"Given the complexity of the neocortex, the need for establishing simplifying principles of connectivity is paramount. Local cortical circuits form stereotyped connections across the neocortex. Within a cortical column, connections show laminar specificity and target preferentially particular cell-types while avoiding others. In addition, subnetworks of highly interconnected neurons are embedded in the local circuit. These subnetworks receive common local input and have similar functional properties in vivo, suggesting the might work as functional units. In contrast to our knowledge of the local circuits, the connectivity of long-range cortical circuits remains largely unknown. Here we propose studying the organization of long-range cortical connections using a combination of optogenetic and electrophysiological methods. By mapping the connections made by genetically-defined neuronal types in local and distant cortical areas we aim at unraveling whether long-range and local connections have the same target specificity. Using channelrhodopsin-2 assisted circuit mapping we will probe the connectivity and subcellular distribution of V1 cortico-cortical projections from Layer(L)2/3 and L5 within V1 and in distant target visual cortical areas. Similarly we want to establish how subnetworks of interconnected neurons connect with inputs from outside their local circuits. We will develop a new optogenetic circuit-mapping method that will allow us assessing whether the interconnected neurons constituting cortical subnetworks receive common long-range connections. Taken as a whole, this proposal will shed light on the connectivity of long-range connections while potentially establishing some simplifying organizational principles underlying cortical connectivity. In addition, the research plan outlined will bring to the Iberian Peninsula and the EU a new set of skills and approaches for studying neural circuits that I developed after extensive training in the USA."