Spontaneous retinal waves generate long-range horizontal connectivity in visual cortex

In the primary visual cortex (V1) of higher mammals, long-range horizontal connections (LHCs) are observed to develop, linking iso-orientation domains of cortical tuning. It is unknown how this feature-specific wiring of circuitry develops before eye opening. Here, we show that LHCs in V1 may originate from spatio-temporally structured feedforward activities generated from spontaneous retinal waves. Using model simulations based on the anatomy and observed activity patterns of the retina, we show that waves propagating in retinal mosaics can initialize the wiring of LHCs by co-activating neurons of similar tuning, whereas equivalent random activities cannot induce such organizations. Simulations showed that emerged LHCs can produce the patterned activities observed in V1, matching topography of the underlying orientation map. We also confirmed that the model can also reproduce orientation-specific microcircuits in salt-and-pepper organizations in rodents. Our results imply that early peripheral activities contribute significantly to cortical development of functional circuits. Highlights Developmental model of long-range horizontal connections (LHCs) in V1 is simulated Spontaneous retinal waves generate feature-specific wiring of LHCs in visual cortex Emerged LHCs induce orientation-matching patterns of spontaneous cortical activity Retinal waves induce orientation-specific microcircuits of visual cortex in rodents Significance statement Long-range horizontal connections (LHCs) in the primary visual cortex (V1) are observed to emerge before the onset of visual experience, selectively connecting iso-domains of orientation maps. However, it is unknown how such tuning-specific wirings develop before eye-opening. Here, we show that LHCs in V1 originate from the tuning-specific activation of cortical neurons by spontaneous retinal waves during early developmental stages. Our simulations of a visual cortex model show that feedforward activities from the retina initialize the spatial organization of activity patterns in V1, which induces visual feature-specific wirings of V1 neurons. Our model also explains the origin of cortical microcircuits observed in rodents, suggesting that the proposed developmental mechanism is applicable universally to circuits of various mammalian species.