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PIANISM SIGNED

Prefrontal Cortex Circuit Dynamics underlying Working Memory and its Serotonin Modulation

Total Cost €

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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.

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

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

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 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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