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INHIBITHUMAN

Financiado
Dis inhibitory circuits in the human cerebral cortex
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 acti... 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. ver más
30/11/2022
UOXF
2M€
Duración del proyecto: 72 meses Fecha Inicio: 2016-11-30
Fecha Fin: 2022-11-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2022-11-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-ADG-2015: ERC Advanced Grant
Cerrada hace 9 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5