Master project - Thalamocortical astrocyte dysfunction in Alzheimer’s disease
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that is characterised by progressive cognitive decline and a prominent loss of hippocampal-dependent memory. However, AD is also accompanied by a number of other debilitating cognitive and behavioural alterations, which occur early in disease progression, including deficits in attention and sensory processing.
Critical to sensory processing, are the neural networks connecting the thalamus to the cerebral cortex (the thalamocortical system). Rather than being static, these networks are highly dynamic and modifiable on a moment-to-moment basis depending on behavioural demand. Recently, we have uncovered exciting data suggesting that thalamocortical networks may be one of the main sites involved in the early sensory alterations in AD.
The main objective of this project is to understand how astrocytes, the major glial cell in the brain, regulates thalamocortical activity and the subsequent processing of sensory information. Specifically, the student will investigate state-dependent astrocytic IP3R2-dependent Ca2+ signalling during complex behaviours (see figure below), over the progression of Alzheimer’s disease.
This project will use an all-optical approach (including transcranial imaging and/or fiber photometry) to assess behaviourally-relevant thalamocortical network dynamics and state-dependent processing of sensory stimuli by astrocytes over the lifespan of transgenic mice predisposed to developing AD pathology.
The findings from this project will be an important step in defining new and more effective diagnostic and therapeutic strategies against debilitating neurodegenerative diseases.
If you are interested in this project, and want to learn more, please contact Postdoc, Andy Samson, at the Center for Translational Neuromedicine, at andy.samson@sund.ku.dk