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The Journal of Neuroscience, November 1, 2002, 22(21):9352-9357

Miswiring of Limbic Thalamocortical Projections in the Absence of Ephrin-A5

Daniela Uziel^{1, 2}, Sven Mühlfriedel¹, Kostas Zarbalis³, Wolfgang Wurst³, Pat Levitt⁴, and Jürgen Bolz¹

¹ Universität Jena, Institut für Allgemeine Zoologie und Tierphysiologie, 07743 Jena, Germany, ² Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21949-590 Rio de Janeiro, Brazil, ³ Max-Planck-Institut für Psychiatrie, 80804 Munich, Germany, and ⁴ Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Axon guidance cues of the ephrin ligand family have been hypothesized to regulate the formation of thalamocortical connections, but in vivo evidence for such a role has not been examined directly. To test whether ephrin-mediated repulsive cues participate in sorting the projections originating from distinct thalamic nuclei, we analyzed the organization of somatosensory and anterior cingulate afferents postnatally in mice lacking ephrin-A5 gene expression. Projections from ventrobasal and laterodorsal nuclei to their respective sensory and limbic cortical areas developed normally. However, a portion of limbic thalamic neurons from the laterodorsal nucleus also formed additional projections to somatosensory cortical territories, thus maintaining inappropriate dual projections to multiple cortical regions. These results suggest that ephrin-A5 is not required for the formation of normal cortical projections from the appropriate thalamic nuclei, but rather acts as a guidance cue that restricts limbic thalamic axons from inappropriate neocortical regions.

Key words: wiring molecules; axonal guidance; cortical development; limbic system; thalamocortical circuits; ephrin

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22219352-06$05.00/0

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