Elucidation of the physiological role of BARP, a new blocker of voltage-gated Ca2+ channels,in Purkinje cell

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The aim of this aborted project was to determine the contribution of a newly identified regulator of calcium channels, in neuronal synaptic plasticity. The regulator, named cBARP is highly expressed in some pyramidal neurons and in cerebellar Purkinje cells. In the initial phase of the project, the main investigator developed in parallel a Purkinje-specific inducible over-expression and a microRNA-based silencing strategy, to examine the contribution of this protein to calcium homeostasis in neurons. Concomitantly, though a collaboration with colleagues at A*Star (Singapore), we started to utilize a new conditional cBARP-KO transgenic mice, for specifically altering cBARP expression in Purkinje neuron, in vivo. The results obtained indicate that cBARP is a strong regulator of voltage-dependent calcium channels in neurons and profoundly affects neuronal development if expression is induced at early post-natal stage in neurons. The MiRNA-based silencing construct and strategy using recombinase-based conditional KO only showed moderate reduction of cBARP expression in the targeted neurons, far lower than the results previously obtained in test models. This may indicates a peculiar stability of cBARP (low turn-over) in Purkinje cells. The unfortunate disease and passing-away of Dr. Beguin changed the focus of the project from a long-term effort to one to be completed within the first half of FY2017.