title: Peri-pubertal emergence of UNC-5 homologue expression by dopamine neurons in rodents.
abstract: Puberty is a critical period in mesocorticolimbic dopamine (DA) system development, particularly for the medial prefrontal cortex (mPFC) projection which achieves maturity in early adulthood. The guidance cue netrin-1 organizes neuronal networks by attracting or repelling cellular processes through DCC (deleted in colorectal cancer) and UNC-5 homologue (UNC5H) receptors, respectively. We have shown that variations in netrin-1 receptor levels lead to selective reorganization of mPFC DA circuitry, and changes in DA-related behaviors, in transgenic mice and in rats. Significantly, these effects are only observed after puberty, suggesting that netrin-1 mediated effects on DA systems vary across development. Here we report on the normal expression of DCC and UNC5H in the ventral tegmental area (VTA) by DA neurons from embryonic life to adulthood, in both mice and rats. We show a dramatic and enduring pubertal change in the ratio of DCC:UNC5H receptors, reflecting a shift toward predominant UNC5H function. This shift in DCC:UNC5H ratio coincides with the pubertal emergence of UNC5H expression by VTA DA neurons. Although the distribution of DCC and UNC5H by VTA DA neurons changes during puberty, the pattern of netrin-1 immunoreactivity in these cells does not. Together, our findings suggest that DCC:UNC5H ratios in DA neurons at critical periods may have important consequences for the organization and function of mesocorticolimbic DA systems.
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
authors.forename: Colleen
authors.initials: C
authors.lastname: Manitt
authors.forename: Cassandre
authors.initials: C
authors.lastname: Labelle-Dumais
authors.forename: Conrad
authors.initials: C
authors.lastname: Eng
authors.forename: Alanna
authors.initials: A
authors.lastname: Grant
authors.forename: Andrea
authors.initials: A
authors.lastname: Mimee
authors.forename: Thomas
authors.initials: T
authors.lastname: Stroh
authors.forename: Cecilia
authors.initials: C
authors.lastname: Flores
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000075389:DCC Receptor; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075386:Netrin Receptors; D000075388:Netrin-1; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; C501912:Dcc protein, rat; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C494222:UNC-5 protein, rat; C487622:Unc5h3 protein, rat; D000075388:Netrin-1; D004298:Dopamine