Focus on the axon: from neuronal development to dynamic synapses

Abstract

Neurons acquire an optimized structure for the reception and processing of information, with long protrusions extending from the neuronal cell body. These protrusions are morphologically and functionally different from each other, and are crucial for the establishment of a dynamic and intricate neuronal network. The axon is a long protrusion responsible for the transmission of electrochemical signals to other neurons, while dendrites receive these signals. The propagation of information from the axon of one neuron to the dendrite of another happens at specialized regions called synapses. When a signal travels along the axon and reaches the presynapse, it induces the fusion of synaptic vesicles with the plasma membrane in the presynaptic terminal, releasing neurotransmitters. These neurotransmitters can bind to receptors present at the postsynaptic membrane of the receiving neuron, generating a signal that can be transmitted to the next neuron. To ensure the accurate communication between neurons, synapses must be correctly assembled during development and supplied with specific proteins to the pre- and postsynaptic compartments. As most of the proteins are synthesized in the cell body, they need to be transported to the proper location by motor proteins, which use the underlying actin and microtubule cytoskeleton as rails. The axon extends considerably from the soma to reach the appropriate synaptic partners, and the molecular mechanisms underlying this process have intrigued many neuroscientists. We can study axon development in a controlled environment by culturing neurons from rodent brains. In this system, the axon is formed within the first 24 hours after plating, and the factors that support axon development and outgrowth have to be delivered by motor proteins to the proper location. We have addressed the role of motor proteins in the extension of the axon in hippocampal neurons. Besides their role in axonal outgrowth, we showed that motor proteins are also required for the maintenance of synapses along the dendrites of hippocampal neurons. The presynaptic terminals are very dynamic structures, appearing, disappearing and reappearing at the same location along the axon. Inhibitory presynaptic boutons have been shown to be particularly dynamic, but the molecular mechanisms underlying these dynamics are not understood. In this thesis, we studied a new regulatory pathway of inhibitory presynaptic bouton dynamics triggered by the guidance protein Semaphorin4D.