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Erschienen in: Brain Structure and Function 1/2019

09.10.2018 | Original Article

Gene expression and neurochemical characterization of the rostromedial tegmental nucleus (RMTg) in rats and mice

verfasst von: Rachel J. Smith, Peter J. Vento, Ying S. Chao, Cameron H. Good, Thomas C. Jhou

Erschienen in: Brain Structure and Function | Ausgabe 1/2019

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Abstract

The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic structure identified in 2009 that receives strong inputs from the lateral habenula and other sources, sends dense inhibitory projections to midbrain dopamine (DA) neurons, and plays increasingly recognized roles in aversive learning, addiction, and other motivated behaviors. In general, little is known about the genetic identity of these neurons. However, recent work has identified the transcription factor FoxP1 as enhanced in the mouse RMTg (Lahti et al. in Development 143(3):516–529, 2016). Hence, in the current study, we used RNA sequencing to identify genes significantly enhanced in the rat RMTg as compared to adjacent VTA, and then examined the detailed distribution of two genes in particular, prepronociceptin (Pnoc) and FoxP1. In rats and mice, both Pnoc and FoxP1 were expressed at high levels in the RMTg and colocalized strongly with previously established RMTg markers. FoxP1 was particularly selective for RMTg neurons, as it was absent in most adjacent brain regions. We used these gene expression patterns to refine the anatomic characterization of RMTg in rats, extend this characterization to mice, and show that optogenetic manipulation of RMTg in mice bidirectionally modulates real-time place preference. Hence, RMTg neurons in both rats and mice exhibit distinct genetic profiles that correlate with their distinct connectivity and function.
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Literatur
Zurück zum Zitat Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57(1):289–300 Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57(1):289–300
Zurück zum Zitat Colussi-Mas J, Geisler S, Zimmer L, Zahm DS, Berod A (2007) Activation of afferents to the ventral tegmental area in response to acute amphetamine: a double-labelling study. Eur J Neurosci 26(4):1011–1025CrossRefPubMedPubMedCentral Colussi-Mas J, Geisler S, Zimmer L, Zahm DS, Berod A (2007) Activation of afferents to the ventral tegmental area in response to acute amphetamine: a double-labelling study. Eur J Neurosci 26(4):1011–1025CrossRefPubMedPubMedCentral
Zurück zum Zitat Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ (1991) Two genes encode distinct glutamate decarboxylases. Neuron 7(1):91–100CrossRefPubMed Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ (1991) Two genes encode distinct glutamate decarboxylases. Neuron 7(1):91–100CrossRefPubMed
Zurück zum Zitat Lahti L, Haugas M, Tikker L, Airavaara M, Voutilainen MH, Anttila J, Kumar S, Inkinen C, Salminen M, Partanen J (2016) Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei. Development 143(3):516–529. https://doi.org/10.1242/dev.129957 CrossRefPubMed Lahti L, Haugas M, Tikker L, Airavaara M, Voutilainen MH, Anttila J, Kumar S, Inkinen C, Salminen M, Partanen J (2016) Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei. Development 143(3):516–529. https://​doi.​org/​10.​1242/​dev.​129957 CrossRefPubMed
Zurück zum Zitat Lavezzi H, Parsley K, Ariel M, Zahm DS (2010) Fos expression in a projection from the rostromedial tegmental nucleus (RMTg) to the pars dissipata of the pedunculopontine tegmental nucleus (PPTg) following administration of methamphetamine in the rat. Soci Neurosci Abstr 491.494 Lavezzi H, Parsley K, Ariel M, Zahm DS (2010) Fos expression in a projection from the rostromedial tegmental nucleus (RMTg) to the pars dissipata of the pedunculopontine tegmental nucleus (PPTg) following administration of methamphetamine in the rat. Soci Neurosci Abstr 491.494
