Functional specificity of local synaptic connections in neocortical networks

Making sense of connectivity In the sensory cortex, neurons are densely interconnected, but the logic by which functionally similar and dissimilar neurons are wired together is an open question. This technical tour de force combines in vivo two-photon calcium imaging and simultaneous whole-cell recording of multiple cells to show that neurons with similar stimulus preferences connect at higher rates than those with dissimilar preferences. This points to the existence of fine-scale sub-networks dedicated to processing related sensory information. Application of this new technique more widely should reveal more about how circuits supporting different sensory or motor functions are constructed in the brain. Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli 1 , 2 , 3 , 4 . But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro , the response properties of which were first characterized in mouse visual cortex in vivo . We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.