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Erschienen in: Brain Structure and Function 3/2014

01.05.2014 | Original Article

Distribution of different isoforms of receptor protein tyrosine phosphatase γ (Ptprg-RPTP γ) in adult mouse brain: upregulation during neuroinflammation

verfasst von: Erika Lorenzetto, Elisabetta Moratti, Marzia Vezzalini, Sheila Harroch, Claudio Sorio, Mario Buffelli

Erschienen in: Brain Structure and Function | Ausgabe 3/2014

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Abstract

The receptor protein tyrosine phosphatase γ (Ptprg-RPTPγ) is a receptor protein widely expressed in many tissues, including the central nervous system (CNS). Several RPTPγ isoforms are expressed in the brain during development and in adulthood, but their distribution and role are unknown. In this study, we investigated the distribution of some RPTPγ isoforms in the adult brain using antibodies against the epitopes localized in the C- and in the N-terminal domains of the full length isoform of RPTPγ. We found a predominant and widespread neuronal positivity throughout the neocortex, hippocampus, striatum and in many nuclei of the brainstem and cerebellum. At least 2 distinct isoforms that can co-exist in various compartments in the same cell are detectable in different neuron types. Immunopositivity for epitopes located in both the N- and C-terminus domains were found in the neuropil of cortical and hippocampal neurons, whereas the N-terminal domain positivity was found in the soma, often without colocalization with its C-terminal counterpart. Among glial cells, some protoplasmic and perivascular astrocytes and the cerebellar Bergmann glia, express RPTPγ. The astrocytic expression of RPTPγ and putative processing isoforms of 120 and 80 kDa increases during neuroinflammation, in particular 24 h after LPS treatment. Activated astrocytes were found to be strongly positive for RPTPγ also in a mice model of Alzheimer’s disease. Our results confirm previous findings and enrich the current knowledge of RPTPγ distribution in the CNS, highlighting a role of RPTPγ during neuroinflammation processes.
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Literatur
Zurück zum Zitat Barnea G, Silvennoinen O, Shaanan B, Honegger AM, Canoll PD, D’Eustachio P, Morse B, Levy JB, Laforgia S, Huebner K et al (1993) Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases. Mol Cell Biol 13(3):1497–1506PubMedCentralPubMed Barnea G, Silvennoinen O, Shaanan B, Honegger AM, Canoll PD, D’Eustachio P, Morse B, Levy JB, Laforgia S, Huebner K et al (1993) Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases. Mol Cell Biol 13(3):1497–1506PubMedCentralPubMed
Zurück zum Zitat Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I et al (2009). Large-scale structural analysis of the classical human protein tyrosine phosphatome [Research Support, Non-U.S. Gov’t]. Cell 136(2):352–363. doi:10.1016/j.cell.2008.11.038 Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I et al (2009). Large-scale structural analysis of the classical human protein tyrosine phosphatome [Research Support, Non-U.S. Gov’t]. Cell 136(2):352–363. doi:10.​1016/​j.​cell.​2008.​11.​038
Zurück zum Zitat Bouyain S, Watkins DJ (2010) The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules. Proc Natl Acad Sci USA 107(6):2443–2448. doi:10.1073/pnas.0911235107 Bouyain S, Watkins DJ (2010) The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules. Proc Natl Acad Sci USA 107(6):2443–2448. doi:10.​1073/​pnas.​0911235107
Zurück zum Zitat Candelario-Jalil E, Yang Y, Rosenberg GA (2009) Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 158(3):983–994. doi:10.1016/j.neuroscience.2008.06.025 Candelario-Jalil E, Yang Y, Rosenberg GA (2009) Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 158(3):983–994. doi:10.​1016/​j.​neuroscience.​2008.​06.​025
