Skip to main content
Erschienen in: Brain Structure and Function 5/2014

01.09.2014 | Original Article

Quantitative mapping of the local and extrinsic sources of GABA and Reelin to the layer Ia neuropil in the adult rat neocortex

verfasst von: Tania Ramos-Moreno, Francisco Clascá

Erschienen in: Brain Structure and Function | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Inputs to apical dendritic tufts have been considered to be crucial for associative learning, attention and similar ‘‘feedback’’ interactions and are located in neocortical layer Ia. Excitatory thalamic projections to apical tufts in layer Ia have been well characterized and their role in the cortical circuit has been emphasized. In addition, the neuropil and the extracellular matrix surrounding apical tufts are highly reactive to GABA and to the glycoprotein Reelin, respectively. Recently it has been shown that the GABA inhibition on apical dendrites can reduce the output of pyramidal cells in layer V, however, the origin of 89 % of the symmetric synapses in layer I still remains unknown. In the present study we have systematically analyzed the origin of the GABAergic neuropil in neocortical layer Ia in a qualitative and quantitative manner, and investigated the possible extrinsic origin of the rich extracellular Reelin content of the same layer. We show that the inhibitory inputs in a given spot in layer I come from cortical projections and arise mainly from Martinotti cells located directly under that same spot. Double bouquet and bipolar cells may also project to layer Ia although to a lesser extent and the external globus pallidus and zona incerta provide the remaining inhibitory inputs. Finally, our results suggest that Martinotti cells are also the main source of Reelin in layer Ia. The present data will help in the understanding of the cortical circuit and why it changes in pathological conditions.
Literatur
Zurück zum Zitat Alcantara S, Ruiz M, D’Arcangelo G, Ezan F, de Lecea L, Curran T, Sotelo C, Soriano E (1998) Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse. J Neurosci 18(19):7779–7799PubMed Alcantara S, Ruiz M, D’Arcangelo G, Ezan F, de Lecea L, Curran T, Sotelo C, Soriano E (1998) Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse. J Neurosci 18(19):7779–7799PubMed
Zurück zum Zitat Avendaño C, Llamas A (1984) Thalamic and nonthalamic direct subcortical projections to association areas of the cat’s cerebral cortex. Cortical Integration. Raven Press, New York Avendaño C, Llamas A (1984) Thalamic and nonthalamic direct subcortical projections to association areas of the cat’s cerebral cortex. Cortical Integration. Raven Press, New York
Zurück zum Zitat Avendano C, Stepniewska I, Rausell E, Reinoso-Suarez F (1990) Segregation and heterogeneity of thalamic cell populations projecting to superficial layers of posterior parietal cortex: a retrograde tracer study in cat and monkey. Neuroscience 39(3):547–559PubMedCrossRef Avendano C, Stepniewska I, Rausell E, Reinoso-Suarez F (1990) Segregation and heterogeneity of thalamic cell populations projecting to superficial layers of posterior parietal cortex: a retrograde tracer study in cat and monkey. Neuroscience 39(3):547–559PubMedCrossRef
Zurück zum Zitat Callaway EM (2002) Cell type specificity of local cortical connections. J Neurocytol 31(3–5):231–237PubMedCrossRef Callaway EM (2002) Cell type specificity of local cortical connections. J Neurocytol 31(3–5):231–237PubMedCrossRef
Zurück zum Zitat Cauller L (1995) Layer I of primary sensory neocortex: where top-down converges upon bottom-up. Behav Brain Res 71(1–2):163–170PubMedCrossRef Cauller L (1995) Layer I of primary sensory neocortex: where top-down converges upon bottom-up. Behav Brain Res 71(1–2):163–170PubMedCrossRef
Zurück zum Zitat Cauller LJ, Connors BW (1994) Synaptic physiology of horizontal afferents to layer I in slices of rat SI neocortex. J Neurosci 14(2):751–762PubMed Cauller LJ, Connors BW (1994) Synaptic physiology of horizontal afferents to layer I in slices of rat SI neocortex. J Neurosci 14(2):751–762PubMed
