Lmx1a et Lmx1b sont des facteurs de transcription qui sont essentiels à la différenciation et à la spécification des neurones mDA, et contrôle plusieurs aspects de la formation des circuits dopaminergiques du mésencéphale et de leur maintien chez l’adulte. Nous avons identifié un rôle de Lmx1a et Lmx1b dans la régulation de l’excitabilité des neurones mDA de la VTA et de la SNc, par leur régulation transcriptionnelle de
Slitrk2 et Slitrk5. Tel que pour LMX1A et LMX1B, des polymorphismes des gènes Slitrk2 et Slitrk5 ont été
associés à divers désordres neuropsychiatriques comportant un aspect dysfonctionnel de la transmission dopaminergique, incluant la schizophrénie, le trouble bipolaire et les désordres des spectres autistiques et obsessif-compulsif. Alors que Slitrk2 contrôle la formation de synapses glutamatergiques afférentes aux dendrites des neurones dopaminergiques du mésencéphale, Slitrk5 y contrôle la formation de synapses GABAergiques à la densité postsynaptique.
LMX1A, LMX1B, de même que SLITRK2 et SLITRK5 constituent des pistes de recherches intéressantes
concernant la compréhension des mécanismes neurodéveloppementaux et neuropathologiques, liant divers troubles neuropsychiatriques sévères au développement des circuits dopaminergiques du mésencéphale et à la dysfonction de l’équilibre de l’activité électrophysiologique des neurones mDA. Il sera particulièrement intéressant et pertinent d’approfondir la compréhension des mécanismes cellulaires et moléculaires régulés par Lmx1a/b et Slitrk2/5, par l’étude de la perte de fonction de Slitrk2/5 in vivo, spécifiquement dans les neurones mDA de la VTA et de la SNc, afin d’observer les effets physiologiques, neurochimiques et comportementaux associés à une perturbation de la formation des synapses excitatrices et inhibitrices afférentes aux neurones mDA et à une perturbation de leur excitabilité.
Les prochaines étapes de ce projet s’attarderont au rôle des protéines Slitrk2 et Slitrk5 dans la formation des circuits dopaminergiques du mésencéphale, in vivo. L’inactivation de Slitrk2 et Slitrk5, spécifiquement dans les neurones dopaminergiques du mésencéphale, sera effectuée par injection stéréotaxique de lentivirus codant pour un shRNA ciblant l’ARNm de Slitrk2 et Slitrk5, permettant ainsi la diminution de leur expression par interférence à l’ARN, in vivo. Seront par la suite effectué une batterie de tests comportementaux, permettant d’évaluer un possible phénotype d’hyperactivité, d’anxiété et de stéréotypie, suite à l’inactivation de Slitrk2/5 et pouvant être associés à un modèle murin de maladies neuropsychiatriques humaines. Afin de supporter les analyses comportementales, des analyses morphologiques et électrophysiologiques des neurones dopaminergiques de la substantia nigra pars compacta et de l’aire tegmentale ventrale seront effectuée afin
d’évaluer l’excitabilité des neurones mDA in vivo, suite à la diminution de l’expression de Slitrk2/5. Des analyses électrochimiques et neurochimiques seront également effectuées afin de mesurer une possible variation de la libération de dopamine et de sa métabolisation au niveau des cibles corticales, striatales et limbiques des neurones mDA. De plus, l’étude des polymorphismes de LMX1A/B et SLITRK2/5 et de leur effet sur la fonction de ces protéines permettra possiblement le développement de modèles animaux permettant l’étude de maladies neuropsychiatriques humaines complexes.
Dans l’ensemble, ce projet emportera une meilleure compréhension des mécanismes cellulaires et moléculaires régulant la formation des circuits dopaminergiques du mésencéphale, des processus régulant leur activité, de même que des mécanismes pathologiques associés à une perturbation de leur fonction et pouvant mener au développement de troubles neuropsychiatriques humains.