Zurück zum Zitat Cottrell CE, Bir N, Varga E, Alvarez CE, Bouyain S, Zernzach R et al (2011) Contactin 4 as an autism susceptibility locus [Case Reports Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.S.]. Autism Res 4(3):189–199. doi:10.1002/aur.184 PubMedCentralPubMedCrossRef Cottrell CE, Bir N, Varga E, Alvarez CE, Bouyain S, Zernzach R et al (2011) Contactin 4 as an autism susceptibility locus [Case Reports Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.S.]. Autism Res 4(3):189–199. doi:10.​1002/​aur.​184 PubMedCentralPubMedCrossRef
Zurück zum Zitat Crocker SJ, Milner R, Pham-Mitchell N, Campbell IL (2006) Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells. J Neurochem 98 (3):812–823. doi:10.1111/j.1471-4159.2006.03927.x Crocker SJ, Milner R, Pham-Mitchell N, Campbell IL (2006) Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells. J Neurochem 98 (3):812–823. doi:10.​1111/​j.​1471-4159.​2006.​03927.​x
Zurück zum Zitat Dabrowski A, Umemori H (2011) Orchestrating the synaptic network by tyrosine phosphorylation signalling. J Biochem 149(6):641–653. doi:10.1093/jb/mvr047 Dabrowski A, Umemori H (2011) Orchestrating the synaptic network by tyrosine phosphorylation signalling. J Biochem 149(6):641–653. doi:10.​1093/​jb/​mvr047
Zurück zum Zitat Della Peruta M, Martinelli G, Moratti E, Pintani D, Vezzalini M, Mafficini A, Grafone T, Iacobucci I, Soverini S, Murineddu M, Vinante F, Tecchio C, Piras G, Gabbas A, Monne M, Sorio C (2010) Protein tyrosine phosphatase receptor type gamma is a functional tumor suppressor gene specifically downregulated in chronic myeloid leukemia. Cancer Res 70(21):8896–8906. doi:10.1158/0008-5472.CAN-10-0258 PubMedCrossRef Della Peruta M, Martinelli G, Moratti E, Pintani D, Vezzalini M, Mafficini A, Grafone T, Iacobucci I, Soverini S, Murineddu M, Vinante F, Tecchio C, Piras G, Gabbas A, Monne M, Sorio C (2010) Protein tyrosine phosphatase receptor type gamma is a functional tumor suppressor gene specifically downregulated in chronic myeloid leukemia. Cancer Res 70(21):8896–8906. doi:10.​1158/​0008-5472.​CAN-10-0258 PubMedCrossRef
Zurück zum Zitat Faissner A, Heck N, Dobbertin A, Garwood J (2006) DSD-1-Proteoglycan/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues. Adv Exp Med Biol 557:25–53. doi:10.1007/0-387-30128-3_3 PubMedCrossRef Faissner A, Heck N, Dobbertin A, Garwood J (2006) DSD-1-Proteoglycan/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues. Adv Exp Med Biol 557:25–53. doi:10.​1007/​0-387-30128-3_​3 PubMedCrossRef
Zurück zum Zitat Gottschall PE, Deb S (1996) Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. Neuroimmunomodulation 3(2–3):69–75PubMedCrossRef Gottschall PE, Deb S (1996) Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. Neuroimmunomodulation 3(2–3):69–75PubMedCrossRef
Zurück zum Zitat Gottschall PE, Yu X (1995) Cytokines regulate gelatinase A and B (matrix metalloproteinase 2 and 9) activity in cultured rat astrocytes. J Neurochem 64(4):1513–1520PubMed Gottschall PE, Yu X (1995) Cytokines regulate gelatinase A and B (matrix metalloproteinase 2 and 9) activity in cultured rat astrocytes. J Neurochem 64(4):1513–1520PubMed
Zurück zum Zitat Hashemi H, Hurley M, Gibson A, Panova V, Tchetchelnitski V, Barr A, Stoker AW (2011) Receptor tyrosine phosphatase PTPgamma is a regulator of spinal cord neurogenesis. Mol Cell Neurosci 46(2):469–482. doi:10.1016/j.mcn.2010.11.012 Hashemi H, Hurley M, Gibson A, Panova V, Tchetchelnitski V, Barr A, Stoker AW (2011) Receptor tyrosine phosphatase PTPgamma is a regulator of spinal cord neurogenesis. Mol Cell Neurosci 46(2):469–482. doi:10.​1016/​j.​mcn.​2010.​11.​012
