Novel insights into neuronal CAMK2 function
Nieuwe inzichten in de functie van neuronaal CAMK2
CAMK2A and CAMK2B are amongst the most abundant proteins in the brain and crucial for learning and memory. Recently, individuals with severe intellectual disability carrying mutations in the genes coding for CAMK2A or CAMK2B have been identified, emphasizing the role of CAMK2 in learning and memory in human. In this thesis the individual as well as the shared role of CAMK2A and CAMK2B in learning and memory is investigated using conditional knockout mouse models, where CAMK2A or CAMK2B can be deleted with spatial and/or temporal precision. First, we tested the spatiotemporal requirement of CAMK2A for spatial learning and plasticity, showing the necessity for CAMK2A expression at the moment of learning and LTP induction. Second, we tested the spatiotemporal requirement of CAMK2B in locomotion, finding an important role for CAMK2B during development. Third, we assessed the shared role of CAMK2A and CAMK2B and found that not only absence, but also loss of kinase activity of both proteins simultaneously leads to premature death. Finally, we found that at the level of a single neuron, loss of both CAMK2A and CAMK2B results in changes in excitability and loss of neuronal input. Together, this thesis further elucidates the function of CAMK2 at the behavioural level, the network level and the single cell level. Understanding these functions will provide new insights for finding therapies for patients with intellectual disability caused by mutations in one of the CAMK2 genes.
|Keywords||CAMK2, hippocampus, memory, learning, CAMK2A, CAMK2B, Electrophysiology, Field Electrophysiology, Ca2+-dependent protein kinase II, LTP|
|Promotor||Y. Elgersma (Ype) , G.M. van Woerden (Geeske)|
|Publisher||Erasmus University Rotterdam|
Kool, M.J. (2018, December 11). Novel insights into neuronal CAMK2 function. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/113153