Bibliographie
Abelson, J. F., Kwan, K. Y., O'Roak, B. J., Baek, D. Y., Stillman, A. A., Morgan, T. M., . . . State, M. W. (2005). Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science, 310(5746), 317- 320. doi:10.1126/science.1116502
Acampora, D., Avantaggiato, V., Tuorto, F., & Simeone, A. (1997). Genetic control of brain morphogenesis through Otx dosage requirement. Development, 124(18), 3639-3650.
Adams, K. A., Maida, J. M., Golden, J. A., & Riddle, R. D. (2000). The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer. Development, 127(9), 1857-1867.
Agid, Y. (1991). Parkinson's disease: pathophysiology. Lancet, 337(8753), 1321-1324.
Albéri, L., Sgadò, P., & Simon, H. H. (2004). Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons. Development, 131(13), 3229-3236. doi:10.1242/dev.01128
Almqvist, P. M., Akesson, E., Wahlberg, L. U., Pschera, H., Seiger, A., & Sundstrom, E. (1996). First trimester development of the human nigrostriatal dopamine system. Exp Neurol, 139(2), 227-237.
Anand, A., Barkay, G., Dzemidzic, M., Albrecht, D., Karne, H., Zheng, Q. H., . . . Yoder, K. K. (2011). Striatal dopamine transporter availability in unmedicated bipolar disorder. Bipolar Disord, 13(4), 406-413. doi:10.1111/j.1399-5618.2011.00936.x
Anderegg, A., Lin, H. P., Chen, J. A., Caronia-Brown, G., Cherepanova, N., Yun, B., . . . Awatramani, R. (2013). An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool. PLoS Genet, 9(12), e1003973.
doi:10.1371/journal.pgen.1003973
Andersen, P. H., Gingrich, J. A., Bates, M. D., Dearry, A., Falardeau, P., Senogles, S. E., & Caron, M. G. (1990). Dopamine receptors subtypes: beyond the D1/D2 classification. Trends Pharmacol Sci, 11, 231-236.
Andersson, E., Jensen, J. B., Parmar, M., Guillemot, F., & Björklund, A. (2006). Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2.
Development, 133(3), 507-516.
Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., . . . Ericson, J. (2006). Identification of intrinsic determinants of midbrain dopamine neurons. Cell, 124(2), 393-405. doi:10.1016/j.cell.2005.10.037
Andersson, E. R., Prakash, N., Cajanek, L., Minina, E., Bryja, V., Bryjova, L., . . . Arenas, E. (2008). Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo.
PLoS One, 3(10), e3517. doi:10.1371/journal.pone.0003517
Andersson, E. R., Salto, C., Villaescusa, J. C., Cajanek, L., Yang, S., Bryjova, L., . . . Arenas, E. (2013). Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.
Proc Natl Acad Sci U S A, 110(7), E602-610. doi:10.1073/pnas.1208524110
Andrade, L., Caraveo-Anduaga, J. J., Berglund, P., Bijl, R. V., De Graaf, R., Vollebergh, W., . . . Wittchen, H. U. (2003). The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res, 12(1), 3-21.
Ang, S. L., & Rossant, J. (1994). HNF-3 beta is essential for node and notochord formation in mouse development. Cell, 78(4), 561-574.
Ang, S. L., Wierda, A., Wong, D., Stevens, K. A., Cascio, S., Rossant, J., & Zaret, K. S. (1993). The formation and maintenance of the definitive endoderm lineage in the mouse: involvment of HNF3/forkhead proteins. Development, 119(4), 1301-1315.
Angelakis, I., Gooding, P., Tarrier, N., & Panagioti, M. (2015). Suicidality in obsessive compulsive disorder (OCD): a systematic review and meta-analysis. Clin Psychol Rev, 39, 1-15.
Arenas, E., Denham, M., & Villaescusa, J. C. (2015). How to make a midbrain dopaminergic neuron.
Development, 142(11), 1918-1936.
