Obiettivo 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. Campo scientifico natural sciencesbiological scienceszoologymammalogysocial sciencespsychologycognitive psychology Parole chiave interneuron GABA cerebral cortex electrophysiology synaptic transmission synaptic receptors Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-ADG-2015 - ERC Advanced Grant Invito a presentare proposte ERC-2015-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Contribution nette de l'UE € 1 796 038,00 Indirizzo WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Regno Unito Mostra sulla mappa Regione South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 796 038,00 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Regno Unito Contribution nette de l'UE € 1 796 038,00 Indirizzo WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Mostra sulla mappa Regione South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 796 038,00 AARHUS UNIVERSITET Danimarca Contribution nette de l'UE € 703 875,00 Indirizzo NORDRE RINGGADE 1 8000 Aarhus C Mostra sulla mappa Regione Danmark Midtjylland Østjylland Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 703 875,00
