title: The glycoprotein Ten-m3 mediates topography and patterning of thalamostriatal projections from the parafascicular nucleus in mice.
abstract: The striatum is the key input nucleus of the basal ganglia, and is implicated in motor control and learning. Despite the importance of striatal circuits, the mechanisms associated with their development are not well established. Previously, Ten-m3, a member of the Ten-m/teneurin/odz family of transmembrane glycoproteins, was found to be important in the mapping of binocular visual pathways. Here, we investigated a potential role for Ten-m3 in striatal circuit formation. In situ hybridisation revealed a patchy distribution of Ten-m3 mRNA expression superimposed on a high-dorsal to low-ventral gradient in a subregion of the striatal matrix. A survey of afferent/efferent structures associated with the matrix identified the parafascicular thalamic nucleus (PF) as a potential locus of action. Ten-m3 was also found to be expressed in a high-dorsal to low-ventral gradient in the PF, corresponding topographically to its expression in the striatum. Further, a subset of thalamic terminal clusters overlapped with Ten-m3-positive domains within the striatal matrix. Studies in wild-type (WT) and Ten-m3 knockout (KO) mice revealed no differences in overall striatal or PF structure. Thalamostriatal terminals in KOs, however, while still confined to the matrix subregion, lost their clustered appearance. Topography was also altered, with terminals from the lateral PF projecting ectopically to ventral and medial striatum, rather than remaining confined dorsolaterally as in WTs. Behaviorally, Ten-m3 KOs displayed delayed motor skill acquisition. This study demonstrates that Ten-m3 plays a key role in directing the formation of thalamostriatal circuitry, the first molecular candidate reported to regulate connectivity within this pathway.
authors.affiliation: Discipline of Physiology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Tran
authors.forename: Atomu
authors.initials: A
authors.lastname: Sawatari
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Leamey
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism*; D017403:In Situ Hybridization; D020646:Intralaminar Thalamic Nuclei / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism*; D007858:Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D012333:RNA, Messenger / Q000378:metabolism; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C525233:Tenm3 protein, mouse; D014446:Tyrosine 3-Monooxygenase
keywords: Ten-m/teneurin/odz; axon guidance; basal ganglia; striatum; thalamus