Aruga, J. (2003). Slitrk6 expression profile in the mouse embryo and its relationship to that of Nlrr3. Gene
Expression Patterns, 3(6), 727-733. doi:10.1016/s1567-133x(03)00141-8
Aruga, J., & Mikoshiba, K. (2003). Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth. Molecular and Cellular Neuroscience, 24(1), 117-129. doi:10.1016/s1044-7431(03)00129-5
Aruga, J., Yokota, N., & Mikoshiba, K. (2003). Human SLITRK family genes: genomic organization and expression profiling in normal brain and brain tumor tissue. Gene, 315, 87-94. doi:10.1016/s0378- 1119(03)00715-7
Baek, J. H., Hatakeyama, J., Sakamoto, S., Ohtsuka, T., & Kageyama, R. (2006). Persistent and high levels of Hes1 expression regulate boudary formation in the developing central nervous system. Development,
13(13), 2467-2476.
Beaubien, F., & Cloutier, J. F. (2009). Differential expression of Slitrk family members in the mouse nervous system. Dev Dyn, 238(12), 3285-3296. doi:10.1002/dvdy.22160
Beaulieu, J. M., & Gainetdinov, R. R. (2011). The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev, 63(1), 182-217. doi:10.1124/pr.110.002642
Beaulieu, J. M., Sotnikova, T. D., Marion, S., Lefkowitz, R. J., Gainetdinov, R. R., & Caron, M. G. (2005). An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior.
Cell, 122(2), 261-273. doi:10.1016/j.cell.2005.05.012
Beaulieu, J. M., Sotnikova, T. D., Yao, W. D., Kockeritz, L., Woodgett, J. R., Gainetdinov, R. R., & Caron, M. G. (2004). Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci U S A, 101(14), 5099-5104.
doi:10.1073/pnas.0307921101
Berg, D., Holzmann, C., & Riess, O. (2003). 14-3-3 proteins in the nervous system. Nat Rev Neurol, 4, 752- 762.
Berger, B., Verney, C., Alvarez, C., Vigny, A., & Helle, K. B. (1985). New dopaminergic terminal fields in the motor, visual (area 18b) and retrosplenial cortex in the young and adult rat. Immunocytochemical and catecholamine histochemical analyses. Neuroscience, 15(4), 983-998.
Berger, I. (2011). Diagnosis of attention deficit hyperactivity disorder: much ado about something. Isr Med
assoc J, 13(9), 571-574.
Bergman, O., Hakansson, A., Westberg, L., Belin, A. C., Sydow, O., Olson, L., . . . Nissbrandt, H. (2009). Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease.
J Neual Transm (Vienna), 116(3), 333-338.
Bergman, O., Hakansson, A., Westberg, L., Nordenstrom, K., Carmine Belin, A., Sydow, O., . . . Nissbrandt, H. (2010). PITX3 polymorphism is associated with early onset Parkinson's disease. Neurobiol Aging,
31(1), 114-117.
Bergman, O., Westberg, L., Nilsson, L.-G., Adolfsson, R., & Eriksson, E. (2010). Preliminary evidence that polymorphims in dopamine-related transcription factios LMX1A, LMX1B and PITX3 are associated with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry, 34(6), 1094-1097.
Berk, M., Dodd, S., Kauer-Sant'anna, M., Malhi, G. S., Bourin, M., Kapczinski, F., & Norman, T. (2007). Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta
Psychiatr Scand Suppl(434), 41-49. doi:10.1111/j.1600-0447.2007.01058.x
Bezard, E., & Gross, C. E. (1998). Compensatory mechanisms in experimental and human parkinsonism: towards a dynamic approach. Prog Neurobiol, 55(2), 93-116.
