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1863-266122152016JunBrain structure & functionBrain Struct FunctMolecular anatomy of the thalamic complex and the underlying transcription factors.249325102493-51010.1007/s00429-015-1052-5Thalamocortical loops have been implicated in the control of higher-order cognitive functions, but advances in our understanding of the molecular underpinnings of neocortical organization have not been accompanied by similar analyses in the thalamus. Using expression-based correlation maps and the manual mapping of mouse and human datasets available in the Allen Brain Atlas, we identified a few individual regions and several sets of molecularly related nuclei that partially overlap with the classic grouping that is based on topographical localization and thalamocortical connections. These new molecular divisions of the adult thalamic complex are defined by the combinatorial expression of Tcf7l2, Lef1, Gbx2, Prox1, Pou4f1, Esrrg, and Six3 transcription factor genes. Further in silico and experimental analyses provided the evidence that TCF7L2 might be a pan-thalamic specifier. These results provide substantial insights into the "molecular logic" that underlies organization of the thalamic complex.NagalskiAndrzejALaboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, Warsaw, 00-927, Poland.PuellesLuisLDepartment of Human Anatomy, University of Murcia and IMIB, Murcia, 30071, Spain.DabrowskiMichalMLaboratory of Bioinformatics, Center of Neurobiology, Nencki Institute of Experimental Biology, Warsaw, 02-093, Poland.WegierskiTomaszTLaboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.KuznickiJacekJLaboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland.WisniewskaMarta BMB0000-0002-1593-0361Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, 02-109, Poland. m.wisniewska@cent.uw.edu.pl.Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, Warsaw, 00-927, Poland. m.wisniewska@cent.uw.edu.pl.engJournal ArticleResearch Support, Non-U.S. Gov't20150512
GermanyBrain Struct Funct1012820011863-26530Eye Proteins0Homeodomain Proteins0Lymphoid Enhancer-Binding Factor 10Nerve Tissue Proteins0Receptors, Estrogen0Transcription Factor 7-Like 2 Protein0Transcription Factor Brn-3A0Transcription Factors0Tumor Suppressor Proteins0Homeobox Protein SIX30Prospero-Related Homeobox 1 Protein0ESRRG protein, human0GBX2 protein, human0LEF1 protein, human0POU4F1 protein, human0TCF7L2 protein, humanIMAnimalsAtlases as TopicDatabases, ChemicalEye ProteinsgeneticsmetabolismGene ExpressionGene Expression Regulation, DevelopmentalHomeodomain ProteinsgeneticsmetabolismHumansLymphoid Enhancer-Binding Factor 1geneticsmetabolismMiceNerve Tissue ProteinsgeneticsmetabolismReceptors, EstrogengeneticsmetabolismThalamic NucleimetabolismTranscription Factor 7-Like 2 ProteingeneticsmetabolismTranscription Factor Brn-3AgeneticsmetabolismTranscription FactorsgeneticsmetabolismTumor Suppressor ProteinsgeneticsmetabolismHomeobox Protein SIX3Prospero-Related Homeobox 1 ProteinBrain anatomyGenoarchitectureTCF7L2ThalamusTranscription factors201491920154272015513602015513602017921602015512ppublish25963709PMC488420310.1007/s00429-015-1052-510.1007/s00429-015-1052-5Aggleton JP, O’Mara SM, Vann SD, Wright NF, Tsanov M, Erichsen JT. Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. Eur J Neurosci. 2010;31(12):2292–2307. doi: 10.1111/j.1460-9568.2010.07251.x.10.1111/j.1460-9568.2010.07251.xPMC293611320550571Aizawa H, Amo R, Okamoto H. Phylogeny and ontogeny of the habenular structure. Front Neurosci. 2011;5:138. doi: 10.3389/fnins.2011.00138.10.3389/fnins.2011.00138PMC324407222203792Alelú-Paz R, Giménez-Amaya JM. The mediodorsal thalamic nucleus and schizophrenia. J Psychiatry Neurosci. 