Thalamocortical axons are influenced by chemorepellent and chemoattractantactivities localized to decision points along their path

Thalamocortical axons (TCAs), which originate in dorsal thalamus, project v entrally in diencephalon and then dorsolaterally in ventral telencephalon t o their target, the neocortex. To elucidate potentially key decision points in TCA pathfinding and hence the possible localization of guidance cues, w e used DiI-tracing to describe the initial trajectory of TCAs in mice. DiI- labeled TCAs extend ventrally on the lateral surface of ventral thalamus. R ather than continuing this trajectory onto the lateral surface of the hypot halamus, TCAs make a sharp lateral turn into ventral telencephalon. This be havior suggests that the hypothalamus is repulsive and the ventral telencep halon attractive for TCAs. In support of this hypothesis, we find that axon outgrowth from explants of dorsal thalamus is biased away from hypothalamu s and toward ventral telencephalon when cocultured at a distance in collage n gels. The in vivo DiI analysis also reveals a broad cluster of retrograde ly labeled neurons in the medial part of ventral telencephalon positioned w ithin or adjacent to the thalamocortical pathway prior to or at the time TC As are extending through it. The axons of these neurons extend into or thro ugh dorsal thalamus and appear to be coincident with the oppositely extendi ng TCAs. These findings suggest that multiple cues guide TCAs along their p athway from dorsal thalamus to neocortex: TCAs may fasciculate on the axons of ventral telencephalic neurons as they extend through ventral thalamus a nd the medial part of ventral telencephalon, and chemorepellent and chemoat tractant activities expressed by hypothalamus and ventral telencephalon, re spectively, may cooperate to promote the turning of TCAs away from hypothal amus and into ventral telencephalon. (C) 1999 Academic Press.