Zurück zum Zitat Lein 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 (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445(7124):168–176. https://doi.org/10.1038/nature05453 CrossRefPubMed Lein 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 (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445(7124):168–176. https://​doi.​org/​10.​1038/​nature05453 CrossRefPubMed
Zurück zum Zitat Morales MF, Wang H, Zhang P, Lehrmann E, Wood WH, Becker KG, Ikemoto S, Jhou TC (2011) Expression of prepronociceptin mRNA in the rostromedial tegmental nucleus (RMTg). In: Program No. 201.20. 2011 Neuroscience Meeting Planner. Society for Neuroscience, Washington, DC Morales MF, Wang H, Zhang P, Lehrmann E, Wood WH, Becker KG, Ikemoto S, Jhou TC (2011) Expression of prepronociceptin mRNA in the rostromedial tegmental nucleus (RMTg). In: Program No. 201.20. 2011 Neuroscience Meeting Planner. Society for Neuroscience, Washington, DC
Zurück zum Zitat Neal CR Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Watson SJ Jr (1999) Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat. J Comp Neurol 406(4):503–547CrossRefPubMed Neal CR Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Watson SJ Jr (1999) Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat. J Comp Neurol 406(4):503–547CrossRefPubMed
Zurück zum Zitat Oakman SA, Faris PL, Kerr PE, Cozzari C, Hartman BK (1995) Distribution of pontomesencephalic cholinergic neurons projecting to substantia nigra differs significantly from those projecting to ventral tegmental area. J Neurosci 15(9):5859–5869CrossRefPubMedPubMedCentral Oakman SA, Faris PL, Kerr PE, Cozzari C, Hartman BK (1995) Distribution of pontomesencephalic cholinergic neurons projecting to substantia nigra differs significantly from those projecting to ventral tegmental area. J Neurosci 15(9):5859–5869CrossRefPubMedPubMedCentral
Zurück zum Zitat Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2nd edn. Academic Press, London Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2nd edn. Academic Press, London
Zurück zum Zitat Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, London Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, London
Zurück zum Zitat Perrotti LI, Bolanos CA, Choi KH, Russo SJ, Edwards S, Ulery PG, Wallace DL, Self DW, Nestler EJ, Barrot M (2005) DeltaFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment. Eur J Neurosci 21(10):2817–2824CrossRefPubMed Perrotti LI, Bolanos CA, Choi KH, Russo SJ, Edwards S, Ulery PG, Wallace DL, Self DW, Nestler EJ, Barrot M (2005) DeltaFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment. Eur J Neurosci 21(10):2817–2824CrossRefPubMed
Zurück zum Zitat Simmons DM, Arriza JL, Swanson LW (1989) A complete protocol for in situ hybridization of messenger RNAs in brain and other tissues with radio-labeled single-stranded RNA probes. J Histotechnol 3:169–181CrossRef Simmons DM, Arriza JL, Swanson LW (1989) A complete protocol for in situ hybridization of messenger RNAs in brain and other tissues with radio-labeled single-stranded RNA probes. J Histotechnol 3:169–181CrossRef
Zurück zum Zitat Zangen A, Ikemoto S, Zadina JE, Wise RA (2002) Rewarding and psychomotor stimulant effects of endomorphin-1: anteroposterior differences within the ventral tegmental area and lack of effect in nucleus accumbens. J Neurosci 22(16):7225–7233CrossRefPubMedPubMedCentral Zangen A, Ikemoto S, Zadina JE, Wise RA (2002) Rewarding and psychomotor stimulant effects of endomorphin-1: anteroposterior differences within the ventral tegmental area and lack of effect in nucleus accumbens. J Neurosci 22(16):7225–7233CrossRefPubMedPubMedCentral
Metadaten
Titel
Gene expression and neurochemical characterization of the rostromedial tegmental nucleus (RMTg) in rats and mice
verfasst von
Rachel J. Smith
Peter J. Vento
Ying S. Chao
Cameron H. Good
Thomas C. Jhou
Publikationsdatum
09.10.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 1/2019
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-018-1761-7

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