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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.

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

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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