The neurons of layer 4 in the adult cerebral cortex receive their major ascending inputs from the thalamus. In development, however, thalamic axons arrive at the appropriate cortical area long before their target layer 4 neurons have migrated into the cortical plate. The axons accumulate and wait in the zone below the cortical plate, the subplate, for several weeks before invading the cortical plate. The subplate is a transient zone that contains the first postmitotic neurons of the telencephalon. These neurons mature well before other cortical neurons, and disappear by cell death after the thalamic axons have grown into the overlying cortical plate. The close proximity of growing thalamocortical axons and subplate neurons suggests that they might be involved in interactions important for normal thalamocortical development. Here we show that early in development the deletion of subplate neurons located beneath visual cortex prevents axons from the lateral geniculate nucleus of the thalamus from recognizing and innervating visual cortex, their normal target. In the absence of subplate neurons, lateral geniculate nucleus axons continue to grow in the white matter past visual cortex despite the presence of their target layer 4 neurons. Thus the transient subplate neurons are necessary for appropriate cortical target selection by thalamocortical axons.

If vision in one eye is blurred or occluded during a critical period in postnatal development, neurons in the visual cortex lose their responses to stimulation through that eye within a few days. Anatomical changes in the nerve terminals that provide input to the visual cortex have previously been observed only after weeks of deprivation, suggesting that synapses become physiologically ineffective before the branches on which they sit are withdrawn. Reconstruction of single geniculocortical axonal arbors in the cat after either brief or prolonged monocular occlusion revealed striking axonal rearrangements in both instances. Rapid withdrawal of the branches of deprived-eye arbors suggests that axonal branches bearing synapses respond quickly to changing patterns of neuronal activity.

Much of what is known about activity-dependent plasticity comes from studies of the primary visual cortex and its inputs in higher mammals, but the molecular bases remain largely unknown. Similar functional plasticity takes place during a critical period in the visual cortex of the mouse, an animal in which genetic experiments can readily be performed to investigate the underlying molecular and cellular events. The experiments of this paper were directed toward understanding whether anatomical changes accompany functional plasticity in the developing visual cortex of the mouse, as they do in higher mammals. In normal mice, transneuronal label after an eye injection clearly delineated the monocular and binocular zones of area 17. Intrinsic signal optical imaging also showed monocular and binocular zones of area 17 but revealed no finer organization of ocular dominance or orientation selectivity. In normal animals, single geniculocortical afferents serving the contralateral eye showed great heterogeneity and no clustering consistent with the presence of ocular dominance patches. Growth and elaboration of terminal arbor continues beyond postnatal day 40 (P40), after the peak of the critical period. After prolonged monocular deprivation (MD) from P20 to P60, transneuronal labeling showed that the projection serving the ipsilateral eye was severely affected, whereas the effect on the contralateral eye's pathway was inconsistent. Optical imaging also showed profound effects of deprivation, particularly in the ipsilateral pathway, and microelectrode studies confirmed continued functional plasticity past P40. Reconstruction of single afferents showed that MD from P20 to P40 promoted the growth of the open eye's geniculocortical connections without causing the closed eye's contralateral projection to shrink, whereas MD from P20 to P60 caused an arrest of growth of deprived arbors. Our findings reveal numerous similarities between mouse and higher mammals in development and plasticity, along with some differences. We discuss the factors that may be responsible for these differences.