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PIANISM SIGNED

Prefrontal Cortex Circuit Dynamics underlying Working Memory and its Serotonin Modulation

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EC-Contrib. €

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Partnership

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 PIANISM project word cloud

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

persistent    mechanism    dysfunctional    ionic    raphe    ve    impaired    transmission    memory    networks    neurons    electrophysiology    gabaergic    supports    protein    imaging    serotonin    perform    synaptic    cells    chronic    pv    mechanistic    sst    schizophrenia    mediated    currents    circuits    disorders    drive    serotonergic    modulation    deficiencies    pharmacologically    cellular    sustained    intracellular    deficient    patch    regulation    maintenance    deficits    coupled    underlying    dependent    calcium    therapeutic    vip    examine    causing    clamp    deficiency    cortex    axons    na    initial    mental    experiments    plan    decision    poorly    genetically    intrinsic    iuml    inward    fulfill    types    modulated    receptor    experimental    model    signalling    slices    enabled    indicators    ketamine    action    encoded    optical    mechanisms    trpc    acute    understand    nuclei    subtypes    wm    firing    data    sensitive    optogenetically    learning    pfc    cognitive    express    5ht    density    pyramidal    mice    cell    outlasts    projected    dysfunctions    sodium    prefrontal    excitatory    link    neuronal    gain    alterations    voltage   

Project "PIANISM" data sheet

The following table provides information about the project.

Coordinator		 IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.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 212˙933 €
 EC max contribution 212˙933 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2019
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2020
 Duration (year-month-day) from 2020-05-01   to  2022-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 212˙933.00

Map

 Project objective

The prefrontal cortex (PFC) is essential for higher cognitive tasks such as learning, decision making and, in particular, working memory (WM). To fulfill these tasks, PFC neurons express several serotonin (5HT) receptor subtypes that are modulated by a high density of serotonergic axons projected from the raphe nuclei. Alterations of the neuronal mechanisms within PFC lead to an impaired top-down regulation, causing cognitive dysfunctions in mental disorders such as schizophrenia. A key cellular mechanism related to WM formation and maintenance in the PFC is sustained action potential firing of neurons that outlasts the initial excitatory drive. Persistent firing is likely enabled by synaptic networks and intracellular ionic mechanisms, including voltage sensitive sodium and calcium inward currents or G-Protein-coupled receptor mediated TRPC/ CAN currents. Moreover, experimental data supports a link between dysfunctional serotonergic modulation in the PFC and WM deficits, but yet, the underlying mechanisms are poorly understood. Here, I plan to gain a mechanistic understanding of the serotonergic modulation of WM at the cellular level including the link between 5HT receptor activity and prefrontal cellular circuits dependent WM formation and the role of 5HT in WM-related persistent firing. I will perform patch-clamp electrophysiology and optical voltage imaging (genetically encoded voltage indicators) of prefrontal pyramidal and GABAergic cells (PV-, SST-, VIP-subtypes) in acute slices from naïve and WM deficient mice (chronic ketamine model of schizophrenia), and examine how the activity of these cell types are modulated by optogenetically and pharmacologically controlled 5HT signalling. These experiments aim to understand the serotonergic transmission and intrinsic properties within the PFC involved in WM formation, maintenance and deficiency. Better understanding of these mechanisms will help to develop new and specific therapeutic targets for WM deficiencies.

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