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The visual cortex is organized into retinotopic maps that preserve an orderly representation of the visual world, achieved by topographically precise inputs from the lateral geniculate nucleus. We show here that geniculocortical mapping is imprecise when the waves of spontaneous activity in the retina during the first postnatal week are disrupted genetically. This anatomical mapping defect is present by postnatal day 8 and has functional consequences, as revealed by optical imaging and microelectrode recording in adults. Pharmacological disruption of these retinal waves during the first week phenocopies the mapping defect, confirming both the site and the timing of the disruption in neural activity responsible for the defect. Analysis shows that the geniculocortical miswiring is not a trivial or necessary consequence of the retinogeniculate defect. Our findings demonstrate that disrupting early spontaneous activity in the eye alters thalamic connections to the cortex.

Ephrin-As and their receptors, EphAs, are expressed in the developing cortex where they may act to organize thalamic inputs. Here, we map the visual cortex (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic signal optical imaging and microelectrode recording, and structurally, by anatomical tracing of thalamocortical projections. V1 is shifted medially, rotated, and compressed and its internal organization is degraded. Expressing ephrin-A5 ectopically by in utero electroporation in the lateral cortex shifts the map of V1 medially, and expression within V1 disrupts its internal organization. These findings indicate that interactions between gradients of EphA/ephrin-A in the cortex guide map formation, but that factors other than redundant ephrin-As are responsible for the remnant map. Together with earlier work on the retinogeniculate map, the current findings show that the same molecular interactions may operate at successive stages of the visual pathway to organize maps.

During a critical period of brain development, occluding the vision of one eye causes a rapid remodeling of the visual cortex and its inputs. Sleep has been linked to other processes thought to depend on synaptic remodeling, but a role for sleep in this form of cortical plasticity has not been demonstrated. We found that sleep enhanced the effects of a preceding period of monocular deprivation on visual cortical responses, but wakefulness in complete darkness did not do so. The enhancement of plasticity by sleep was at least as great as that produced by an equal amount of additional deprivation. These findings demonstrate that sleep and sleep loss modify experience-dependent cortical plasticity in vivo. They suggest that sleep in early life may play a crucial role in brain development.

The significance of functional maps for cortical plasticity was investigated by imaging of intrinsic optical signals together with single-unit recording in kittens. After even a brief period of monocular deprivation during the height of the critical period, only isolated patches of visual cortex continued to respond strongly to the closed eye. These deprived-eye patches were located on the pinwheel center singularities of the orientation map and consisted of neurons that were poorly selective for stimulus orientation. Neurons in regions surrounding the deprived-eye patches responded only weakly to the deprived eye but were well tuned for the same stimulus orientation that optimally excited them when presented to the open, nondeprived eye. The coincidence of deprived-eye patches with pinwheel center singularities, and the selective loss of orientation tuning within the deprived-eye patches, indicate that the orientation and ocular dominance maps are functionally linked and provide compelling evidence that pinwheel center singularities are important for cortical plasticity.