HIPPOKAR

Understanding the roles of kainate receptors in the hippocampus

 Coordinatore UNIVERSITY OF BRISTOL 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 2˙500˙000 €
 EC contributo 2˙500˙000 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-ADG
 Funding Scheme ERC-AG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-02-01   -   2019-01-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITY OF BRISTOL

 Organization address address: TYNDALL AVENUE SENATE HOUSE
city: BRISTOL
postcode: BS8 1TH

contact info
Titolo: Ms.
Nome: Sarah
Cognome: Everett-Cox
Email: send email
Telefono: +44 117 9289678

UK (BRISTOL) hostInstitution 2˙500˙000.00
2    UNIVERSITY OF BRISTOL

 Organization address address: TYNDALL AVENUE SENATE HOUSE
city: BRISTOL
postcode: BS8 1TH

contact info
Titolo: Prof.
Nome: Graham Leon
Cognome: Collingridge
Email: send email
Telefono: +44 (0)117 331 1913

UK (BRISTOL) hostInstitution 2˙500˙000.00

Mappa


 Word cloud

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kars    functions    neuronal    hippocampal    gluk    mossy    receptor    function    tools    gc    ltp    glutamate    antagonists    fibre    genetic    kar    ca    record    pharmacological    collaborators   

 Obiettivo del progetto (Objective)

'Kainate receptors (KARs) are often regarded as the last frontier of glutamate receptor research, since much less is known about their physiological roles compared with that of the other glutamate receptor subtypes. This field of research is very important not just because of the unique role that KARs play in neuronal function, including specific forms of synaptic plasticity, but because of the increasing evidence that KARs are involved in a plethora of brain diseases and that KAR antagonists are promising novel therapeutic targets. I propose to lead a highly multidisciplinary approach, in collaboration with colleagues at Bristol and strategic collaborators worldwide, to develop novel pharmacological and genetic tools, which will be rapidly disseminated to the neuroscience community. These tools will be used here to test hypotheses regarding functions of KARs in granule cells (GCs) in the dentate gyrus of the hippocampal formation, with a focus on mossy fibre long-term potentiation (LTP). We propose four interrelated objectives: (i) to develop potent and selective antagonists for the GluK2 subunit of KARs, (ii) to generate GC specific knockouts of the five KAR subunits, by floxing GluK1-5 and crossing with a GC-specific Cre recombinase mouse line, (iii) to use these and existing tools in a combined pharmacological and genetic approach, to understand the functions of KARs at mossy fibre synapses in acute and organotypic hippocampal slices. A new development will be to record simultaneously from synaptically coupled GC-CA3 neuronal pairs and to image Ca2 from participating mossy fibre boutons, (iv) to extend these investigations to the study of mossy fibre function, in particular LTP, in anaesthetised animals and to establish the function of mossy fibre LTP in hippocampus-dependent learning and memory. Although highly ambitious, the proposal is based on a long track record of KAR research by the PI and his collaborators plus a substantial amount of preliminary data.'

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