2008;33(6):489–498.PMC257576318982171Alkelai A, Greenbaum L, Lupoli S, Kohn Y, Sarner-Kanyas K, Ben-Asher E, Lancet D, Macciardi F, Lerer B. Association of the type 2 diabetes mellitus susceptibility gene, TCF7L2, with schizophrenia in an Arab-Israeli family sample. PLoS ONE. 2012;7(1):e29228. doi: 10.1371/journal.pone.0029228.10.1371/journal.pone.0029228PMC325614522247771Alonso A, Merchán P, Sandoval JE, Sánchez-Arrones L, Garcia-Cazorla A, Artuch R, Ferrán JL, Martínez-de-la-Torre M, Puelles L. Development of the serotonergic cells in murine raphe nuclei and their relations with rhombomeric domains. Brain Struct Funct. 2013;218(5):1229–1277. doi: 10.1007/s00429-012-0456-8.10.1007/s00429-012-0456-8PMC374832323052546Angevine JB. Time of neuron origin in the diencephalon of the mouse. An autoradiographic study. J Comp Neurol. 1970;139(2):129–187. doi: 10.1002/cne.901390202.10.1002/cne.9013902025463599Baldwin MK, Wong P, Reed JL, Kaas JH. Superior colliculus connections with visual thalamus in gray squirrels (Sciurus carolinensis): evidence for four subdivisions within the pulvinar complex. J Comp Neurol. 2011;519(6):1071–1094. doi: 10.1002/cne.22552.10.1002/cne.22552PMC368631421344403Bassett EA, Wallace VA. Cell fate determination in the vertebrate retina. Trends Neurosci. 2012;35(9):565–573. doi: 10.1016/j.tins.2012.05.004.10.1016/j.tins.2012.05.00422704732Baumgardt M, Miguel-Aliaga I, Karlsson D, Ekman H, Thor S. Specification of neuronal identities by feedforward combinatorial coding. PLoS Biol. 2007;5(2):e37. doi: 10.1371/journal.pbio.0050037.10.1371/journal.pbio.0050037PMC179095117298176Behrendt RP. Hallucinations: synchronisation of thalamocortical gamma oscillations under constrained by sensory input. Conscious Cogn. 2003;12(3):413–451. doi: 10.1016/S1053-8100(03)00017-5.10.1016/S1053-8100(03)00017-512941286Belgard TG, Marques AC, Oliver PL, Abaan HO, Sirey TM, Hoerder-Suabedissen A, García-Moreno F, Molnár Z, Margulies EH, Ponting CP. A transcriptomic atlas of mouse neocortical layers. Neuron. 2011;71(4):605–616. doi: 10.1016/j.neuron.2011.06.039.10.1016/j.neuron.2011.06.039PMC316327221867878Beretta CA, Dross N, Bankhead P, Carl M. The ventral habenulae of zebrafish develop in prosomere 2 dependent on Tcf7l2 function. Neural Dev. 2013;8:19. doi: 10.1186/1749-8104-8-19.10.1186/1749-8104-8-19PMC382792724067090Bernard A, Lubbers LS, Tanis KQ, Luo R, Podtelezhnikov AA, Finney EM, McWhorter MM, Serikawa K, Lemon T, Morgan R, Copeland C, Smith K, Cullen V, Davis-Turak J, Lee CK, Sunkin SM, Loboda AP, Levine DM, Stone DJ, Hawrylycz MJ, Roberts CJ, Jones AR, Geschwind DH, Lein ES. Transcriptional architecture of the primate neocortex. Neuron. 2012;73(6):1083–1099. doi: 10.1016/j.neuron.2012.03.002.10.1016/j.neuron.2012.03.002PMC362874622445337Bluske KK, Kawakami Y, Koyano-Nakagawa N, Nakagawa Y. Differential activity of Wnt/beta-catenin signaling in the embryonic mouse thalamus. Dev Dyn. 2009;238(12):3297–3309. doi: 10.1002/dvdy.22167.10.1002/dvdy.22167PMC282760619924825Boj SF, van Es JH, Huch M, Li VS, José A, Hatzis P, Mokry M, Haegebarth A, van den Born M, Chambon P, Voshol P, Dor Y, Cuppen E, Fillat C, Clevers H. Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell. 2012;151(7):1595–1607. doi: 10.1016/j.cell.2012.10.053.10.1016/j.cell.2012.10.05323260145Bourassa J, Deschênes M. Corticothalamic projections from the primary visual cortex in rats: a single fiber study using biocytin as an anterograde tracer. Neuroscience. 1995;66(2):253–263. doi: 10.1016/0306-4522(95)00009-8.10.1016/0306-4522(95)00009-87477870Bruno RM, Sakmann B. Cortex is driven by weak but synchronously active thalamocortical synapses. Science. 2006;312(5780):1622–1627. doi: 10.1126/science.1124593.10.1126/science.112459316778049Byne W, Hazlett EA, Buchsbaum MS, Kemether E. The thalamus and schizophrenia: current status of research. Acta Neuropathol. 2009;117(4):347–368. doi: 10.1007/s00401-008-0404-0.10.1007/s00401-008-0404-018604544Chen L, Guo Q, Li JY. Transcription factor Gbx2 acts cell-nonautonomously to regulate the formation of lineage-restriction boundaries of the thalamus. Development. 