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BBB seminar: Clifford Kentros

Genetic interrogation of the neural circuitry of memory

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Clifford Kentros
Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology (NTNU), Trondheim

The brain is the most anatomically complex structure known, composed of hundreds of millions of neurons each connected to thousands of others. Understanding how neural circuits function in both the normal and pathological state requires having access to their individual components, the myriad neuronal cell types, but very few molecular tools have the requisite specificity for this. The Kentros lab addresses this problem by using components (i.e. enhancers) of the genetic machinery underlying this diversity to create synthetic promoters capable of driving transgene expression specific to particular neuronal cell types in both transgenic and viral models. In 2020, we began to use these tools to investigate the role of individual elements of the hippocampal/entorhinal cortex circuit via both electrophysiology and calcium imaging. We also greatly expanded our efforts on Alzheimer’s Disease (AD), developing a new rodent model which captures the pathological interactions between ab and tau, the two main pathological components of AD, in the same entorhinal cortex cells which first show the tauopathy side of AD. We will use this model to study how the interactions between ab and tau cause neurodegeneration specifically in entorhinal neurons, the proximal cause of dementia in AD.

Chairperson: Clive Bramham, Department of Biomedicine