The effect of Amyloid-β and tau proteins on the hippocampal neural networks and animal’s ability to navigate
Project ID: NMH30
Supervisor: Dr. Julija Krupic
Web page: https://www.krupiclab.com/
Alzheimer’s disease (AD) has been identified as the leading cause of dementia with millions of people affected worldwide. Post-mortem studies of human brains with AD revealed extensive neuronal degeneration primarily in the entorhinal cortex and hippocampus, the areas crucial for memory and learning. In addition neuronal loss was also correlated with accumulation of amyloid‑β plaques and tau neurofibrillary tangles. Currently it is unclear how these processes are related as these observations reflect the later stages of AD when many structural and biochemical changes have already taken place. Here we propose to use a mouse model of AD to study its progression from the onset to neuronal loss and behavioural deficits. We will use in vivo two photon imaging in head-fixed mice navigating in virtual reality to study the changes in neural activity in the hippocampal formation and their relation to the accumulation of tau and Amyloid-β proteins. We will also correlate these changes to decline of an animal’s cognitive performance. We will develop new behavioural assays sensitive to different stages of AD. This will lead to the development of an early diagnosis methods and ultimately more effective treatments. We will use optogenetics as well as pharmacological manipulations of the hippocampal neural networks aiming to interfere with the progression of the disease before neural loss and cognitive decline has taken place.
During this project we will aim to develop a fully automated home cage to characterize the changes in different types of behaviour (e.g. cognitive and motor behaviours) in mouse models of AD. The aim is to translate this to a wider use to enable a high throughput screen for emerging behavioural impairments from their onsets and screen of possible treatment methods (pharmacological and others) for effective early intervention methods.