Molecular mechanisms of the functional and structural maintenance of the synapse.
The synapses are the points of contact where neuronal communication takes place that underlies the correct operation of the brain. The nerve endings house synaptic vesicles loaded with neurotransmitters that are released after the arrival of a nerve impulse. This phenomenon can occur thousands of times a day in terminals that are very remote from the neuronal body, as in the case of motor neurones. The nerve endings probably have molecular machinery that allows them to maintain synaptic function independently of the neuronal body. Our laboratory is interested in identifying the components of this machinery and in understanding their mode of operation. A key element is a protein of the synaptic vesicles called Cysteine String Protein-alpha (CSP-alpha). This protein is related to molecular chaperones that participate in the folding and unfolding of proteins. Strangely, genetically modified mice that lack this protein display a neurological phenotype produced by an early degeneration of their nerve endings. Our laboratory uses cultivated neurons from these mice, that form synapses "in vitro" and we study the details of the neuronal communication by means of electro-physiological techniques. In collaboration with the Center of Animal Production and Experimentation of the University of Seville, we have generated transgenic mice that express a green fluorescent protein (synaptopHluorin) that illuminates the nerve endings during synaptic activity. These approaches will be used to understand the functional modifications of the synapse that precede the neurodegeneration of the neurons of the central and peripheral nervous system.