Open Access

Lisa Kochen

• The information flow between neurons happens at contact points, the synapses. One underlying mechanism of learning and memory is the change in the strength of information flow in selected synapses. In order to match the huge demand in membranes and proteins to build and maintain the neurites' complex architecture, neurons use decentralized protein synthesis. Many candidate proteins for local synthesis are known, and the need of de novo synthesis for memory formation is well established. The underlying mechanisms of how somatic versus dendritic synthesis is regulated are yet to be elucidated. Which proteins are newly synthesized in order to allow learning? In this thesis protein synthesis is studied in hippocampal neurons. The fractional distribution of somatic and dendritic synthesis for candidate proteins and their subsequent transport to their destination are investigated using a newly developed technique. In the first part of this study we describe the development of this technique and use it in the second part to answer biological questions. We focus here on AMPA receptor subunits, the key players in fast excitatory transmission. AMPA receptors contain multiple subunits with diverse functions. It remains to be understood, when and where in a neuron these subunits come together to form a protein complex and how the choice of subunits is regulated. The investigation of the subunits' site of synthesis and redistribution kinetics in this study will help us to understand how neurons are able to change their synaptic strength in an input specific manner which eventually allows learning and memory. Key questions which are addressed in this study: How can specific newly synthesized endogenous proteins be visualized in situ? What are the neuron's abilities to locally synthesize and fully assemble AMPA receptor complexes? How fast do different AMPA receptor subunits redistribute within neurons after synthesis?