The sequence of formation and development of corticostriate connections in mice

We examined the development of the corticostriate pathway in mice by labeling corticofugal axons with the carbocyanine dye 1, 1'-dioctadecyl-3,3,3'-3'-tetramethylindocarbocyanine perchlorate (DiI). Growth cones of corticofugal axons enter the developing striatum on embryonic day 12 (E12; conception is on E0). By E15 corticofugal axons pass through the developing striatum in the internal capsule but do not produce striatal collaterals. Corticostriate collaterals are seen for the first time on E18, 6 days after the earliest arriving axons enter the striatum. At that time, presumptive synaptic contacts form between cortical axons and striatal neurons. Corticostriate collaterals arise from corticofugal axon trunks at or near axonal varicosities. Primitive corticostriate arbors form by postnatal day 2 (P2; day of birth is P0) and develop further by P7. Thus, corticostriate connections develop in three morphologically defined stages: first cortical axons elongate through the striatum to other subcortical targets, next they produce striatal collaterals, and finally they elaborate terminal arbors. The transition from elongation to collateralization stage may be triggered, among other factors, by signals from striatal neurons relayed via the synaptic contacts.