2009;136(8):1317–1326. doi: 10.1242/dev.030510.10.1242/dev.030510PMC268746319279136Chou SJ, Babot Z, Leingärtner A, Studer M, Nakagawa Y, O’Leary DD. Geniculocortical input drives genetic distinctions between primary and higher-order visual areas. Science. 2013;340(6137):1239–1242. doi: 10.1126/science.1232806.10.1126/science.1232806PMC385141123744949Clascá F, Rubio-Garrido P, Jabaudon D. Unveiling the diversity of thalamocortical neuron subtypes. Eur J Neurosci. 2012;35(10):1524–1532. doi: 10.1111/j.1460-9568.2012.08033.x.10.1111/j.1460-9568.2012.08033.x22606998Consortium SWGotPG Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421–427. doi: 10.1038/nature13595.10.1038/nature13595PMC411237925056061Constantinople CM, Bruno RM. Deep cortical layers are activated directly by thalamus. Science. 2013;340(6140):1591–1594. doi: 10.1126/science.1236425.10.1126/science.1236425PMC420332023812718Cronenwett WJ, Csernansky J. Thalamic pathology in schizophrenia. Curr Top Behav Neurosci. 2010;4:509–528. doi: 10.1007/7854_2010_55.10.1007/7854_2010_5521312411Crunelli V, Hughes SW. The slow (<1 Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators. Nat Neurosci. 2010;13(1):9–17. doi: 10.1038/nn.2445.10.1038/nn.2445PMC298082219966841Del Barrio MG, Bourane S, Grossmann K, Schüle R, Britsch S, O’Leary DD, Goulding M. A transcription factor code defines nine sensory interneuron subtypes in the mechanosensory area of the spinal cord. PLoS ONE. 2013;8(11):e77928. doi: 10.1371/journal.pone.0077928.10.1371/journal.pone.0077928PMC381716624223744Deschênes M, Veinante P, Zhang ZW. The organization of corticothalamic projections: reciprocity versus parity. Brain Res Brain Res Rev. 1998;28(3):286–308. doi: 10.1016/S0165-0173(98)00017-4.10.1016/S0165-0173(98)00017-49858751Ehrman LA, Mu X, Waclaw RR, Yoshida Y, Vorhees CV, Klein WH, Campbell K. The LIM homeobox gene Isl1 is required for the correct development of the striatonigral pathway in the mouse. Proc Natl Acad Sci USA. 2013;110(42):E4026–E4035. doi: 10.1073/pnas.1308275110.10.1073/pnas.1308275110PMC380107224082127Ellison-Wright I, Bullmore E. Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophr Res. 2010;117(1):1–12. doi: 10.1016/j.schres.2009.12.022.10.1016/j.schres.2009.12.02220071149Flames N, Hobert O. Gene regulatory logic of dopamine neuron differentiation. Nature. 2009;458(7240):885–889. doi: 10.1038/nature07929.10.1038/nature07929PMC267156419287374Flames N, Pla R, Gelman DM, Rubenstein JL, Puelles L, Marín O. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci. 2007;27(36):9682–9695. doi: 10.1523/JNEUROSCI.2750-07.2007.10.1523/JNEUROSCI.2750-07.2007PMC491665217804629Frietze S, Wang R, Yao L, Tak YG, Ye Z, Gaddis M, Witt H, Farnham PJ, Jin VX. Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3. Genome Biol. 2012;13(9):R52. doi: 10.1186/gb-2012-13-9-r52.10.1186/gb-2012-13-9-r52PMC349139622951069Geisler S, Andres KH, Veh RW. Morphologic and cytochemical criteria for the identification and delineation of individual subnuclei within the lateral habenular complex of the rat. J Comp Neurol. 2003;458(1):78–97. doi: 10.1002/cne.10566.10.1002/cne.1056612577324Goldberg JH, Fee MS. A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds. Nat Neurosci. 2012;15(4):620–627. doi: 10.1038/nn.3047.10.1038/nn.3047PMC332136922327474González G, Puelles L, Medina L. Organization of the mouse dorsal thalamus based on topology, calretinin immunostaining, and gene expression. Brain Res Bull. 2002;57(3–4):439–442. doi: 10.1016/S0361-9230(01)00720-1.10.1016/S0361-9230(01)00720-111923006Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 2007;62(5):429–437. doi: 10.1016/j.biopsych.2006.09.020.10.1016/j.biopsych.2006.09.020PMC200124417210143Groenewegen HJ, Galis-de Graaf Y, Smeets WJ. Integration and segregation of limbic cortico-striatal loops at the thalamic level: an experimental tracing study in rats. J Chem Neuroanat. 1999;16(3):167–185. doi: 10.1016/S0891-0618(99)00009-5.10.1016/S0891-0618(99)00009-510422737Guillery RW, Feig SL, Lozsádi DA. Paying attention to the thalamic reticular nucleus. Trends Neurosci. 