title: Semaphorin 3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum.
abstract: The proper formation of synaptic connectivity in the mammalian brain is critical for complex behavior. In the striatum, balanced excitatory synaptic transmission from multiple sources onto two classes of principal neurons is required for coordinated and voluntary motor control. Here we show that the interaction between the secreted semaphorin 3E (Sema3E) and its receptor Plexin-D1 is a critical determinant of synaptic specificity in cortico-thalamo-striatal circuits in mice. We find that Sema3e (encoding Sema3E) is highly expressed in thalamostriatal projection neurons, whereas in the striatum Plxnd1 (encoding Plexin-D1) is selectively expressed in direct-pathway medium spiny neurons (MSNs). Despite physical intermingling of the MSNs, genetic ablation of Plxnd1 or Sema3e results in functional and anatomical rearrangement of thalamostriatal synapses specifically in direct-pathway MSNs without effects on corticostriatal synapses. Thus, our results demonstrate that Sema3E and Plexin-D1 specify the degree of glutamatergic connectivity between a specific source and target in the complex circuitry of the basal ganglia.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jun B
authors.initials: JB
authors.lastname: Ding
authors.forename: Won-Jong
authors.initials: WJ
authors.lastname: Oh
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
authors.forename: Chenghua
authors.initials: C
authors.lastname: Gu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D001921:Brain / Q000166:cytology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000378:metabolism*; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000166:cytology*; D003598:Cytoskeletal Proteins; D000229:Dependovirus / Q000235:genetics; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006023:Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics; D039961:Semaphorins; D015398:Signal Transduction / Q000235:genetics; D018709:Statistics, Nonparametric; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D000075402:Channelrhodopsins; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D039961:Semaphorins; D050599:Vesicular Glutamate Transport Protein 2; C473552:Plxnd1 protein, mouse; C111150:Sema3e protein, mouse; C493477:Slc17a6 protein, mouse; C098593:dopamine D1A receptor