Disruption of retinogeniculate afferent segregation by antagonists to NMDA receptors

Abstract

AFFERENT activity has an important role in the formation of connections in the developing mammalian visual system^1,2. But the extent to which the activity of target neurons shapes patterns of afferent termination and synaptic contact is not known. In the ferret's visual pathway, retinal ganglion cell axons from each eye segregate early in development into eye-specific laminae in the lateral geniculate nucleus (LGN)³. The dorsal laminae (termed laminae A and Al) then segregate further into inner and outer sublaminae that retain input from on-centre and off-centre retinal axons, respectively^4,5. Thus, individual retinogeniculate axons form terminal arbors within laminae A and Al that are restricted to one inner or outer sublamina⁶. We report here that blockade of N-methyl-D-aspartate (NMDA) receptors on LGN cells with specific antagonists during the period of sublamina formation prevents retinal afferents from segregating into 'On' and 'Off sublaminae. Retinogeniculate axons have arbors that are not restricted appropriately, or are restricted in size but inappropri-ately positioned within the eye-specific laminae. NMDA receptor antagonists may specifically disrupt a mechanism by which LGN neurons detect correlated afferent and target activity⁷, and have been shown to reduce retinogeniculate transmission more generally^8–10, causing LGN cells to have markedly reduced levels of activity. These results therefore indicate that the activity of postsynaptic cells can significantly influence the patterning of inputs and the structure of presynaptic afferents during development.