1998;21(1):28–32. doi: 10.1016/S0166-2236(97)01157-0.10.1016/S0166-2236(97)01157-09464683Hawrylycz M, Bernard A, Lau C, Sunkin SM, Chakravarty MM, Lein ES, Jones AR, Ng L. Areal and laminar differentiation in the mouse neocortex using large scale gene expression data. Methods. 2010;50(2):113–121. doi: 10.1016/j.ymeth.2009.09.005.10.1016/j.ymeth.2009.09.00519800006Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, Daly BD, Dang C, Datta S, Dee N, Dolbeare TA, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeira PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sunkin SM, Swanson BE, Vawter MP, Williams D, Wohnoutka P, Zielke HR, Geschwind DH, Hof PR, Smith SM, Koch C, Grant SG, Jones AR. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012;489(7416):391–399. doi: 10.1038/nature11405.10.1038/nature11405PMC424302622996553Hobert O. Regulation of terminal differentiation programs in the nervous system. Annu Rev Cell Dev Biol. 2011;27:681–696. doi: 10.1146/annurev-cellbio-092910-154226.10.1146/annurev-cellbio-092910-15422621985672Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57. doi: 10.1038/nprot.2008.211.10.1038/nprot.2008.21119131956Iossifov I, O’Roak BJ, Sanders SJ, Ronemus M, Krumm N, Levy D, Stessman HA, Witherspoon KT, Vives L, Patterson KE, Smith JD, Paeper B, Nickerson DA, Dea J, Dong S, Gonzalez LE, Mandell JD, Mane SM, Murtha MT, Sullivan CA, Walker MF, Waqar Z, Wei L, Willsey AJ, Yamrom B, Lee YH, Grabowska E, Dalkic E, Wang Z, Marks S, Andrews P, Leotta A, Kendall J, Hakker I, Rosenbaum J, Ma B, Rodgers L, Troge J, Narzisi G, Yoon S, Schatz MC, Ye K, McCombie WR, Shendure J, Eichler EE, State MW, Wigler M. The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014;515(7526):216–221. doi: 10.1038/nature13908.10.1038/nature13908PMC431387125363768Jones EG, Rubenstein JL. Expression of regulatory genes during differentiation of thalamic nuclei in mouse and monkey. J Comp Neurol. 2004;477(1):55–80. doi: 10.1002/cne.20234.10.1002/cne.2023415281080Karalay O, Doberauer K, Vadodaria KC, Knobloch M, Berti L, Miquelajauregui A, Schwark M, Jagasia R, Taketo MM, Tarabykin V, Lie DC, Jessberger S. Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis. Proc Natl Acad Sci USA. 2011;108(14):5807–5812. doi: 10.1073/pnas.1013456108.10.1073/pnas.1013456108PMC307839221436036Kratsios P, Stolfi A, Levine M, Hobert O. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene. Nat Neurosci. 2012;15(2):205–214. doi: 10.1038/nn.2989.10.1038/nn.2989PMC326787722119902Krout KE, Loewy AD, Westby GW, Redgrave P. Superior colliculus projections to midline and intralaminar thalamic nuclei of the rat. J Comp Neurol. 2001;431(2):198–216. doi: 10.1002/1096-9861(20010305)431:2<198::AID-CNE1065>3.0.CO;2-8.10.1002/1096-9861(20010305)431:2<198::AID-CNE1065>3.0.CO;2-811170000Krout KE, Belzer RE, Loewy AD. Brainstem projections to midline and intralaminar thalamic nuclei of the rat. J Comp Neurol. 2002;448(1):53–101. doi: 10.1002/cne.10236.10.1002/cne.1023612012375Kumari V, Fannon D, Ffytche DH, Raveendran V, Antonova E, Premkumar P, Cooke MA, Anilkumar AP, Williams SC, Andrew C, Johns LC, Fu CH, McGuire PK, Kuipers E. Functional MRI of verbal self-monitoring in schizophrenia: performance and illness-specific effects. Schizophr Bull. 2010;36(4):740–755. doi: 10.1093/schbul/sbn148.10.1093/schbul/sbn148PMC289458718997158Lavado A, Lagutin OV, Oliver G. Six3 inactivation causes progressive caudalization and aberrant patterning of the mammalian diencephalon. Development. 2008;135(3):441–450. doi: 10.1242/dev.010082.10.1242/dev.01008218094027Ledoux JE, Ruggiero DA, Forest R, Stornetta R, Reis DJ. Topographic organization of convergent projections to the thalamus from the inferior colliculus and spinal cord in the rat. J Comp Neurol. 1987;264(1):123–146. doi: 10.1002/cne.902640110.10.1002/cne.9026401102445791Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007;445(7124):168–176. doi: 10.1038/nature05453.10.1038/nature0545317151600Li S, Kirouac GJ. Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala. J Comp Neurol. 2008;506(2):263–287. doi: 10.1002/cne.21502.10.1002/cne.2150218022956Li S, Kirouac GJ. Sources of inputs to the anterior and posterior aspects of the paraventricular nucleus of the thalamus. Brain Struct Funct. 2012;217(2):257–273. doi: 10.1007/s00429-011-0360-7.10.1007/s00429-011-0360-722086160Li K, Zhang J, Li JY. Gbx2 plays an essential but transient role in the formation of thalamic nuclei. PLoS ONE. 2012;7(10):e47111. doi: 10.1371/journal.pone.0047111.10.1371/journal.pone.0047111PMC346424123056596Li CT, Chen LF, Tu PC, Wang SJ, Chen MH, Su TP, Hsieh JC. Impaired prefronto-thalamic functional connectivity as a key feature of treatment-resistant depression: a combined MEG, PET and rTMS study. PLoS One. 2013;8(8):e70089. doi: 10.1371/journal.pone.0070089.10.1371/journal.pone.0070089PMC373227823936378Liu C, Maejima T, Wyler SC, Casadesus G, Herlitze S, Deneris ES. Pet-1 is required across different stages of life to regulate serotonergic function. Nat Neurosci. 2010;13(10):1190–1198. doi: 10.1038/nn.2623.10.1038/nn.2623PMC294758620818386Martinez-Ferre A, Martinez S. Molecular regionalization of the diencephalon. Front Neurosci. 2012;6:73. doi: 10.3389/fnins.2012.00073.10.3389/fnins.2012.00073PMC336046122654731McAllister JP, II, Das GD. Neurogenesis in the epithalamus, dorsal thalamus and ventral thalamus of the rat: an autoradiographic and cytological study. J Comp Neurol. 1977;172(4):647–686. doi: 10.1002/cne.901720407.10.1002/cne.901720407838894McAlonan K, Cavanaugh J, Wurtz RH. Guarding the gateway to cortex with attention in visual thalamus. Nature. 2008;456(7220):391–394. doi: 10.1038/nature07382.10.1038/nature07382PMC271303318849967Mitrofanis J, Mikuletic L. Organisation of the cortical projection to the zona incerta of the thalamus. J Comp Neurol. 1999;412(1):173–185. doi: 10.1002/(SICI)1096-9861(19990913)412:1<173::AID-CNE13>3.0.CO;2-Q.10.1002/(SICI)1096-9861(19990913)412:1<173::AID-CNE13>3.0.CO;2-Q10440718Molyneaux BJ, Arlotta P, Menezes JR, Macklis JD. Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci. 2007;8(6):427–437. doi: 10.1038/nrn2151.10.1038/nrn215117514196Motulsky H. Intuitive biostatistics. Oxford: Oxford University Press; 2013.Nagalski A, Irimia M, Szewczyk L, Ferran JL, Misztal K, Kuznicki J, Wisniewska MB. Postnatal isoform switch and protein localization of LEF1 and TCF7L2 transcription factors in cortical, thalamic, and mesencephalic regions of the adult mouse brain. Brain Struct Funct. 2013;218(6):1531–1549. doi: 10.1007/s00429-012-0474-6.10.1007/s00429-012-0474-6PMC382514223152144Nair A, Treiber JM, Shukla DK, Shih P, Müller RA. Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity. Brain. 2013;136(Pt 6):1942–1955. doi: 10.1093/brain/awt079.10.1093/brain/awt079PMC367345623739917Nakagawa Y, O’Leary DD. Combinatorial expression patterns of LIM-homeodomain and other regulatory genes parcellate developing thalamus. J Neurosci. 2001;21(8):2711–2725.PMC676251811306624Nakagawa Y, O’Leary DD. Dynamic patterned expression of orphan nuclear receptor genes RORalpha and RORbeta in developing mouse forebrain. Dev Neurosci. 2003;25(2–4):234–244. doi: 10.1159/000072271.10.1159/00007227112966220Nenadic I, Maitra R, Basmanav FB, Schultz CC, Lorenz C, Schachtzabel C, Smesny S, Nöthen MM, Cichon S, Reichenbach JR, Sauer H, Schlösser RG, Gaser C. ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects. Psychol Med. 2015;45(1):143–152. doi: 10.1017/S0033291714001159.10.1017/S003329171400115925065377Ng L, Bernard A, Lau C, Overly CC, Dong HW, Kuan C, Pathak S, Sunkin SM, Dang C, Bohland JW, Bokil H, Mitra PP, Puelles L, Hohmann J, Anderson DJ, Lein ES, Jones AR, Hawrylycz M. An anatomic gene expression atlas of the adult mouse brain. Nat Neurosci. 