in synaptic transmission

Objectif

The endoplasmic reticulum (ER) calcium stores are an indispensable source for Ca2+ signals involved in physiological responses of various types of non-excitable and excitable cells. The ER membrane in essence forms an intracellular excitable media, which can produce both synchronous release and calcium waves within single cells and multicellular networks. The objective of this project is to test the hypothesis that the local Ca2+ release from the ER store present in the synaptic terminal is involved in the regulation of neurotransmitter release and synaptic plasticity. This hypothesis, though being proposed previously, has not been proven yet by direct experimental observations.
The experiments will be performed on a low-density primary culture of rat hippocampal neurones. Presynaptic [Ca2+]i and postsynaptic membrane currents will be measured simultaneously by combination of whole-cell patch-clamp recordings and fluorescent video-imaging. The single synaptic terminals will be visualised by FM1-43 staining; resulting image will be used as a region of interest for [Ca2+]i recordings.

The experiments will be designed to
(i) visualise ER Ca2+ store in the single synaptic terminal;
(ii) investigate [Ca2+]i dynamics in a single synaptic terminal in response to stimulation of Ca2+ release from the ER;
(iii) correlate presynaptic [Ca2+]i dynamics with synaptic strength, measured by postsynaptic currents monitoring;
(iv) identify the involvement of ER Ca2+ store in regulation of synaptic transmission at the level of single terminal and;
(v) develop a mathematical model describing the relations between Ca2+ entry/Ca2+ release during presynaptic excitation and the relative importance of these pathways in regulating synaptic plasticity.

Appel à propositions

Data not available

Régime de financement

Data not available

Coordinateur

University of Manchester
Contribution de l’UE
Aucune donnée
Adresse
Oxford Road
M13 9PT Manchester
Royaume-Uni

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Coût total
Aucune donnée

Participants (3)