Bird, A. D., Tan, K. H., Olsson, P. F., Zieba, M., Flecknoe, S. J., Liddicoat, D. R., . . . Cole, T. J. (2007). Identification of glucocorticoid-regulated genes that control cell proliferation during murine respiratory development. J Physiol, 585(Pt 1), 187-201. doi:10.1113/jphysiol.2007.136796
Bjorklund, A., & Dunnett, S. B. (2007). Dopamine neuron systems in the brain: an update. Trends Neurosci,
30(5), 194-202. doi:10.1016/j.tins.2007.03.006
Blaess, S., Bodea, G. O., Kabanova, A., Chanet, S., Mugniery, E., Derouiche, A., . . . Joyner, A. L. (2011). Temportal-spatial changes in Sonic Hedgehog expression and signaling reveal different potentieals of ventral mesencephalic progenitors to populate distinct ventral midbrain nuclei. Neural Dev, 6(29). Blaess, S., Corrales, J. D., & Joyner, A. L. (2006). Sonic hedgehog regulates Gli activator and repressor
functions with spatial and temporal precision in the mid/hindbrain region. Development, 133(9), 1799- 1809. doi:10.1242/dev.02339
Blascko, H. (1939). The specific action of L-dopa decarboxylase. J Physiol (Lond), 96(50), 50-51.
Bodea, G. O., Spille, J. H., Abe, P., Andersson, A. S., Acker-Palmer, A., Stumm, R., . . . Blaess, S. (2014). Reelin and CXCL12 regulate distinct migratory behaviours during the development of the dopaminergic system. Development, 141(3), 661-673.
Bokor, G., & Anderson, P. D. (2014). Obsessive-compulsive disorder. J Pharm Pract, 27(2), 116-130. doi:10.1177/0897190014521996
Bolam, J. P., & Smith, Y. (1990). The GABA and substance P input to dopaminergic neurones in the substancia nigra of rat. Brain Res, 529(1-2), 57-78.
Bonilla, S., Hall, A. C., Pinto, L., Attardo, A., Götz, M., Huttner, W. B., & Arenas, E. (2008). Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors. Glia, 56(8), 809-820. Bookout, A. L., Cummins, C. L., Mangelsdorf, D. J., Pesola, J. M., & Kramer, M. F. (2001). High-Throughput
Real-Time Quantitative Reverse Transcription PCR Current Protocols in Molecular Biology: John Wiley & Sons, Inc.
Briscoe, J., & Ericson, J. (1999). The specification of neuronal identity by graded Sonic Hedgehog signalling.
Semin Cell Dev Biol, 10(3), 353-362.
Broccoli, V., Boncinelli, E., & Wurst, W. (1999). The caudal limit of Otx2 expression positions the isthmic organizer. Nature, 401(6749), 164-168. doi:10.1038/43670
Brodski, C., Weisenhorn, D. M., Signore, M., Sillaber, I., Oesterheld, M., Broccoli, V., . . . Wurst, W. (2003). Location and size of dopaminergic and serotonergic cell populations are controlled by the position of the midbrain-hindbrain organizer. J Neurosci, 23(10), 4199-4207.
Bromek, E., Haduch, A., Golembiowska, K., & Daniel, W. A. (2011). Cytochrome P450 mediates dopamine formation in the brain in vivo. J Neurochem, 118(5), 806-815. doi:10.1111/j.1471-4159.2011.07339.x Brose, K., & Tessier-Lavigne, M. (2000). Slit proteins: key regulators of axon guidance, axonal branching, and
cell migration. Curr Opin Neurobiol, 10(1), 95-102.
Brown, A., Machan, J. T., Hayes, L., & Zervas, M. (2011). Molecular organization and timing of Wnt1
expression define cohorts of midbrain dopamine neuron progenitors in vivo. J Comp Neurol, 519(15), 2978-3000. doi:10.1002/cne.22710
Buse, J., Schoenefeld, K., Munchau, A., & Roessner, V. (2013). Neuromodulation in Tourette syndrome: dopamine and beyond. Neurosci Biobehav Rev, 37(6), 1069-1084.
doi:10.1016/j.neubiorev.2012.10.004
Canty, A. J., & Murphy, M. (2008). Molecular mechanisms of axon guidance in the developing corticospinal tract. Prog Neurobiol, 85(2), 214-235. doi:10.1016/j.pneurobio.2008.02.001
Carlsson, A. (1988). The current status of the dopamine hypothesis of schizophrenia.
