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INHIBITHUMAN SIGNED

Dis-inhibitory circuits in the human cerebral cortex

Total Cost €

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EC-Contrib. €

0

Partnership

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 INHIBITHUMAN project word cloud

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

resolution    inhibit    first    modulating    governed    glutamatergic    cells    cns    inhibition    plastic    human    enhancers    interventions    underlies    mglurs    events    overarching    strategies    neuron    mediated    small    cortex    neuropharmacology    cerebral    receptors    influences    elucidate    modulation    temporal    plasticity    ordination    physiological    mammals    act    endocannabinoids    molecule    pharmacological    ach    hypotheses    interneurons    mechanisms    synaptic    dependent    neurons    circuits    gabaergic    action    output    windows    sites    regulators    imaging    alteration    localisation    cortical    drugs    therapeutic    occurs    generate    redistribution    subcellular    characterise    pyramidal    molecular    neuronal    firing    connections    combined    neuropeptides    monoamines    gated    dis    cell    types    inhibitory    dynamics    cognitive    receptor    controls    unprecedented    operations    altering    cellular    specialised    co    substrates    intracortical    integration    electrophysiology    compartment   

Project "INHIBITHUMAN" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

Organization address
address: WELLINGTON SQUARE UNIVERSITY OFFICES
city: OXFORD
postcode: OX1 2JD
website: www.ox.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]
 Total cost 2˙499˙913 €
 EC max contribution 2˙499˙913 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-12-01   to  2021-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) coordinator 1˙796˙038.00
2    AARHUS UNIVERSITET DK (AARHUS C) participant 703˙875.00

Map

 Project objective

Temporal co-ordination of the activity of cortical neurons underlies cognitive processes. Intracortical inhibitory circuits set temporal windows for modulation of glutamatergic pyramidal cell firing. In non-human mammals, the activity of the GABAergic neurons is governed by other specialised GABAergic neurons, which can dis-inhibit pyramidal cells. The overarching aim of this project is to define cellular and pharmacological mechanisms of dis-inhibitory circuits in the human cerebral cortex. These circuits could act as regulators of cognitive process. First, we will investigate the neuron types and their synaptic influences to characterise how dis-inhibition controls synaptic integration and the output of neurons. Second, we will elucidate synaptic plasticity in dis-inhibitory circuits, as plastic events likely represent physiological substrates of cognitive operations. Third, we will identify the subcellular sites and the mechanisms of action of key receptors for ACh, monoamines, endocannabinoids, neuropeptides and mGluRs modulating dis-inhibitory circuits, which are targets of small molecule CNS drugs, such as cognitive enhancers. We will test three hypotheses: 1) the human cortical pyramidal cell output is gated by compartment-specific dis-inhibition mediated by specific interneurons; 2) activity-dependent plasticity occurs in dis-inhibitory circuits and has consequences for the output of cortical pyramidal neurons; 3) small molecule drugs act via dis-inhibitory mechanisms at cell-type specific sites altering the inhibitory dynamics of pyramidal cells leading to subcellular redistribution of inhibition and alteration in their output. Combined electrophysiology/imaging with neuropharmacology and high resolution molecular receptor localisation will generate an unprecedented knowledge of the human cortical circuits. Understanding human cortical neuronal connections and their responses to pharmacological interventions may also lead to novel therapeutic strategies.

 Publications

year authors and title journal last update
List of publications.
2019 Marco Bocchio, Istvan P. Lukacs, Richard Stacey, Puneet Plaha, Vasileios Apostolopoulos, Laurent Livermore, Arjune Sen, Olaf Ansorge, Martin J. Gillies, Peter Somogyi, Marco Capogna
Group II Metabotropic Glutamate Receptors Mediate Presynaptic Inhibition of Excitatory Transmission in Pyramidal Neurons of the Human Cerebral Cortex
published pages: , ISSN: 1662-5102, DOI: 10.3389/fncel.2018.00508
Frontiers in Cellular Neuroscience 12 2019-08-29

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