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INHIBITHUMAN SIGNED

Dis-inhibitory circuits in the human cerebral cortex

Total Cost €

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EC-Contrib. €

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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.

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

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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