Neurotrophin-3 is required for appropriate establishment of thalamocortical connections

In the vertebrate brain, the thalamus serves as a relay and integration station for diverse neuronal information en route from the periphery to the cortex. Formation of the thalamocortical tract occurs during pre- and postnatal development, with distinct thalamic nuclei projecting to specific cortical regions. The molecular forces that underlie the invasion by axons into specific cortical layers followed by activity-dependent maturation of synapses are poorly understood. We show that genetic ablation of neurotrophin-3 (NT-3) in the mouse neocortex results in reduction of a set of anatomically distinct axonal bundles projecting from thalamus through cortical white matter. These bundles include thalamocortical axons that normally establish connections with retrosplenial and visual cortex, sites of early postnatal NT-3 expression. These results implicate neurotrophins in the critical stage of precise thalamocortical connections.