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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.

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

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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