Zurück zum Zitat Cauller LJ, Clancy B, Connors BW (1998) Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I. J Comp Neurol 390(2):297–310PubMedCrossRef Cauller LJ, Clancy B, Connors BW (1998) Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I. J Comp Neurol 390(2):297–310PubMedCrossRef
Zurück zum Zitat Chin J, Massaro CM, Palop JJ, Thwin MT, Yu GQ, Bien-Ly N, Bender A, Mucke L (2007) Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer’s disease. J Neurosci 27(11):2727–2733. doi:10.1523/jneurosci.3758-06.2007 PubMedCrossRef Chin J, Massaro CM, Palop JJ, Thwin MT, Yu GQ, Bien-Ly N, Bender A, Mucke L (2007) Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer’s disease. J Neurosci 27(11):2727–2733. doi:10.​1523/​jneurosci.​3758-06.​2007 PubMedCrossRef
Zurück zum Zitat Clancy B, Cauller LJ (1999) Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex. J Comp Neurol 407(2):275–286PubMedCrossRef Clancy B, Cauller LJ (1999) Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex. J Comp Neurol 407(2):275–286PubMedCrossRef
Zurück zum Zitat Clasca F, Avendano C, Roman-Guindo A, Llamas A, Reinoso-Suarez F (1992) Innervation from the claustrum of the frontal association and motor areas: axonal transport studies in the cat. J Comp Neurol 326(3):402–422. doi:10.1002/cne.903260307 PubMedCrossRef Clasca F, Avendano C, Roman-Guindo A, Llamas A, Reinoso-Suarez F (1992) Innervation from the claustrum of the frontal association and motor areas: axonal transport studies in the cat. J Comp Neurol 326(3):402–422. doi:10.​1002/​cne.​903260307 PubMedCrossRef
Zurück zum Zitat DeFelipe J (1993) Neocortical neuronal diversity: chemical heterogeneity revealed by colocalization studies of classic neurotransmitters, neuropeptides, calcium-binding proteins, and cell surface molecules. Cereb Cortex 3(4):273–289PubMedCrossRef DeFelipe J (1993) Neocortical neuronal diversity: chemical heterogeneity revealed by colocalization studies of classic neurotransmitters, neuropeptides, calcium-binding proteins, and cell surface molecules. Cereb Cortex 3(4):273–289PubMedCrossRef
Zurück zum Zitat DeFelipe J (1997) Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28 K, parvalbumin and calretinin in the neocortex. J Chem Neuroanat 14(1):1–19PubMedCrossRef DeFelipe J (1997) Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28 K, parvalbumin and calretinin in the neocortex. J Chem Neuroanat 14(1):1–19PubMedCrossRef
Zurück zum Zitat Defelipe J, Gonzalez-Albo MC, Del Rio MR, Elston GN (1999) Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey. J Comp Neurol 412(3):515–526PubMedCrossRef Defelipe J, Gonzalez-Albo MC, Del Rio MR, Elston GN (1999) Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey. J Comp Neurol 412(3):515–526PubMedCrossRef
Zurück zum Zitat Dinocourt C, Petanjek Z, Freund TF, Ben-Ari Y, Esclapez M (2003) Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures. J Comp Neurol 459(4):407–425. doi:10.1002/cne.10622 PubMedCrossRef Dinocourt C, Petanjek Z, Freund TF, Ben-Ari Y, Esclapez M (2003) Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures. J Comp Neurol 459(4):407–425. doi:10.​1002/​cne.​10622 PubMedCrossRef
Zurück zum Zitat Duveau V, Madhusudan A, Caleo M, Knuesel I, Fritschy JM (2011) Impaired reelin processing and secretion by Cajal-Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy. Hippocampus 21(9):935–944. doi:10.1002/hipo.20793 PubMed Duveau V, Madhusudan A, Caleo M, Knuesel I, Fritschy JM (2011) Impaired reelin processing and secretion by Cajal-Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy. Hippocampus 21(9):935–944. doi:10.​1002/​hipo.​20793 PubMed
Zurück zum Zitat Fabri M, Manzoni T (1996) Glutamate decarboxylase immunoreactivity in corticocortical projecting neurons of rat somatic sensory cortex. Neuroscience 72(2):435–448PubMedCrossRef Fabri M, Manzoni T (1996) Glutamate decarboxylase immunoreactivity in corticocortical projecting neurons of rat somatic sensory cortex. Neuroscience 72(2):435–448PubMedCrossRef