2009;12(3):356–362. doi: 10.1038/nn.2281.10.1038/nn.228119219037O’Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L, Dwyer S, Holmans P, Marchini JL, Spencer CC, Howie B, Leung HT, Hartmann AM, Möller HJ, Morris DW, Shi Y, Feng G, Hoffmann P, Propping P, Vasilescu C, Maier W, Rietschel M, Zammit S, Schumacher J, Quinn EM, Schulze TG, Williams NM, Giegling I, Iwata N, Ikeda M, Darvasi A, Shifman S, He L, Duan J, Sanders AR, Levinson DF, Gejman PV, Cichon S, Nöthen MM, Gill M, Corvin A, Rujescu D, Kirov G, Owen MJ, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Cloninger CR, Collaboration MGoS Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet. 2008;40(9):1053–1055. doi: 10.1038/ng.201.10.1038/ng.20118677311Oh SW, Harris JA, Ng L, Winslow B, Cain N, Mihalas S, Wang Q, Lau C, Kuan L, Henry AM, Mortrud MT, Ouellette B, Nguyen TN, Sorensen SA, Slaughterbeck CR, Wakeman W, Li Y, Feng D, Ho A, Nicholas E, Hirokawa KE, Bohn P, Joines KM, Peng H, Hawrylycz MJ, Phillips JW, Hohmann JG, Wohnoutka P, Gerfen CR, Koch C, Bernard A, Dang C, Jones AR, Zeng H. A mesoscale connectome of the mouse brain. Nature. 2014;508(7495):207–214. doi: 10.1038/nature13186.10.1038/nature13186PMC510206424695228Parnaudeau S, O’Neill PK, Bolkan SS, Ward RD, Abbas AI, Roth BL, Balsam PD, Gordon JA, Kellendonk C. Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition. Neuron. 2013;77(6):1151–1162. doi: 10.1016/j.neuron.2013.01.038.10.1016/j.neuron.2013.01.038PMC362982223522049Pinault D. Dysfunctional thalamus-related networks in schizophrenia. Schizophr Bull. 2011;37(2):238–243. doi: 10.1093/schbul/sbq165.10.1093/schbul/sbq165PMC304461521307040Popken GJ, Bunney WE, Potkin SG, Jones EG. Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. Proc Natl Acad Sci USA. 2000;97(16):9276–9280. doi: 10.1073/pnas.150243397.10.1073/pnas.150243397PMC1685810908653Poulet JF, Fernandez LM, Crochet S, Petersen CC. Thalamic control of cortical states. Nat Neurosci. 2012;15(3):370–372. doi: 10.1038/nn.3035.10.1038/nn.303522267163Power BD, Kolmac CI, Mitrofanis J. Evidence for a large projection from the zona incerta to the dorsal thalamus. J Comp Neurol. 1999;404(4):554–565. doi: 10.1002/(SICI)1096-9861(19990222)404:4<554::AID-CNE10>3.0.CO;2-2.10.1002/(SICI)1096-9861(19990222)404:4<554::AID-CNE10>3.0.CO;2-29987997Pratt JA, Morris BJ. The thalamic reticular nucleus: a functional hub for thalamocortical network dysfunction in schizophrenia and a target for drug discovery. J Psychopharmacol. 2015;29(2):127–137. doi: 10.1177/0269881114565805.10.1177/026988111456580525586397Pratt T, Vitalis T, Warren N, Edgar JM, Mason JO, Price DJ. A role for Pax6 in the normal development of dorsal thalamus and its cortical connections. Development. 2000;127(23):5167–5178.11060242Puelles L, Martinez S. Patterning of the diencephalon. Comprehensive developmental neuroscience: patterning and cell type specification in the developing CNS and PNS. 1. San Diego: Academic Press; 2013.Puelles L, Rubenstein JL. Forebrain gene expression domains and the evolving prosomeric model. Trends Neurosci. 2003;26(9):469–476. doi: 10.1016/S0166-2236(03)00234-0.10.1016/S0166-2236(03)00234-012948657Puelles L, Martinez-de-la-Torre M, Watson C. Diencephalon. The mouse nervous system. San Diego: Elsevier Academic Press; 2012.Puelles L, Fernández B, Martinez-de-la-Torre M. Neuromeric landmarks in the rat midbrain, diencephalon and hypothalamus, compared with acetylcholinesterase histochemistry. The rat nervous system. 4. New York: Academic Press/Elsevier; 2015.Purushothaman G, Marion R, Li K, Casagrande VA. Gating and control of primary visual cortex by pulvinar. Nat Neurosci. 2012;15(6):905–912. doi: 10.1038/nn.3106.10.1038/nn.3106PMC343082422561455Quina LA, Wang S, Ng L, Turner EE. Brn3a and Nurr1 mediate a gene regulatory pathway for habenula development. J Neurosci. 2009;29(45):14309–14322. doi: 10.1523/JNEUROSCI.2430-09.2009.10.1523/JNEUROSCI.2430-09.2009PMC280283219906978Radenbach K, Flaig V, Schneider-Axmann T, Usher J, Reith W, Falkai P, Gruber O, Scherk H. Thalamic volumes in patients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2010;260(8):601–607. doi: 10.1007/s00406-010-0100-7.10.1007/s00406-010-0100-7PMC299586820127489Rendahl H. Embryologische und morphologische studien über das zwischenhirn beim Huhn. Acta Zoologica. 