Single neurons and networks in the claustrum integrate input from widespread cortical sources

The claustrum is highly interconnected with many structures in the brain, but the organizing principles governing its vast connectivity have yet to be fully explored. We investigated the defining characteristics and activity of single claustrum neurons, the nature of their relationship with the cortex, and their connectivity within the claustrum itself to gain a comprehensive view of claustral circuits. We show that the claustrum is composed of excitatory and inhibitory cell types that are connected through intraclaustral excitatory synapses, especially between neurons with disparate projection targets. Investigations of corticoclaustral innervation demonstrated that axons from the cortex localize to distinct dorsoventral modules depending on their region of origin.In vitrodual-color optogenetic mapping experiments revealed that individual claustrum neurons integrated inputs from more than one cortical region in a cell type- and projection target-specific manner. Integration in claustrum neurons was observed to be particularly common between areas of the frontal cortex and less so for sensory, motor, and association cortices. Finally, activity in claustrum axons in midline cortical areas recorded within vivotwo-photon calcium imaging showed responses to multimodal sensory stimuli. Our findings shed light on the organizing principles of claustrum circuits, demonstrating that individual claustrum neurons integrate cortical inputs and redistribute this information back to cortex after performing output target- and cell type-dependent local computations.