Zurück zum Zitat Hayashi N, Oohira A, Miyata S (2005) Synaptic localization of receptor-type protein tyrosine phosphatase zeta/beta in the cerebral and hippocampal neurons of adult rats. Brain Res 1050(1–2):163–169. doi:10.1016/j.brainres.2005.05.047 Hayashi N, Oohira A, Miyata S (2005) Synaptic localization of receptor-type protein tyrosine phosphatase zeta/beta in the cerebral and hippocampal neurons of adult rats. Brain Res 1050(1–2):163–169. doi:10.​1016/​j.​brainres.​2005.​05.​047
Zurück zum Zitat Kawachi H, Tamura H, Watakabe I, Shintani T, Maeda N, Noda M (1999) Protein tyrosine phosphatase zeta/RPTPbeta interacts with PSD-95/SAP90 family [Research Support, Non-U.S. Gov’t]. Brain Res Mol Brain Res 72(1):47–54PubMedCrossRef Kawachi H, Tamura H, Watakabe I, Shintani T, Maeda N, Noda M (1999) Protein tyrosine phosphatase zeta/RPTPbeta interacts with PSD-95/SAP90 family [Research Support, Non-U.S. Gov’t]. Brain Res Mol Brain Res 72(1):47–54PubMedCrossRef
Zurück zum Zitat Kwon MS, Seo YJ, Choi SM, Won MH, Lee JK, Park SH, Jung JS, Sim YB, Suh HW (2010) The time-dependent effect of lipopolysaccharide on kainic acid-induced neuronal death in hippocampal CA3 region: possible involvement of cytokines via glucocorticoid. Neuroscience 165(4):1333–1344. doi:10.1016/j.neuroscience.2009.11.060 Kwon MS, Seo YJ, Choi SM, Won MH, Lee JK, Park SH, Jung JS, Sim YB, Suh HW (2010) The time-dependent effect of lipopolysaccharide on kainic acid-induced neuronal death in hippocampal CA3 region: possible involvement of cytokines via glucocorticoid. Neuroscience 165(4):1333–1344. doi:10.​1016/​j.​neuroscience.​2009.​11.​060
Zurück zum Zitat Lamprianou S, Harroch S (2006) Receptor protein tyrosine phosphatase from stem cells to mature glial cells of the central nervous system. J Mol Neurosci 29(3):241–255. doi:10.1385/JMN:29:3:241 Lamprianou S, Harroch S (2006) Receptor protein tyrosine phosphatase from stem cells to mature glial cells of the central nervous system. J Mol Neurosci 29(3):241–255. doi:10.​1385/​JMN:​29:​3:​241
Zurück zum Zitat Lamprianou S, Vacaresse N, Suzuki Y, Meziane H, Buxbaum JD, Schlessinger J, Harroch S (2006) Receptor protein tyrosine phosphatase gamma is a marker for pyramidal cells and sensory neurons in the nervous system and is not necessary for normal development. Mol Cell Biol 26(13):5106–5119. doi:10.1128/MCB.00101-06 Lamprianou S, Vacaresse N, Suzuki Y, Meziane H, Buxbaum JD, Schlessinger J, Harroch S (2006) Receptor protein tyrosine phosphatase gamma is a marker for pyramidal cells and sensory neurons in the nervous system and is not necessary for normal development. Mol Cell Biol 26(13):5106–5119. doi:10.​1128/​MCB.​00101-06
Zurück zum Zitat Lamprianou S, Chatzopoulou E, Thomas JL, Bouyain S, Harroch S (2011) A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells. Proc Natl Acad Sci USA 108(42):17498–17503. doi:10.1073/pnas.1108774108 Lamprianou S, Chatzopoulou E, Thomas JL, Bouyain S, Harroch S (2011) A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells. Proc Natl Acad Sci USA 108(42):17498–17503. doi:10.​1073/​pnas.​1108774108
Zurück zum Zitat Lee WJ, Shin CY, Yoo BK, Ryu JR, Choi EY, Cheong JH, Ryu JH, Ko KH (2003) Induction of matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide-stimulated primary astrocytes is mediated by extracellular signal-regulated protein kinase 1/2 (Erk1/2). Glia 41(1):15–24. doi:10.1002/glia.10131 PubMedCrossRef Lee WJ, Shin CY, Yoo BK, Ryu JR, Choi EY, Cheong JH, Ryu JH, Ko KH (2003) Induction of matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide-stimulated primary astrocytes is mediated by extracellular signal-regulated protein kinase 1/2 (Erk1/2). Glia 41(1):15–24. doi:10.​1002/​glia.​10131 PubMedCrossRef
