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Thomas Deller - One of the best experts on this subject based on the ideXlab platform.
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understanding the role of synaptopodin and the Spine Apparatus in hebbian synaptic plasticity new perspectives and the need for computational modeling
Neurobiology of Learning and Memory, 2017Co-Authors: Peter Jedlicka, Thomas DellerAbstract:Synaptopodin (SP) is a proline-rich actin-associated protein essential for the formation of a Spine Apparatus (SA) in dendritic Spines. The SA consists of stacks of smooth endoplasmic reticulum (sER) contiguous with the meshwork of somatodendritic ER. Spines of SP-deficient mice contain sER but no SA, demonstrating that SP is necessary for the assembly of ER cisterns into the more complex SA organelle. Although the SA was described decades ago, its function was difficult to investigate and remained elusive, in part because reliable markers for the SA were missing. After SP was identified as an essential component and a reliable marker of the SA, a role of SP/SA in hippocampal synaptic plasticity could be firmly established using loss-of-function approaches. Further studies revealed that SP/SA participate in the regulation of Ca2+-dependent Spine-specific Hebbian plasticity and in activity-dependent changes in the Spine actin cytoskeleton. In this review we are summarizing recent progress made on SP/SA in Hebbian plasticity and discuss open questions such as causality, spatiotemporal dynamics and complementarity of SP/SA-dependent mechanisms. We are proposing that computational modeling of Spine Ca2+-signaling and actin remodeling pathways could address some of these issues and could indicate future research directions. Moreover, reaction-diffusion simulations could help to identify key feedforward and feedback regulatory motifs regulating the switch between an LTP and an LTD signaling module in SP/SA-containing Spines, thus helping to find a unified view of SP/SA action in Hebbian plasticity.
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impairment of in vivo theta burst long term potentiation and network excitability in the dentate gyrus of synaptopodin deficient mice lacking the Spine Apparatus and the cisternal organelle
Hippocampus, 2009Co-Authors: Peter Jedlicka, Stephan W Schwarzacher, Carlos Bas Orth, Michael Frotscher, Raphael Winkels, Friederike Kienzler, Clive R Bramham, Christian Schultz, Thomas DellerAbstract:The function of the Spine Apparatus in dendritic Spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin 2/2 mice. Here, we used synaptopodin 2/2 mice to explore the role of the Spine appa- ratus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation follow- ing theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the Spine Apparatus and the cisternal organelle leads to a defect in long- term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. V C 2008 Wiley-Liss, Inc.
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a role for the Spine Apparatus in ltp and spatial learning
Behavioural Brain Research, 2008Co-Authors: Peter Jedlicka, Andreas Vlachos, Stephan W Schwarzacher, Thomas DellerAbstract:Long-term potentiation (LTP) of synaptic strength is a long-lasting form of synaptic plasticity that has been linked to information storage. Although the molecular and cellular events underlying LTP are not yet fully understood, it is generally accepted that changes in dendritic Spine calcium levels as well as local protein synthesis play a central role. These two processes may be influenced by the presence of a Spine Apparatus, a distinct neuronal organelle found in a subpopulation of telencephalic Spines. Mice lacking Spine Apparatuses (synaptopodin-deficient mice) show deficits in LTP and impaired spatial learning supporting the involvement of the Spine Apparatus in synaptic plasticity. In our review, we consider the possible roles of the Spine Apparatus in LTP1 (protein synthesis-independent), LTP2 (translation-dependent and transcription-independent) and LTP3 (translation- and transcription-dependent) and discuss the effects of the Spine Apparatus on learning and memory.
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a role for synaptopodin and the Spine Apparatus in hippocampal synaptic plasticity
Annals of Anatomy-anatomischer Anzeiger, 2007Co-Authors: Thomas Deller, Andreas Vlachos, Martin Korte, Sophie Chabanis, Alexander Drakew, Herbert Schwegler, Carlos Bas Orth, Domenico Del Turco, Guido J Burbach, Carola A HaasAbstract:Spines are considered sites of synaptic plasticity in the brain and are capable of remodeling their shape and size. A molecule thathas been implicated in Spine plasticity is the actin-associated protein synaptopodin. This article will review a series of studies aimed at elucidating the role of synaptopodin in the rodent brain. First, the developmental expression of synaptopodin mRNA and protein were studied; secondly, the subcellular localization of synaptopodin in hippocampal principal neurons was analyzed using confocal microscopy as well as electron microscopy and immunogold labelling; and, finally, the functional role of synaptopodin was investigated using a synaptopodin-deficient mouse. The results of these studies are: (1) synaptopodin expression byhippocampal principal neurons develops during the first postnatal weeks and increases in parallel with the maturation of Spines in the hippocampus. (2) Synaptopodin is sorted to the Spine compartment, where it is tightly associated with the Spine Apparatus, an enigmatic organelle believed to be involved in calcium storage or local protein synthesis. (3) Synaptopodin-deficient mice generated by gene targeting are viable but lack the Spine Apparatus organelle. These mice show deficitsin synaptic plasticity as well as impaired learning and memory. Taken together, these data implicate synaptopodin and the Spine Apparatus in the regulation of synaptic plasticity in the hippocampus. Future studies will be aimed at finding the molecular link between synaptopodin, the Spine Apparatus organelle, and synaptic plasticity.
