From the outset of Cajal’s studies in 1888, he provided strong support for his belief that dendrites and axons end freely in the nervous system and communicate by contact through the synapses. Thanks to the introduction of transmission electron microscopy in the 1950s, along with the development of methods to prepare nervous tissue for ultrastructural analysis, the nature of synapses was finally examined, confirming that the pre-synaptic and the post-synaptic elements in nervous tissues are physically separated by the synaptic cleft. In this talk, I will summarize the advances in the methods used to map the brain’s synapses. I propose that the best approach to study synaptic connectivity is tolink detailed structural data with light and electron microscopy wiring diagrams, and integrate this information with genetic, molecular and physiological data. This integration will allow formulating new hypotheses and generating models to make predictions about neurodegenerative diseases.
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