Axon Guidance and the Formation of Specific Connections in the Hippocampus

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Abstract
Pathfinding by growing axons towards their appropriate targets is an essential step prior to the formation of specific synaptic connections. Diffusible and membrane-bound molecules are known to exert either a chemoattractive or chemorepellent function on outgrowing axons during the sensitive period of axonal pathfinding. In the hippocampus, extrinsic and intrinsic afferents terminate in a non-overlapping fashion in the various hippocampal laminae. Recent studies using in vitro techniques and knockout animals provide evidence for guiding cues during the development of the hippocampus. These signals are expressed in a well-defined spatio-temporal pattern, indicating their important role for the establishment of the typical layer-specific termination of afferents in the hippocampus. Among the secreted molecules, netrin 1 is specifically involved in the formation of crossed projections in the CNS. Depletion of this gene prevents commissural fibres from crossing the midline towards the developing contralateral hippocampus. Moreover, the altered termination of hippocampal afferents in the dentate gyrus suggests an additional role for netrin 1 in target recognition.