Transgenic dissection of the neural circuitry of memory and dementia

Información del proyecto

MECEDGE

Identificador del acuerdo de subvención: 796535

DOI

10.3030/796535

Proyecto finalizado el 21 Noviembre 2018

Fecha de la firma de la CE 6 Marzo 2018

Fecha de inicio 1 Mayo 2018

Fecha de finalización 29 Noviembre 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 196 400,40

Aportación de la UE

€ 196 400,40

Coordinado por

NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Norway

Objetivo

Our memories are arguably what make us who we are, making dementia a particularly cruel disease. Decades of research have revealed that two interconnected brain regions, the medial entorhinal cortex (MEC) and hippocampus (HP), are required for successful spatial memory formation in mammals. Each region contains specialized neurons that fire relative to the animal`s position in physical space: grid cells in the MEC have regularly-repeating spatial firing fields throughout the entire environment (“grid field”); and place cells in the CA1 region of the HP fire at a particular location within an environment (“place field”). Spatial information from the MEC grid cells reaches CA1 place cells in two ways: through an (1) indirect pathway (IP) via layer II MEC neurons, or a (2) direct pathway (DP) via the layer III MEC neurons. Thus, hippocampal neurons compare processed and unprocessed input. However, the relative roles of these two kinds of input onto hippocampal firing patterns remains elusive, largely due to the difficulty in performing layer-specific manipulations. The Kentros lab at NTNU has developed a novel and exciting genetic technology that makes such experiments possible. Therefore, I propose to conduct in vivo electrophysiological recordings in CA1 while manipulating the DP to determine the effects of direct MEC input on hippocampal network dynamics. I will then investigate the behavioral ramifications of manipulating the DP on spatial task performance. Interestingly, the superficial layers of entorhinal cortex are the first brain area to exhibit the pathological signs of Alzheimer`s Disease (AD) in patients. Therefore, I will compare the relative roles of entorhinal layer II and III neuron activity in the progression of pathology in a preclinical mouse model of AD. Thus, this proposal will provide insight into how the distinct circuit elements of the entorhinal cortex contribute to place field formation, memory performance, and disease progression.

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › medicina básica › neurología › demencia › alzheimer
• ciencias médicas y de la salud › medicina básica › patología
• ciencias naturales › ciencias biológicas › zoología › mamalogía
• ciencias médicas y de la salud › medicina básica › neurología › parkinson

Palabras clave

• place cells
• hippocampus
• medial entorhinal cortex
• chemogenetics
• enhancers
• transgenics
• Alzheimer`s Disease

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2017 - Individual Fellowships
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2017

Coordinador

NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU

• Aportación neta de la UEn: € 196 400,40
• Dirección: HOGSKOLERINGEN 1 ; 7491 TRONDHEIM ; Noruega
• Región: Norge › Trøndelag › Trøndelag
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 196 400,40