Mitochondrial regulation of structural and functional plasticity within adult neurogenic circuits

Projektinformationen

MITOPLASTICITY

ID Finanzhilfevereinbarung: 677844

DOI 10.3030/677844

Abgeschlossenes Projekt

EK-Unterschriftsdatum 22 April 2016

Startdatum 1 August 2016

Enddatum 31 Juli 2021

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 1 199 987,50

EU-Beitrag € 1 199 987,50

Koordiniert durch

KLINIKUM DER UNIVERSITAET ZU KOELN
Germany

Ziel

A fundamental question in neuroscience is to reveal the energy constrains governing the plasticity of brain circuits. Mitochondrial energy metabolism is increasingly recognized for regulating the activity and integrity of existing synaptic terminals, however it is unclear how changes in mitochondrial function are coupled with the generation of new neurons and the ensuing circuit remodelling, e.g. in response to experience or disease. We have recently shown that a regionalized restructuring of the mitochondrial network in astrocytes upon cortical injury underlies their ability to enter a state of reactivity and sustain cellular energy metabolism, suggesting that local changes in mitochondrial network architecture govern cellular adaptations in register with local metabolic demand. Here, I focus on the adult hippocampal circuitry and its almost unique structural plasticity to broaden this fundamental concept and evaluate whether local mitochondrial remodelling orchestrates the metabolic changes underlying the directed genesis of new neurons and their evolving connectivity in face of experience. First, we will utilize state-of-the-art imaging and genetic techniques to investigate the precise role of mitochondria in regulating adult neural stem cells (NSCs) quiescence, mode of division and neurogenic potential in response to experience. This will set the stage for examining whether state-specific energy metabolism programs regulate the fate plasticity of adult NSCs, as following their directed differentiation towards distinct lineages in vivo (Aim I). We will then elucidate whether mitochondria contribute to mechanisms of metabolic and synaptic competition in new neurons, in particular to their critical period of heightened structural and functional synaptic plasticity (Aim II). Lastly, we will use novel tracing techniques to dissect the local energy needs for activity- and experience-dependent remodelling of new neuron functional connectivity (Aim III).

Wissenschaftliches Gebiet

• natural sciences › biological sciences › neurobiology
• natural sciences › biological sciences › cell biology
• medical and health sciences › medical biotechnology › cells technologies › stem cells
• engineering and technology › environmental engineering › energy and fuels

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-StG-2015 - ERC Starting Grant

Aufforderung zur Vorschlagseinreichung

ERC-2015-STG

Finanzierungsplan

ERC-STG - Starting Grant

Gastgebende Einrichtung

KLINIKUM DER UNIVERSITAET ZU KOELN

• Netto-EU-Beitrag: € 1 199 987,50
• Adresse: Kerpener Strasse 62 ; 50937 Koeln ; Deutschland
• Region: Nordrhein-Westfalen › Köln › Köln, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 1 199 987,50

Begünstigte (1)

KLINIKUM DER UNIVERSITAET ZU KOELN

Deutschland

• Netto-EU-Beitrag: € 1 199 987,50
• Adresse: Kerpener Strasse 62 ; 50937 Koeln
• Region: Nordrhein-Westfalen › Köln › Köln, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 1 199 987,50