Neuropsychopharmacology, 1(3), 179-186.
Carlsson, A. (2001a). A half-century of neurotransmitter research: impact on neurology and psychiatry. Nobel lecture. Biosci Rep, 21(6), 691-710.
Carlsson, A. (2001b). A paradigm shift in brain research. Science, 294(5544), 1021-1024. doi:10.1126/science.1066969
Carlsson, A., Lindqvist, M., & Magnusson, T. (1957). 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature, 180(4596), 1200.
Carlsson, A., Lindqvist, M., Magnusson, T., & Waldbeck, B. (1958). On the presence of 3-hydroxytyramine in brain. Science, 127(3296), 471.
Carter, A. S., O'Donnell, D. A., Schultz, R. T., Scahill, L., Leckman, J. F., & Pauls, D. L. (2000). Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome: associations with
ADHD and family functionin. Attention Deficit Hyperactivity Disorder. J Child Psychol Psychiatry,
41(2), 215-223.
Castelo-Branco, G., Wagner, J., Rodriguez, F. J., Kele, J., Sousa, K., Rawal, N., . . . Arenas, E. (2003). Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a.
Proc Natl Acad Sci U S A, 100(22), 12747-12752. doi:10.1073/pnas.1534900100
Castillo, S. O., Baffi, J. S., Palkovits, M., Goldstein, D. S., Kopin, I. J., Witta, J., . . . Nikodem, V. M. (1998). Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamix neurons in mice with targeted disruption of the Nurr1 gene. Mol Cell Neurosci, 11(1-2), 36-46.
Cavani, S., Prontera, P., Grasso, M., Ardisia, C., Malacarne, M., Gradassi, C., . . . Pierluigi, M. (2011). FMR1, FMR2, and SLITRK2 deletion inside a paracentric inversion involving bands Xq27.3-q28 in a male and his mother. Am J Med Genet A, 155A(1), 221-224. doi:10.1002/ajmg.a.33515
Cazorla, P., Smidt, M. P., O'Malley, K. L., & Burbach, J. P. (2000). A response element for the homeodomain transcription factor Ptx3 in the tyrosine hydroxylase gene promoter. J Neurochem, 74(5), 1829-1837. Chakrabarty, K., Von Oerthel, L., Hellemons, A., Clotman, F., Espana, A., Groot Koerkamp, M., . . . Smidt, M.
P. (2012). Genome wide expression profiling of the mesodiencephalic region identifies novel factors involved in early and late dopaminergic development. Biol Open, 1(8), 693-704.
doi:10.1242/bio.20121230
Chao, J., & Nestler, E. J. (2004). Molecular neurobiology of drug addiction. Annu Rev Med, 55, 113-132. doi:10.1146/annurev.med.55.091902.103730
Chaudhry, F. A., Edwards, R. H., & Fonnum, F. (2008). Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances. Annu Rev Pharmacol Toxicol, 48, 277-301.
Chiang, C., Litingtung, Y., Lee, E., Young, K. E., Corden, J. L., Westphal, H., & Beachy, P. A. (1996). Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature, 383(6599), 407- 413. doi:10.1038/383407a0
Chou, I. C., Wan, L., Liu, S. C., Tsai, C. H., & Tsai, F. J. (2007). Association of the Slit and Trk-like 1 Gene in Taiwanese Patients with Tourette Syndrom. Pediatric Neurology, 37(6), 404-406.
Chung, S., Leung, A., Han, B. S., Chang, M. Y., Moon, J. I., Kim, C. H., . . . Kim, K. S. (2009). Wnt1-Lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differenciation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell, 5(6), 646-658.
Cisbani, G., Drouin-Ouellet, J., Gibrat, C., Saint-Pierre, M., Lagace, M., Badrinarayanan, S., . . . Cicchetti, F. (2015). Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease. Neurobiol Dis, 82, 430-444.
doi:10.1016/j.nbd.2015.07.012
Cooper, J. A., Esch, F. S., Taylor, S. S., & Hunter, T. (1984). Phosphorylation sites in enolase and lactate dehydrogenase utilized by tyrosine protein kinases in vivo and in vitro. J Biol Chem, 259(12), 7835- 7841.