Zurück zum Zitat Gonchar Y, Burkhalter A (1997) Three distinct families of GABAergic neurons in rat visual cortex. Cereb Cortex 7(4):347–358PubMedCrossRef Gonchar Y, Burkhalter A (1997) Three distinct families of GABAergic neurons in rat visual cortex. Cereb Cortex 7(4):347–358PubMedCrossRef
Zurück zum Zitat Gonchar YA, Johnson PB, Weinberg RJ (1995) GABA-immunopositive neurons in rat neocortex with contralateral projections to S-I. Brain Res 697(1–2):27–34PubMedCrossRef Gonchar YA, Johnson PB, Weinberg RJ (1995) GABA-immunopositive neurons in rat neocortex with contralateral projections to S-I. Brain Res 697(1–2):27–34PubMedCrossRef
Zurück zum Zitat Gritti I, Mainville L, Mancia M, Jones BE (1997) GABAergic and other noncholinergic basal forebrain neurons, together with cholinergic neurons, project to the mesocortex and isocortex in the rat. J Comp Neurol 383(2):163–177PubMedCrossRef Gritti I, Mainville L, Mancia M, Jones BE (1997) GABAergic and other noncholinergic basal forebrain neurons, together with cholinergic neurons, project to the mesocortex and isocortex in the rat. J Comp Neurol 383(2):163–177PubMedCrossRef
Zurück zum Zitat Guidotti A, Auta J, Chen Y, Davis JM, Dong E, Gavin DP, Grayson DR, Matrisciano F, Pinna G, Satta R, Sharma RP, Tremolizzo L, Tueting P (2011) Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 60(7–8):1007–1016. doi:10.1016/j.neuropharm.2010.10.021 PubMedCrossRef Guidotti A, Auta J, Chen Y, Davis JM, Dong E, Gavin DP, Grayson DR, Matrisciano F, Pinna G, Satta R, Sharma RP, Tremolizzo L, Tueting P (2011) Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 60(7–8):1007–1016. doi:10.​1016/​j.​neuropharm.​2010.​10.​021 PubMedCrossRef
Zurück zum Zitat Herkenham M (1986) Cerebral cortex. In: Jones EG, Peters A (eds) New perspectives on the organization and evolution of nonspecific thalamocortical projections. Plenum, New York, pp 403–445 Herkenham M (1986) Cerebral cortex. In: Jones EG, Peters A (eds) New perspectives on the organization and evolution of nonspecific thalamocortical projections. Plenum, New York, pp 403–445
Zurück zum Zitat Jones E (1984) History of cortical citology vol 1. Cerebral cortex, cellular components of the cerebral cortex. Plenum Press, New York Jones E (1984) History of cortical citology vol 1. Cerebral cortex, cellular components of the cerebral cortex. Plenum Press, New York
Zurück zum Zitat Jones EG (2001) The thalamic matrix and thalamocortical synchrony. Trends Neurosci 24(10):595–601PubMedCrossRef Jones EG (2001) The thalamic matrix and thalamocortical synchrony. Trends Neurosci 24(10):595–601PubMedCrossRef
Zurück zum Zitat Kaiser KM, Zilberter Y, Sakmann B (2001) Back-propagating action potentials mediate calcium signalling in dendrites of bitufted interneurons in layer 2/3 of rat somatosensory cortex. J Physiol 535(Pt 1):17–31PubMedCentralPubMedCrossRef Kaiser KM, Zilberter Y, Sakmann B (2001) Back-propagating action potentials mediate calcium signalling in dendrites of bitufted interneurons in layer 2/3 of rat somatosensory cortex. J Physiol 535(Pt 1):17–31PubMedCentralPubMedCrossRef
Zurück zum Zitat Kawaguchi Y (1995) Physiological subgroups of nonpyramidal cells with specific morphological characteristics in layer II/III of rat frontal cortex. J Neurosci 15(4):2638–2655PubMed Kawaguchi Y (1995) Physiological subgroups of nonpyramidal cells with specific morphological characteristics in layer II/III of rat frontal cortex. J Neurosci 15(4):2638–2655PubMed
Zurück zum Zitat Kawaguchi Y, Kondo S (2002) Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex. J Neurocytol 31(3–5):277–287PubMedCrossRef Kawaguchi Y, Kondo S (2002) Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex. J Neurocytol 31(3–5):277–287PubMedCrossRef
Zurück zum Zitat Kawaguchi Y, Kubota Y (1993) Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28k-immunoreactive neurons in layer V of rat frontal cortex. J Neurophysiol 70(1):387–396PubMed Kawaguchi Y, Kubota Y (1993) Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28k-immunoreactive neurons in layer V of rat frontal cortex. J Neurophysiol 70(1):387–396PubMed