1924;5(1–2):241–344. doi: 10.1111/j.1463-6395.1924.tb00169.x.10.1111/j.1463-6395.1924.tb00169.xSaalmann YB, Kastner S. Cognitive and perceptual functions of the visual thalamus. Neuron. 2011;71(2):209–223. doi: 10.1016/j.neuron.2011.06.027.10.1016/j.neuron.2011.06.027PMC314818421791281Saalmann YB, Pinsk MA, Wang L, Li X, Kastner S. The pulvinar regulates information transmission between cortical areas based on attention demands. Science. 2012;337(6095):753–756. doi: 10.1126/science.1223082.10.1126/science.1223082PMC371409822879517Savic D, Distler MG, Sokoloff G, Shanahan NA, Dulawa SC, Palmer AA, Nobrega MA. Modulation ofTcf7l2 expression alters behavior in mice. PLoS ONE. 2011;6(10):e26897. doi: 10.1371/journal.pone.0026897.10.1371/journal.pone.0026897PMC320317022046400Scholpp S, Lumsden A. Building a bridal chamber: development of the thalamus. Trends Neurosci. 2010;33(8):373–380. doi: 10.1016/j.tins.2010.05.003.10.1016/j.tins.2010.05.003PMC295431320541814Shibata H, Naito J. Organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei in the rat. Brain Res. 2005;1059(1):93–103. doi: 10.1016/j.brainres.2005.08.025.10.1016/j.brainres.2005.08.02516157311Shimogori T, Lee DA, Miranda-Angulo A, Yang Y, Wang H, Jiang L, Yoshida AC, Kataoka A, Mashiko H, Avetisyan M, Qi L, Qian J, Blackshaw S. A genomic atlas of mouse hypothalamic development. Nat Neurosci. 2010;13(6):767–775. doi: 10.1038/nn.2545.10.1038/nn.2545PMC406776920436479Shirasaki R, Pfaff SL. Transcriptional codes and the control of neuronal identity. Annu Rev Neurosci. 2002;25:251–281. doi: 10.1146/annurev.neuro.25.112701.142916.10.1146/annurev.neuro.25.112701.14291612052910Siegert S, Cabuy E, Scherf BG, Kohler H, Panda S, Le YZ, Fehling HJ, Gaidatzis D, Stadler MB, Roska B. Transcriptional code and disease map for adult retinal cell types. Nat Neurosci. 2012;15(3):487–495. doi: 10.1038/nn.3032.10.1038/nn.303222267162Smidt MP, Burbach JP. A passport to neurotransmitter identity. Genome Biol. 2009;10(7):229. doi: 10.1186/gb-2009-10-7-229.10.1186/gb-2009-10-7-229PMC272852119591649Sommer MA. The role of the thalamus in motor control. Curr Opin Neurobiol. 2003;13(6):663–670. doi: 10.1016/j.conb.2003.10.014.10.1016/j.conb.2003.10.01414662366Sommer MA, Wurtz RH. Influence of the thalamus on spatial visual processing in frontal cortex. Nature. 2006;444(7117):374–377. doi: 10.1038/nature05279.10.1038/nature0527917093408Sun Y, Hu D, Liang J, Bao YP, Meng SQ, Lu L, Shi J. Association between variants of zinc finger genes and psychiatric disorders: systematic review and meta-analysis. Schizophr Res. 2015;162(1–3):124–137. doi: 10.1016/j.schres.2015.01.036.10.1016/j.schres.2015.01.03625667193Suzuki-Hirano A, Ogawa M, Kataoka A, Yoshida AC, Itoh D, Ueno M, Blackshaw S, Shimogori T. Dynamic spatiotemporal gene expression in embryonic mouse thalamus. J Comp Neurol. 2011;519(3):528–543. doi: 10.1002/cne.22531.10.1002/cne.2253121192082Taube JS. Head direction cells recorded in the anterior thalamic nuclei of freely moving rats. J Neurosci. 1995;15(1 Pt 1):70–86.PMC65782887823153Theyel BB, Llano DA, Sherman SM. The corticothalamocortical circuit drives higher-order cortex in the mouse. Nat Neurosci. 2010;13(1):84–88. doi: 10.1038/nn.2449.10.1038/nn.2449PMC284643819966840Thompson CL, Pathak SD, Jeromin A, Ng LL, MacPherson CR, Mortrud MT, Cusick A, Riley ZL, Sunkin SM, Bernard A, Puchalski RB, Gage FH, Jones AR, Bajic VB, Hawrylycz MJ, Lein ES. Genomic anatomy of the hippocampus. Neuron. 2008;60(6):1010–1021. doi: 10.1016/j.neuron.2008.12.008.10.1016/j.neuron.2008.12.00819109908Toresson H, Parmar M, Campbell K. Expression of Meis and Pbx genes and their protein products in the developing telencephalon: implications for regional differentiation. Mech Dev. 2000;94(1–2):183–187. doi: 10.1016/S0925-4773(00)00324-5.10.1016/S0925-4773(00)00324-510842069Van der Werf YD, Witter MP, Groenewegen HJ. The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Brain Res Rev. 2002;39(2–3):107–140. doi: 10.1016/S0165-0173(02)00181-9.10.1016/S0165-0173(02)00181-912423763Van Groen T, Wyss JM. Projections from the anterodorsal and anteroventral nucleus of the thalamus to the limbic cortex in the rat. J Comp Neurol. 