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In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behavior

Objective

Ligand-gated and voltage-gated channels are key molecules in transforming chemical signals into electrical ones and electrical signals into chemical ones, respectively. At excitatory synaptic connections in the brain, activation of AMPA- and NMDA-type glutamate receptors elicits inward currents at the postsynaptic sites, and activation of voltage-gated calcium channels triggers vesicle release of glutamate in the presynaptic sites. Plastic changes in their number, location and property can lead to potentiation or depression of synaptic efficacy, alteration in time course, and coupling to effectors at both postsynaptic and presynaptic sites. These channels are all composed of distinct subunits and their compositions affect channel properties, trafficking to the synaptic sites, and interaction with associated molecules, creating a large diversity of synaptic functions. Although channels with different subunit compositions have been investigated using biochemical and electrophysiological detection methods, very little is known about single channel subunit composition in situ because of the lack of high resolution methods for analysis of protein complex in intact tissues. In this project, I will develop novel technologies to visualize subunit composition at the single channel level in individual synapses by electron microscopy, combining new EM tags, freeze-fracture replica labelling, and electron tomography. Synaptic plasticity will be induced by optogenetic stimulation of identified neurons or behavioural paradigms to examine the dynamic changes of subunit composition. Finally, physiological implications of such regulation of subunit composition will be investigated by genetic manipulation of mice combined with electrophysiological and behavioural analyses. This work will demonstrate unprecedented views of the subunit composition in situ and provide new insights into how regulation of subunit composition contributes to synaptic plasticity and animal behaviour.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2015-AdG

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Host institution

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 481 437,00
Address
Am Campus 1
3400 KLOSTERNEUBURG
Austria

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Region
Ostösterreich Niederösterreich Wiener Umland/Nordteil
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 481 437,00

Beneficiaries (1)

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