Cortese, S. (2012). The neurobiology and genetics of attention-deficit/hyperactivity disorder (ADHD): what every clinican should know. . Eur J Paediatr Neurol, 16, 422-433.
Craddock, N., & Forty, L. (2006). Genetics of affective (mood) disorders. Eur J Hum Genet, 14(6), 660-668. doi:10.1038/sj.ejhg.5201549
Cross, D. A., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995). Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature, 378(6559), 785-789. doi:10.1038/378785a0
Dahlstroem, A., & Fuxe, K. (1964). Evidence for the Existence of Monoamine-Containing Neurons in the Central Nervous System. I. Demonstration of Monoamines in the Cell Bodies of Brain Stem Neurons.
Acta Physiol Scand Suppl, SUPPL 232:231-255.
Danielian, P. S., & McMahon, A. P. (1996). Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development. Nature, 383(6598), 332-334.
Dauer, W., & Przedborski, S. (2003). Parkinson's Disease. Neuron, 39(6), 889-909. doi:10.1016/S0896- 6273(03)00568-3
Dauer, W., & Przedborski, S. (2003). Parkinson's disease: mechanisms and models. Neuron, 39(6), 889-909. Davis, C. A., & Joyner, A. L. (1988). Expression patterns of the homeo box-containing genes En-1 and En-2
and the proto-oncogene int-1 diverge during mouse development. Genes Dev, 2(12B), 1736-1744. de Bartolomeis, A., Buonaguro, E. F., Iasevoli, F., & Tomasetti, C. (2014). The emerging role of dopamine-
glutamate interaction and of the postsynaptic density in bipolar disorder pathophysiology: Implications for treatment. J Psychopharmacol, 28(6), 505-526. doi:10.1177/0269881114523864
de Wit, J., & Ghosh, A. (2014). Control of neural circuit formation by leucine-rich repeat proteins. Trends
Neurosci, 37(10), 539-550. doi:10.1016/j.tins.2014.07.004
Dean, C., & Dresbach, T. (2006). Neuroligins and neurexins: linking cell adhesion, synapse formation and cognitive function. Trends Neurosci, 29(1), 21-29. doi:10.1016/j.tins.2005.11.003
Demyanenko, G. P., Shibata, Y., & Maness, P. F. (2001). Altered distribution of dopaminergic neurons in the brain of L1 null mice. Brain Res Dev Brain Res, 126(1), 21-30.
Deng, Andersson, E., Hedlund, E., Alekseenko, Z., Coppola, E., Panman, L., . . . Perlmann, T. (2011). Specific and integrated roles of Lmx1a, Lmx1b and Phox2a in ventral midbrain development. Development,
138(16), 3399-3408.
Deng, H., Le, W. D., Xie, W. J., & Jankovic, J. (2006). Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome. Acta Neurol Scand, 114(6), 400-402. doi:10.1111/j.1600-0404.2006.00706.x Deng, Q., Andersson, E., Hedlund, E., Alekseenko, Z., Coppola, E., Panman, L., . . . Perlmann, T. (2011).
Specific and integrated roles of Lmx1a, Lmx1b and Phox2a in ventral midbrain development.
Development, 138(16), 3399-3408. doi:10.1242/dev.065482
Deurveilher, S., & Semba, K. (2008). Reciprocal connections between the suprachiasmatic nucleus and the midbrain raphe nuclei: A putative role in the circadian control of behavioral states. In J. M. Monti (Ed.), Serotonin and Sleep: Molecular, Functional and Clinical Aspects.: Birkhäuser Basel.
Di Chiara, G. (2002). Nucleus accumbens shell and core dopamine: differential role in behavior and addiction.
Behav Brain Res, 137(1-2), 75-114.