Zurück zum Zitat Mafficini A, Vezzalini M, Zamai L, Galeotti L, Bergamini G, Della Peruta M, Melotti P, Sorio C (2007) Protein tyrosine phosphatase gamma (PTPgamma) is a novel leukocyte marker highly expressed by CD34 precursors. Biomark Insights 2:218–225PubMedCentralPubMed Mafficini A, Vezzalini M, Zamai L, Galeotti L, Bergamini G, Della Peruta M, Melotti P, Sorio C (2007) Protein tyrosine phosphatase gamma (PTPgamma) is a novel leukocyte marker highly expressed by CD34 precursors. Biomark Insights 2:218–225PubMedCentralPubMed
Zurück zum Zitat Nishiwaki T, Maeda N, Noda M (1998) Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta isoforms. J Biochem 123(3):458–467PubMedCrossRef Nishiwaki T, Maeda N, Noda M (1998) Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta isoforms. J Biochem 123(3):458–467PubMedCrossRef
Zurück zum Zitat Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26(40):10129–10140. doi:10.1523/JNEUROSCI.1202-06.2006 Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26(40):10129–10140. doi:10.​1523/​JNEUROSCI.​1202-06.​2006
Zurück zum Zitat Romero-Calvo I, Ocon B, Martinez-Moya P, Suarez MD, Zarzuelo A, Martinez-Augustin O, de Medina FS (2010) Reversible Ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem 401(2):318–320. doi:10.1016/j.ab.2010.02.036 Romero-Calvo I, Ocon B, Martinez-Moya P, Suarez MD, Zarzuelo A, Martinez-Augustin O, de Medina FS (2010) Reversible Ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem 401(2):318–320. doi:10.​1016/​j.​ab.​2010.​02.​036
Zurück zum Zitat Sakurai T, Friedlander DR, Grumet M (1996) Expression of polypeptide variants of receptor-type protein tyrosine phosphatase beta: the secreted form, phosphacan, increases dramatically during embryonic development and modulates glial cell behavior in vitro [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.]. J Neurosci Res43(6):694–706. doi:10.1002/(SICI)1097-4547(19960315)43:6<694::AID-JNR6>3.0.CO;2-9 Sakurai T, Friedlander DR, Grumet M (1996) Expression of polypeptide variants of receptor-type protein tyrosine phosphatase beta: the secreted form, phosphacan, increases dramatically during embryonic development and modulates glial cell behavior in vitro [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.]. J Neurosci Res43(6):694–706. doi:10.​1002/​(SICI)1097-4547(19960315)43:​6<694:​:​AID-JNR6>3.​0.​CO;2-9
Zurück zum Zitat Sandvig A, Berry M, Barrett LB, Butt A, Logan A (2004) Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration [Review]. Glia 46(3):225–251. doi:10.1002/glia.10315 Sandvig A, Berry M, Barrett LB, Butt A, Logan A (2004) Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration [Review]. Glia 46(3):225–251. doi:10.​1002/​glia.​10315
Zurück zum Zitat Schumann G, Fiebich BL, Menzel D, Hull M, Butcher R, Nielsen P, Bauer J (1998) Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells. Brain Res Mol Brain Res 62(1):56–64 Schumann G, Fiebich BL, Menzel D, Hull M, Butcher R, Nielsen P, Bauer J (1998) Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells. Brain Res Mol Brain Res 62(1):56–64
Zurück zum Zitat Shintani T, Maeda N, Nishiwaki T, Noda M (1997) Characterization of rat receptor-like protein tyrosine phosphatase gamma isoforms. Biochem Biophys Res Commun 230(2):419–425. doi:10.1006/bbrc.1996.5973 Shintani T, Maeda N, Nishiwaki T, Noda M (1997) Characterization of rat receptor-like protein tyrosine phosphatase gamma isoforms. Biochem Biophys Res Commun 230(2):419–425. doi:10.​1006/​bbrc.​1996.​5973
