Topographic projection is a general feature of brain architecture and is critical for appropriate information processing and coding. Nevertheless, little is known about the mechanisms that govern topographic organization. Among the many regions exhibiting topographic relations, the limbic system has been the focus of intense interest, since it plays key roles in learning, memory, and motivated behavior. The Eph family receptor tyrosine kinases and ligands have been recently implicated in the specification of topographic maps. We have shown that Eph family receptors and ligands are expressed in complementary fashion in neurons and targets, respectively, in several regions of the limbic system. For example, in the hippocampus, the Eph receptor Bsk is expressed in an increasing lateral to medial gradient. In contrast, at least three different ligands, Elf-1, LERK3/Ehk1-L, and AL-1/RAGS/LERK7, are transcribed in complementary (opposing) gradients in the hippocampal subcortical target, the lateral septum. However, the spatial and temporal distribution of the ligands are different such that combinatorially they form a smooth dosromedial to ventrolateral gradient in the lateral septum, specifying the full target region during development. Consistent with a key role in hippocamposeptal topographic projection, the ligands selectively inhibit the growth of the topographically inappropriate medial hippocampal neurites but sustain the growth of correct lateral neurites. Our studies indicate that the inhibitive interaction of Bsk and its ligands restrict the receptor-positive medial neurons to the topographically appropriate, ligand-poor dorsal septal target. In addition to the hippocamposeptal system, BSK and its ligands are also expressed in afferents and targets of neurons from several other regions of the limbic system, including neurons in the mesolimbic pathway, which arises from the ventral tegmental dopaminergic neurons and terminates in the nucleus accumbens and limbic regions such as the amygdala. These observations indicate that the Eph family molecules play important roles in establishing the limbic neural circuits.

[Abstract Titles] [Anderson] [Bolz] [Chugani] [Levitt] [Olson]