Input to layer 1 of somatosensory cortex: Local input outweighs long-range and can modulate the activity of layer 1 interneurons

Neocortical layer (L) 1 is a locus for interactions between long-range inputs, L1 interneurons and apical tuft dendrites of pyramidal neurons. Even though we have a wealth of information about L1, the level and effect of local input to this layer have not been quantified. Here we characterized the input to L1 of mouse somatosensory cortex with fast blue, monosynaptic rabies and optogenetics. Our work shows that most of the input to L1 is local, and that both local and long-range inputs to this layer arise predominantly from L2/3 and L5 neurons. Subtypes of L5 and L6b neurons project to the overlying L1 with different probabilities. VIP and SST interneurons in L2/3 and L5 also innervate L1. A subset of local L5, the intratelencephalic, pyramidal neurons, drive L1 interneurons but have no effect on L5 apical tuft dendrites. Monosynaptic rabies-based retrograde labelling reveals presynaptic boutons covering the entire somato-dendritic axis of pyramidal neurons, including in L1. When fast blue application was combined with rabies virus, we found that only a fraction of local and long-range neurons was both presynaptic to L5 neurons and projected to L1. These results demonstrate that L1 receives a large proportion of its input from local neurons, and that some of these inputs specifically target interneurons. We conclude that L1 is not just a site for interaction between long-range feedback and apical tuft dendrites of pyramidal cells, it is also a site for complex modulation of pyramidal neurons and interneurons by local inputs.Here we used traditional retrograde tracing combined with physiology and rabies virus to quantify the connectivity to L1 of somatosensory cortex. We show that local inputs far outweigh long-range inputs. We also show that subtypes of L5 neurons target the overlying L1 and depolarize L1 interneurons but have little effect on the apical tuft dendrites of L5 neurons. Local and long-range cortical inputs to L1 arise from presynaptic neurons in L2/3 and L5. The long-range input arises from a variety of cortical areas including primary motor, secondary somatosensory and motor, perirhinal and visual cortex. Thus, interneurons in L1 and the dendrites of pyramidal neurons are the site of complex interactions with local and long-range inputs.

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