MECEDGE · Transgenic dissection of the neural circuitry of memory and dementia
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-05-01 → 2020-11-29
- EU contribution
- €196,400
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Transgenic dissection of the neural circuitry of memory and dementia
As the most common form of age-related dementia, Alzheimer's disease (AD) is an enormous and growing problem for an aging society. AD is a neurodegenerative disorder like Parkinson's disease (PD), but the former presents as a cognitive disorder, and the latter as a motor disorder (at least in early stages). The reason for this is not so much what happens (ultimately cell death in both cases), but *where* it happens (respectively, the entorhinal cortex, or EC, or the substantia nigra). This project attempts to explore what is it about the EC that makes it particularly susceptible to the pathological processes underlying AD, with particular emphasis on the role of activity. To do this, we combine transgenic lines we have created which allow us to manipulate the activity of neurons in this region with transgenic models of AD, and record the effects on both activity and AD-like phenotypes.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU · TrondheimCoordinatorNorway
Links
Data: CORDIS, © European Union