Subdomain-mediated axon-axon signaling and chemoattraction cooperate to regulate afferent innervation of the lateral habenula

Ewoud Roberto Eduard Schmidt, Sara Brignani, Youri Adolfs, Suzanne Lemstra, Jeroen Demmers, Marina Vidaki, Amber Lee Skye Donahoo, Kersti Lilleväli, Eero Vasar, Linda Jane Richards, Domna Karagogeos, Sharon Margriet Kolk, Ronald Jeroen Pasterkamp

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

A dominant feature of neural circuitry is the organization of neuronal projections and synapses into specific brain nuclei or laminae. Lamina-specific connectivity is controlled by the selective expression of extracellular guidance and adhesion molecules in the target field. However, how (sub)nucleus-specific connections are established and whether axon-derived cues contribute to subdomain targeting are largely unknown. Here, we demonstrate that the lateral subnucleus of the habenula (lHb) determines its own afferent innervation by sending out efferent projections that express the cell adhesion molecule LAMP to reciprocally collect and guide dopaminergic afferents to the lHb-a phenomenon we term subdomain-mediated axon-axon signaling. This process of reciprocal axon-axon interactions cooperates with lHb-specific chemoattraction mediated by Netrin-1, which controls axon target entry, to ensure specific innervation of the lHb. We propose that cooperation between pretarget reciprocal axon-axon signaling and subdomain-restricted instructive cues provides a highly precise and general mechanism to establish subdomain-specific neural circuitry.

Original languageEnglish
Pages (from-to)372-387
Number of pages16
JournalNeuron
Volume83
Issue number2
DOIs
StatePublished - Jul 16 2014

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