Development of visual cortical axons: layer-specific effects of extrinsic influences and activity blockade

During normal cortical development, individual pyramidal neurons form intracortical axonal arbors that are specific for particular cortical layers. Pyramidal neurons within layer 6 are able to develop layer-specific projections in cultured slices of ferret visual cortex, indicating that extrinsic influences, including patterned visual activity, are not required (Dantzker and Callaway [1998] J Neurosci 18:4145-4154). However, when spontaneous activity is blocked in cultures with tetrodotoxin, layer 6 pyramidal neurons fail to preferentially target their axons to layer 4. To determine whether mechanisms that regulate the development of layer 6 pyramidal neuron arbors can be generalized to pyramidal neurons in other layers, we examined the development of layer 5 and layer 2/3 pyramidal neurons in cultured slices of ferret visual cortex prepared on postnatal day 14 or 15. Layer 5 pyramidal neurons developed layer-specific axonal arbors during 5-7 days in vitro. However, unlike layer 6 pyramidal neurons, layer 5 pyramidal neurons formed layer-specific axonal arbors in the presence of tetrodotoxin. In contrast to layer 5 and layer 6 pyramidal neurons, layer 2/3 pyramidal neurons did not form appropriate layer-specific projections during 5-7 days in vitro. Taken together, these data suggest that the development of layer-specific axons is regulated by different mechanisms for neurons in different layers and cannot be categorically classified as either activity-dependent or independent. Instead, the type of pyramidal neuron, the layers targeted, and the type of activity must be considered.