Zurück zum Zitat Koester SE, O’Leary DD (1992) Functional classes of cortical projection neurons develop dendritic distinctions by class-specific sculpting of an early common pattern. J Neurosci 12(4):1382–1393PubMed Koester SE, O’Leary DD (1992) Functional classes of cortical projection neurons develop dendritic distinctions by class-specific sculpting of an early common pattern. J Neurosci 12(4):1382–1393PubMed
Zurück zum Zitat Kowianski P, Timmermans JP, Morys J (2001) Differentiation in the immunocytochemical features of intrinsic and cortically projecting neurons in the rat claustrum—combined immunocytochemical and axonal transport study. Brain Res 905(1–2):63–71PubMedCrossRef Kowianski P, Timmermans JP, Morys J (2001) Differentiation in the immunocytochemical features of intrinsic and cortically projecting neurons in the rat claustrum—combined immunocytochemical and axonal transport study. Brain Res 905(1–2):63–71PubMedCrossRef
Zurück zum Zitat Lin CS, Nicolelis MA, Schneider JS, Chapin JK (1990) A major direct GABAergic pathway from zona incerta to neocortex. Science 248(4962):1553–1556PubMedCrossRef Lin CS, Nicolelis MA, Schneider JS, Chapin JK (1990) A major direct GABAergic pathway from zona incerta to neocortex. Science 248(4962):1553–1556PubMedCrossRef
Zurück zum Zitat Lin RC, Nicolelis MA, Chapin JK (1997) Topographic and laminar organizations of the incertocortical pathway in rats. Neuroscience 81(3):641–651PubMedCrossRef Lin RC, Nicolelis MA, Chapin JK (1997) Topographic and laminar organizations of the incertocortical pathway in rats. Neuroscience 81(3):641–651PubMedCrossRef
Zurück zum Zitat Llamas A, Clasca F, Avendano C (1989) Amygdaloid innervation of the frontal cortex in cats. Rev Esp Fisiol 45 Suppl:139–149PubMed Llamas A, Clasca F, Avendano C (1989) Amygdaloid innervation of the frontal cortex in cats. Rev Esp Fisiol 45 Suppl:139–149PubMed
Zurück zum Zitat Martinez-Cerdeno V, Clasca F (2002) Reelin immunoreactivity in the adult neocortex: a comparative study in rodents, carnivores, and non-human primates. Brain Res Bull 57(3–4):485–488PubMedCrossRef Martinez-Cerdeno V, Clasca F (2002) Reelin immunoreactivity in the adult neocortex: a comparative study in rodents, carnivores, and non-human primates. Brain Res Bull 57(3–4):485–488PubMedCrossRef
Zurück zum Zitat Maunsell JH, van Essen DC (1983) The connections of the middle temporal visual area (MT) and their relationship to a cortical hierarchy in the macaque monkey. J Neurosci 3(12):2563–2586PubMed Maunsell JH, van Essen DC (1983) The connections of the middle temporal visual area (MT) and their relationship to a cortical hierarchy in the macaque monkey. J Neurosci 3(12):2563–2586PubMed
Zurück zum Zitat McDonald CT, Burkhalter A (1993) Organization of long-range inhibitory connections with rat visual cortex. J Neurosci 13(2):768–781PubMed McDonald CT, Burkhalter A (1993) Organization of long-range inhibitory connections with rat visual cortex. J Neurosci 13(2):768–781PubMed
Zurück zum Zitat Mitchell BD, Cauller LJ (2001) Corticocortical and thalamocortical projections to layer I of the frontal neocortex in rats. Brain Res 921(1–2):68–77PubMedCrossRef Mitchell BD, Cauller LJ (2001) Corticocortical and thalamocortical projections to layer I of the frontal neocortex in rats. Brain Res 921(1–2):68–77PubMedCrossRef
Zurück zum Zitat Nicolelis MA, Chapin JK, Lin RC (1995) Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat. Neuroscience 65(2):609–631PubMedCrossRef Nicolelis MA, Chapin JK, Lin RC (1995) Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat. Neuroscience 65(2):609–631PubMedCrossRef
Zurück zum Zitat Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego
Zurück zum Zitat Reep RL (2000) Cortical layer VII and persistent subplate cells in mammalian brains. Brain Behav Evol 56(4):212–234PubMedCrossRef Reep RL (2000) Cortical layer VII and persistent subplate cells in mammalian brains. Brain Behav Evol 56(4):212–234PubMedCrossRef