Zurück zum Zitat Shintani T, Watanabe E, Maeda N, Noda M (1998) Neurons as well as astrocytes express proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta: analysis of mice in which the PTPzeta/RPTPbeta gene was replaced with the LacZ gene. Neurosci Lett 247(2–3):135–138PubMedCrossRef Shintani T, Watanabe E, Maeda N, Noda M (1998) Neurons as well as astrocytes express proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta: analysis of mice in which the PTPzeta/RPTPbeta gene was replaced with the LacZ gene. Neurosci Lett 247(2–3):135–138PubMedCrossRef
Zurück zum Zitat Shintani T, Maeda N, Noda M (2001) Receptor-like protein tyrosine phosphatase gamma (RPTPgamma), but not PTPzeta/RPTPbeta, inhibits nerve-growth-factor-induced neurite outgrowth in PC12D cells. Dev Neurosci 23(1):55–69 Shintani T, Maeda N, Noda M (2001) Receptor-like protein tyrosine phosphatase gamma (RPTPgamma), but not PTPzeta/RPTPbeta, inhibits nerve-growth-factor-induced neurite outgrowth in PC12D cells. Dev Neurosci 23(1):55–69
Zurück zum Zitat Sorio C, Mendrola J, Lou Z, LaForgia S, Croce CM, Huebner K (1995) Characterization of the receptor protein tyrosine phosphatase gene product PTP gamma: binding and activation by triphosphorylated nucleosides. Cancer Res 55(21):4855–4864PubMed Sorio C, Mendrola J, Lou Z, LaForgia S, Croce CM, Huebner K (1995) Characterization of the receptor protein tyrosine phosphatase gene product PTP gamma: binding and activation by triphosphorylated nucleosides. Cancer Res 55(21):4855–4864PubMed
Zurück zum Zitat Tanaka M, Maeda N, Noda M, Marunouchi T (2003) A chondroitin sulfate proteoglycan PTPzeta/RPTPbeta regulates the morphogenesis of Purkinje cell dendrites in the developing cerebellum. J Neurosci 23(7):2804–2814 Tanaka M, Maeda N, Noda M, Marunouchi T (2003) A chondroitin sulfate proteoglycan PTPzeta/RPTPbeta regulates the morphogenesis of Purkinje cell dendrites in the developing cerebellum. J Neurosci 23(7):2804–2814
Zurück zum Zitat Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7(11):833–846. doi:10.1038/nrm2039 Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7(11):833–846. doi:10.​1038/​nrm2039
Zurück zum Zitat Vezzalini M, Mombello A, Menestrina F, Mafficini A, Della Peruta M, van Niekerk C, Barbareschi M, Scarpa A, Sorio C (2007) Expression of transmembrane protein tyrosine phosphatase gamma (PTPgamma) in normal and neoplastic human tissues. Histopathology 50(5):615–628. doi:10.1111/j.1365-2559.2007.02661.x Vezzalini M, Mombello A, Menestrina F, Mafficini A, Della Peruta M, van Niekerk C, Barbareschi M, Scarpa A, Sorio C (2007) Expression of transmembrane protein tyrosine phosphatase gamma (PTPgamma) in normal and neoplastic human tissues. Histopathology 50(5):615–628. doi:10.​1111/​j.​1365-2559.​2007.​02661.​x
Zurück zum Zitat Zhang W, Savelieva KV, Tran D, Pogorelov VM, Cullinan EB, Backer KB, Platt KA, Hu S, Rajan I, Xu N, Lanthorn TH (2012) Characterization of PTPRG in knockdown and phosphatase-inactive mutant mice and substrate trapping analysis of PTPRG in mammalian cells. PLoS ONE 7(9):e45500. doi:10.1371/journal.pone.0045500 PubMedCentralPubMedCrossRef Zhang W, Savelieva KV, Tran D, Pogorelov VM, Cullinan EB, Backer KB, Platt KA, Hu S, Rajan I, Xu N, Lanthorn TH (2012) Characterization of PTPRG in knockdown and phosphatase-inactive mutant mice and substrate trapping analysis of PTPRG in mammalian cells. PLoS ONE 7(9):e45500. doi:10.​1371/​journal.​pone.​0045500 PubMedCentralPubMedCrossRef
Metadaten
Titel
Distribution of different isoforms of receptor protein tyrosine phosphatase γ (Ptprg-RPTP γ) in adult mouse brain: upregulation during neuroinflammation
verfasst von
Erika Lorenzetto
Elisabetta Moratti
Marzia Vezzalini
Sheila Harroch
Claudio Sorio
Mario Buffelli
Publikationsdatum
01.05.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 3/2014
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-013-0541-7

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