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HomeoBalanceExcInh SIGNED

Homeostatic balancing of excitation and inhibition in vivo

Total Cost €

0

EC-Contrib. €

0

Partnership

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 HomeoBalanceExcInh project word cloud

Explore the words cloud of the HomeoBalanceExcInh project. It provides you a very rough idea of what is the project "HomeoBalanceExcInh" about.

mediates    schizophrenia    despite    apl    enhances    maintaining    regulated    establishing    responsiveness    linked    gap    compensate    projection    bounds    elucidating    coding    reveal    pns    feedback    intact    reducing    adapt    receive    memory    uncover    cellular    levels    tools    first    deviations    single    opportunity    neurons    balanced    genetically    tractable    forces    adjusting    plasticity    progress    inhibition    specificity    neural    molecular    neuron    breaking    time    sparse    perturbed    circuit    balancing    pn    prolonged    model    vivo    powerful    depends    diseases    homeostatic    disruption    function    olfactory    drosophila    overlap    little    autism    preparations    normal    candidate    mechanisms    genes    kenyon    kcs    cells    kc    epilepsy    perturbations    representations    fundamental    associative    maintains    preliminary    indicates    brain    underlying    odour    sophisticated    genetic    excitation    balance    ground   

Project "HomeoBalanceExcInh" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF SHEFFIELD 

Organization address
address: FIRTH COURT WESTERN BANK
city: SHEFFIELD
postcode: S10 2TN
website: www.shef.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website http://www.aclinlab.org
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-10-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF SHEFFIELD UK (SHEFFIELD) coordinator 1˙500˙000.00

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 Project objective

Balanced excitation and inhibition is a fundamental principle of neural circuit function, and perturbed excitation/inhibition (E/I) balance has been linked to diseases such as epilepsy, autism and schizophrenia. Maintaining E/I balance within normal bounds depends in part on homeostatic plasticity, in which neurons compensate for deviations in activity levels by adjusting their responsiveness to excitation and inhibition. Yet despite recent progress in elucidating molecular mechanisms underlying homeostatic plasticity in reduced preparations, little is known about such mechanisms in the intact brain.

I propose to address this gap using a simple and genetically tractable neural circuit that I recently characterized. In Drosophila, Kenyon cells (KCs), the neurons underlying olfactory associative memory, receive excitation from projection neurons (PNs) as well as feedback inhibition from a single identified neuron (‘APL’). The balance between these two forces maintains sparse odour coding in KCs, which enhances the odour-specificity of associative memory by reducing overlap between odour representations.

Preliminary evidence indicates that KCs adapt to prolonged disruption of E/I balance, providing a ground-breaking opportunity to use the powerful genetic tools of Drosophila to uncover the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in vivo in a defined circuit that mediates a sophisticated behaviour.

Specific aims: 1. Characterize homeostatic plasticity in the PN-KC-APL circuit. 2. Identify genes up- and down-regulated in response to perturbations of E/I balance. 3. Determine role of candidate genes and cellular mechanisms in homeostatic plasticity.

Establishing the PN-KC-APL circuit as a novel model system for homeostatic plasticity will reveal for the first time the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in the intact brain.

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