Zurück zum Zitat Reep RL, Goodwin GS (1988) Layer VII of rodent cerebral cortex. Neurosci Lett 90(1–2):15–20PubMedCrossRef Reep RL, Goodwin GS (1988) Layer VII of rodent cerebral cortex. Neurosci Lett 90(1–2):15–20PubMedCrossRef
Zurück zum Zitat Rubio-Garrido P, Perez-de-Manzo F, Clasca F (2007) Calcium-binding proteins as markers of layer-I projecting vs. deep layer-projecting thalamocortical neurons: a double-labeling analysis in the rat. Neuroscience 149(1):242–250. doi:10.1016/j.neuroscience.2007.07.036 Rubio-Garrido P, Perez-de-Manzo F, Clasca F (2007) Calcium-binding proteins as markers of layer-I projecting vs. deep layer-projecting thalamocortical neurons: a double-labeling analysis in the rat. Neuroscience 149(1):242–250. doi:10.​1016/​j.​neuroscience.​2007.​07.​036
Zurück zum Zitat Rubio-Garrido P, Perez-de-Manzo F, Porrero C, Galazo MJ, Clasca F (2009) Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent. Cereb Cortex 19(10):2380–2395. doi:10.1093/cercor/bhn259 PubMedCrossRef Rubio-Garrido P, Perez-de-Manzo F, Porrero C, Galazo MJ, Clasca F (2009) Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent. Cereb Cortex 19(10):2380–2395. doi:10.​1093/​cercor/​bhn259 PubMedCrossRef
Zurück zum Zitat Saez-Valero J, Costell M, Sjogren M, Andreasen N, Blennow K, Luque JM (2003) Altered levels of cerebrospinal fluid reelin in frontotemporal dementia and Alzheimer’s disease. J Neurosci Res 72(1):132–136. doi:10.1002/jnr.10554 PubMedCrossRef Saez-Valero J, Costell M, Sjogren M, Andreasen N, Blennow K, Luque JM (2003) Altered levels of cerebrospinal fluid reelin in frontotemporal dementia and Alzheimer’s disease. J Neurosci Res 72(1):132–136. doi:10.​1002/​jnr.​10554 PubMedCrossRef
Zurück zum Zitat Sarter M, Bruno JP (2002) The neglected constituent of the basal forebrain corticopetal projection system: GABAergic projections. Eur J Neurosci 15(12):1867–1873PubMedCrossRef Sarter M, Bruno JP (2002) The neglected constituent of the basal forebrain corticopetal projection system: GABAergic projections. Eur J Neurosci 15(12):1867–1873PubMedCrossRef
Zurück zum Zitat Shepherd GM, Brayton RK, Miller JP, Segev I, Rinzel J, Rall W (1985) Signal enhancement in distal cortical dendrites by means of interactions between active dendritic spines. Proc Natl Acad Sci USA 82(7):2192–2195PubMedCentralPubMedCrossRef Shepherd GM, Brayton RK, Miller JP, Segev I, Rinzel J, Rall W (1985) Signal enhancement in distal cortical dendrites by means of interactions between active dendritic spines. Proc Natl Acad Sci USA 82(7):2192–2195PubMedCentralPubMedCrossRef
Zurück zum Zitat Shlosberg D, Patrick SL, Buskila Y, Amitai Y (2003) Inhibitory effect of mouse neocortex layer I on the underlying cellular network. Eur J Neurosci 18(10):2751–2759PubMedCrossRef Shlosberg D, Patrick SL, Buskila Y, Amitai Y (2003) Inhibitory effect of mouse neocortex layer I on the underlying cellular network. Eur J Neurosci 18(10):2751–2759PubMedCrossRef
Zurück zum Zitat Vogt B (1991) The role of layer I in cortical function. In: Peters A, Jones EG (eds) vol 9. Plenum Press, New York Vogt B (1991) The role of layer I in cortical function. In: Peters A, Jones EG (eds) vol 9. Plenum Press, New York
Zurück zum Zitat Zhang X, Hannesson DK, Saucier DM, Wallace AE, Howland J, Corcoran ME (2001) Susceptibility to kindling and neuronal connections of the anterior claustrum. J Neurosci 21(10):3674–3687PubMed Zhang X, Hannesson DK, Saucier DM, Wallace AE, Howland J, Corcoran ME (2001) Susceptibility to kindling and neuronal connections of the anterior claustrum. J Neurosci 21(10):3674–3687PubMed
Metadaten
Titel
Quantitative mapping of the local and extrinsic sources of GABA and Reelin to the layer Ia neuropil in the adult rat neocortex
verfasst von
Tania Ramos-Moreno
Francisco Clascá
Publikationsdatum
01.09.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 5/2014
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-013-0591-x

Weitere Artikel der Ausgabe 5/2014

Brain Structure and Function 5/2014 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.