Di Salvio, M., Di Giovannantonio, L. G., Acampora, D., Prosperi, R., Omodei, D., Prakash, N., . . . Simeone, A. (2010). Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP. Nat Neurosci, 13(12), 1481-1488. doi:10.1038/nn.2661
Di Salvio, M., Di Giovannantonio, L. G., Omodei, D., Acampora, D., & Simeone, A. (2010). Otx2 expression is restricted to dopaminergic neurons of the ventral tegmental area in the adult brain. Int J Dev Biol,
54(5), 939.
Doucet-Beaupré, H., Ang, S. L., & Lévesque, M. (2015). Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b. FEBS Lett.
Doucet-Beaupré, H., Gilbert, C., Rioux, V., Schaan Profes, M., Charest, J., Giguere, N., . . . Levesque, M. (In Revision). Transcription factors Lmx1a and Lmx1b actively maintain mitochondrial functions of midbrain dopaminergic neuron throughout lifespan. PNAS.
Doucet-Beaupré, H. L., M. (2013). The role of developmental transcription factors in adult midbrain dopaminergic neurons. OA Neurosciences.
Dray, A., Davies, J., Oakley, N. R., Tongroach, P., & Vellucci, S. (1978). The dorsal and medial raphe projections to the substancia nigra in the rat: electrophysiological, biochemical and behavioural observations. Brain Res, 151(3), 431-442.
Drevets, W. C., Gautier, C., Price, J. C., Kupfer, D. J., Kinahan, P. E., Grace, A. A., . . . Mathis, C. A. (2001). Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol
Psychiatry, 49(2), 81-96.
Duke, D. C., Keeley, M. L., Geffken, G. R., & Storch, E. A. (2010). Trichotillomania: A current review. Clin
Psychol Rev, 30(2), 181-193. doi:10.1016/j.cpr.2009.10.008
Dunah, A. W., Hueske, E., Wyszynski, M., Hoogenraad, C. C., Jaworski, J., Pak, D. T., . . . Sheng, M. (2005). LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat Neurosci, 8(4), 458-467. doi:10.1038/nn1416
Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., . . . McIntosh, I. (2004). The human LMX1B gene: transcription unit, promoter, and pathogenic mutations. Genomics, 84(3), 565- 576. doi:10.1016/j.ygeno.2004.06.002
Echelard, Y., Epstein, D. J., St-Jacques, B., Shen, L., Mohler, J., McMahon, J. A., & McMahon, A. P. (1993). Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell, 75(7), 1417-1430.
Eisenhofer, G., Kopin, I. J., & Goldstein, D. S. (2004). Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev, 56(3), 331-349. doi:10.1124/pr.56.3.1 Elbaz, A., & Tranchant, C. (2007). Epidemiologic studies of environmental exposures in Parkinson's disease. J
Neurol Sci, 262(1-2), 37-44. doi:10.1016/j.jns.2007.06.024
Embi, N., Rylatt, D. B., & Cohen, P. (1980). Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cylic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem,
107(2), 519-527.
Ericson, J., Morton, S., Kawakami, A., Roelink, H., & Jessell, T. M. (1996). Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell, 87(4), 661-673. Eriksen, J., Jorgensen, T. N., & Gether, U. (2010). Regulation of dopamine transporter function by protein-
protein interaction: new discoveries and methodological challenges. J Neurochem, 113, 27-41. Ernst, M., Zametkin, A. J., Jons, P. H., Matochik, J. A., Pascualvaca, D., & Cohen, R. M. (1999). High
presynaptic dopaminergic activity in children with Tourette's disorder. J Am Acad Child Adolesc
Psychiatry, 38(1), 86-94. doi:10.1097/00004583-199901000-00024
Everitt, B. J., & Robbins, T. W. (2013). From the ventral to the dorsal striatum: devolving views of their roles in drug addiction. Neurosci Biobehav Rev, 37, 1946-1954.