1995;358(4):584–604. doi: 10.1002/cne.903580411.10.1002/cne.9035804117593752Vertes RP. Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience. 2006;142(1):1–20. doi: 10.1016/j.neuroscience.2006.06.027.10.1016/j.neuroscience.2006.06.02716887277Vue TY, Aaker J, Taniguchi A, Kazemzadeh C, Skidmore JM, Martin DM, Martin JF, Treier M, Nakagawa Y. Characterization of progenitor domains in the developing mouse thalamus. J Comp Neurol. 2007;505(1):73–91. doi: 10.1002/cne.21467.10.1002/cne.2146717729296Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, Dwyer S, Smith RL, Green E, Grozeva D, Holmans P, Owen MJ, O’Donovan MC. Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum Mol Genet. 2011;20(2):387–391. doi: 10.1093/hmg/ddq471.10.1093/hmg/ddq47121037240Williams HJ, Norton N, Dwyer S, Moskvina V, Nikolov I, Carroll L, Georgieva L, Williams NM, Morris DW, Quinn EM, Giegling I, Ikeda M, Wood J, Lencz T, Hultman C, Lichtenstein P, Thiselton D, Maher BS, Malhotra AK, Riley B, Kendler KS, Gill M, Sullivan P, Sklar P, Purcell S, Nimgaonkar VL, Kirov G, Holmans P, Corvin A, Rujescu D, Craddock N, Owen MJ, O’Donovan MC, Molecular Genetics of Schizophrenia Collaboration (MGS) International Schizophrenia Consortium (ISC) SGE-p, G. R. O.UP Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. Mol Psychiatry. 2011;16(4):429–441. doi: 10.1038/mp.2010.36.10.1038/mp.2010.36PMC391893420368704Winer JA, Chernock ML, Larue DT, Cheung SW. Descending projections to the inferior colliculus from the posterior thalamus and the auditory cortex in rat, cat, and monkey. Hear Res. 2002;168(1–2):181–195. doi: 10.1016/S0378-5955(02)00489-6.10.1016/S0378-5955(02)00489-612117520Winham SJ, Cuellar-Barboza AB, Oliveros A, McElroy SL, Crow S, Colby C, Choi DS, Chauhan M, Frye M, Biernacka JM. Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2. Mol Psychiatry. 2014;19(9):1010–1016. doi: 10.1038/mp.2013.159.10.1038/mp.2013.15924322204Wisniewska MB, Misztal K, Michowski W, Szczot M, Purta E, Lesniak W, Klejman ME, Dabrowski M, Filipkowski RK, Nagalski A, Mozrzymas JW, Kuznicki J. LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1 g) in thalamic neurons of the adult brain. J Neurosci. 2010;30(14):4957–4969. doi: 10.1523/JNEUROSCI.1425-09.2010.10.1523/JNEUROSCI.1425-09.2010PMC663277520371816Wisniewska MB, Nagalski A, Dabrowski M, Misztal K, Kuznicki J. Novel β-catenin target genes identified in thalamic neurons encode modulators of neuronal excitability. BMC Genom. 2012;13:635. doi: 10.1186/1471-2164-13-635.10.1186/1471-2164-13-635PMC353219323157480Woodward ND, Karbasforoushan H, Heckers S. Thalamocortical dysconnectivity in schizophrenia. Am J Psychiatry. 2012;169(10):1092–1099. doi: 10.1176/appi.ajp.2012.12010056.10.1176/appi.ajp.2012.12010056PMC381030023032387Xu W, Südhof TC. A neural circuit for memory specificity and generalization. Science. 2013;339(6125):1290–1295. doi: 10.1126/science.1229534.10.1126/science.1229534PMC365170023493706Young KA, Holcomb LA, Yazdani U, Hicks PB, German DC. Elevated neuron number in the limbic thalamus in major depression. Am J Psychiatry. 2004;161(7):1270–1277. doi: 10.1176/appi.ajp.161.7.1270.10.1176/appi.ajp.161.7.127015229061Yuge K, Kataoka A, Yoshida AC, Itoh D, Aggarwal M, Mori S, Blackshaw S, Shimogori T. Region-specific gene expression in early postnatal mouse thalamus. J Comp Neurol. 2011;519(3):544–561. doi: 10.1002/cne.22532.10.1002/cne.2253221192083Zhu M, Liu T, Zhang J, Jia S, Tang W, Luo Y. Association between rs1344706 of ZNF804A and schizophrenia: a meta-analysis. Genomics Proteomics Bioinform. 2014;12(6):292–296. doi: 10.1016/j.gpb.2014.10.005.10.1016/j.gpb.2014.10.005PMC441147725526981