LAYER-SPECIFIC PROGRAMS OF DEVELOPMENT IN NEOCORTICAL PROJECTION NEURONS

How are long-range axonal projections from the cerebral Cortex orchest rated during development? By using both passively and actively transpo rted axonal tracers in fetal and postnatal ferrets, we have analyzed t he development of projections from the cortex to a number of thalamic nuclei. We report that the projections of a cortical area to its corre sponding thalamic nuclei follow highly cell-specific programs of devel opment, Axons from cells in the deepest layers of the cerebral cortex (layer 6 and superficial subplate neurons) appear to grow very slowly and be delayed for several weeks in the cerebral white matter, reachin g the thalamus over a protracted period, Neurons of layer 5, on the ot her hand, develop their projections much faster; despite being born af ter the neurons of deeper layers, layer 5 neurons are the first to ext end their axons out of the cortical hemisphere and innervate the thala mus, Layer 5 projections are massive in the first postnatal weeks but may become partly eliminated later in development, being overtaken in number by layer 6 cells that constitute the major corticothalamic proj ection by adulthood. Layer 5 projections are area-specific from the ou tset and arise as collateral branches of axons directed to the brainst em and spinal cord. Our findings show that the early development of co rticofugal connections is determined not by the sequence of cortical n eurogenesis but by developmental programs specific for each type of pr ojection neuron, In addition, they demonstrate that in most thalamic n uclei, layer 5 neurons (and not subplate or layer 6 neurons) establish the first descending projections from the cerebral cortex.