Forsøksdyr: Regulation and function of Arc in synaptic plasticity

Godkjenningsdato 08.08.2018

Godkjenningsperiode 08.08.2018-07.08.2022

This study investigates the function of the neuron activity-induced gene, Arc, in
modulation of the synaptic strength and structure in the hippocampus of the adult
rat in vivo. The Arc protein is emerging as possible master regulator synaptic plasticity, memory formation, and cognition. Arc protein is multifunctional, by connecting to many different signaling systems inside the neuron. Genetic mutations in Arc the signanling network are associated with human intelligence and in some case increased risk for neuropsychiatric disorders such as Schizophrenia. This project aims to elucidate the molecular control and function of Arc protein, using rats as a model organism. The project addresses 6 main themes on the regulation of Arc. To approximate functional connectivity in the intact brain, all experiments will be performed in surgically anesthetized rats. In this multi-pronged team effort, we will use approximately 576 rats over the next 4 years. The study is full compliance with the 3Rs - to replace, reduce, and refine. The work in live rats is supported by additional preliminary studies carried out in reduced preparations such as primary neuronal cultures derived from rat embyros. The number of rats per treatment group is kept to the minumum number that will allow us to draw conclusion, and procedures are refined and streamlined to reduce variance in data collection.