Fabbrini, G., Pasquini, M., Aurilia, C., Berardelli, I., Breedveld, G., Oostra, B. A., . . . Berardelli, A. (2007). A large Italian family with Gilles de la Tourette syndrome: clinical study and analysis of the SLITRK1 gene. Mov Disord, 22(15), 2229-2234. doi:10.1002/mds.21697
Fagiolini, A., Forgione, R., Maccari, M., Cuomo, A., Morana, B., Dell'Osso, M. C., . . . Rossi, A. (2013). Prevalence, chronicity, burden and borders of bipolar disorder. J Affect Disord, 148(2-3), 161-169. doi:10.1016/j.jad.2013.02.001
Fahn, S., & Sulzer, D. (2004). Neurodegeneration and neuroprotection in Parkison disease. NeuroRx, 1(1), 139-154.
Failli, V., Bachy, I., & Rétaux, S. (2002). Expression of the LIM-homeodomain gene Lmx1a (dreher) during development of the mouse nervous system. Mech Dev, 118(1-2), 225-228.
Fallon, J. H., & Moore, R. Y. (1978). Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J Comp Neurol, 180(3), 545-580. doi:10.1002/cne.901800310
Ferri, A. L., Lin, W., Mavromatakis, Y. E., Wang, J. C., Sasaki, H., Whitsett, J. A., & Ang, S. L. (2007). Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage- dependent manner. Development, 134(15), 2761-2769. doi:10.1242/dev.000141
Filippi, A., Durr, K., Ryu, S., Willaredt, M., Holzschuh, J., & Driever, W. (2007). Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and noradrenergic neuronal development. BMC
Dev Biol, 7(135), 135. doi:10.1186/1471-213X-7-135
Flores, C., Manitt, C., Rodaros, D., Thompson, K. M., Rajabi, H., Luk, K. C., . . . Kennedy, T. E. (2005). Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine. Mol Psychiatry, 10(6), 606-612.
Frame, S., & Cohen, P. (2001). GSK3 takes centre stage more than 20 years after its discovery. Biochem J,
359(Pt 1), 1-16.
Frank, M. J., Samanta, J., Moustafa, A. A., & Sherman, S. J. (2007). Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism. Science, 318(5854), 1309-1312.
Freeman, T. B., Spence, M. S., Boss, B. D., Spector, D. H., Strecker, R. E., Olanow, C. W., & Kordower, J. H. (1991). Development of dopaminergic neurons in the human substancia nigra. Exp Neurol, 113(3), 344-353.
Friedman, A., Friedman, Y., Dremencov, E., & Yadid, G. (2008). VTA dopamine neuron bursting is altered in an animal model of depression and corrected by desipramine. J Mol Neurosci, 34, 201-209.
Fuchs, J., Mueller, J. C., Lichtner, P., Schulte, C., Munz, M., Berg, D., . . . Gasser, T. (2009). The transcription factor PITX3 is associated with sporadic Parkinson's disease. Neurobiol Aging, 30(5), 731-738. Fusar-Poli, P., Rubia, K., Rossi, G., Sartori, G., & Balottin, U. (2012). Striatal dopamine transporter alterations
in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis. Am J Psychiatry,
169(3), 264-272. doi:10.1176/appi.ajp.2011.11060940
Gates, M. A., Coupe, V. M., Torres, E. M., Fricker-Gates, R. A., & Dunnett, S. B. (2004). Spatially and temporally restricted chemoattractive and chemorepulsive cues direct the formation of the nigro- striatal circuit. Eur J Neurosci, 19(4), 831-844.
Gerfen, C. R., Herkenham, M., & Thibault, J. (1987). The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci, 7(12), 3915-3934.
German, M. S., Wang, J., Fernald, A. A., Espinosa, R., 3rd, Le Beau, M. M., & Bell, G. I. (1994). Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13. Genomics, 24(2), 403-404. doi:10.1006/geno.1994.1639
Gingrich, J. A., & Caron, M. G. (1993). Recent advances in the molecular biology of dopamine receptors. Annu
Rev Neurosci, 16, 299-321.
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009). Candidate gene studies of ADHD: a meta-analytic review. Hum