THE SEQUENCE OF FORMATION AND DEVELOPMENT OF CORTICOSTRIATE CONNECTIONS IN MICE

We examined the development of the corticostriate pathway in mice by l abeling corticofugal axons with the carbocyanine dye 1, -dioctadecyl-3 ,3,3'-3'-tetramethylindocarbocyanine perchlorate (DiI). Growth cones o f corticofugal axone enter the developing striatum on embryonic day 12 (E12; conception is on EO), By E15 corticofugal axons pass through th e developing striatum in the interval capsule but do not produce stria tal collaterals. Corticostriate collaterals are seen for the first tim e on E18, 6 days after the earliest arriving axons enter the striatum. At that time, presumptive synaptic contacts form between cortical axo ns and striatal neurons. Corticostriate collaterals arise from cortico fugal axon trunks at or near axonal varicosities. Primitive corticostr iate arbors form by postnatal day 2 (P2; day of birth is PO) and devel op further by P7. Thus, corticostriate connections develop in three mo rphologically defined stages: first cortical axons elongate through th e striatum to other subcortical targets, next they produce striatal co llaterals, and finally they elaborate terminal arbors. The transition from elongation to collateralization stage may be triggered, among oth er factors, by signals from striatal neurons relayed via the synaptic contacts.