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lamina specific distribution of synaptopodin an actin associated molecule essential for the Spine Apparatus in identified principal cell dendrites of the mouse hippocampus
The Journal of Comparative Neurology, 2005Co-Authors: Carlos Bas Orth, Andreas Vlachos, Domenico Del Turco, Guido J Burbach, Carola A Haas, Peter Mundel, Michael Frotscher, Guoping Feng, Thomas DellerAbstract:Synaptopodin is an actin-associated molecule found in a subset of telencephalic Spines. It is an essential component of the Spine Apparatus, a Ca(2+)-storing organelle and has been implicated in synaptic plasticity (Deller et al. [2003] Proc Natl Acad Sci U S A 100:10494-10499). In the rodent hippocampus, Synaptopodin is distributed in a characteristic region- and lamina-specific manner. To learn more about the cellular basis underlying this distribution, the regional, laminar, and cellular localization of Synaptopodin and its mRNA were analyzed in mouse hippocampus. First, Synaptopodin puncta densities were quantified after immunofluorescent labeling using confocal microscopy. Second, the dendritic distribution of Synaptopodin-positive puncta was studied using three-dimensional confocal reconstructions of Synaptopodin-immunostained and enhanced green fluorescence protein (EGFP)-labeled principal neurons. Synaptopodin puncta located within dendrites of principal neurons were primarily found in Spines (>95%). Analysis of dendritic segments located in different layers revealed lamina-specific differences in the percentage of Synaptopodin-positive Spines. Densities ranged between 37% (outer molecular layer) and 14% (stratum oriens; CA1). Finally, synaptopodin mRNA expression was studied using in situ hybridization, laser microdissection, and quantitative reverse transcriptase-polymerase chain reaction. Expression levels were comparable between all regions. These data demonstrate a lamina-specific distribution of Synaptopodin within dendritic segments of identified neurons. Within dendrites, the majority of Synaptopodin-positive puncta were located in Spines where they represent Spine Apparatuses. We conclude, that this organelle is distributed in a region- and layer-specific manner in the mouse hippocampus and suggest that differences in the activity of afferent fiber systems could determine its distribution.
Michael Frotscher - One of the best experts on this subject based on the ideXlab platform.
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myosin v regulates synaptopodin clustering and localization in the dendrites of hippocampal neurons
Journal of Cell Science, 2019Co-Authors: Anja Konietzny, Alexander Drakew, Michael Frotscher, Judit Gonzalezgallego, Alberto Perezalvarez, Jeroen Demmers, Dick H W Dekkers, John A Hammer, Thomas G Oertner, Wolfgang WagnerAbstract:The Spine Apparatus (SA) is an endoplasmic reticulum-related organelle which is present in a subset of dendritic Spines in cortical and pyramidal neurons, and plays an important role in calcium homeostasis and dendritic Spine plasticity. The protein synaptopodin is essential for the formation of the SA and is widely used as a maker for this organelle. However, it is still unclear which factors contribute to its localization at selected synapses, and how it triggers local SA formation. In this study we characterized development, localization and mobility of synaptopodin clusters in hippocampal primary neurons, as well as the molecular dynamics within these clusters. Interestingly, synaptopodin at the shaft-associated clusters is less dynamic than at spinous clusters. We identify the actin-based motor proteins myosin V and VI as novel interaction partners of synaptopodin and demonstrate that myosin V is important for the formation and/or maintenance of the SA. We found no evidence of active microtubule-based transport of synaptopodin. Instead, new clusters emerge inside Spines, which we interpret as the SA being assembled on-site.
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impairment of in vivo theta burst long term potentiation and network excitability in the dentate gyrus of synaptopodin deficient mice lacking the Spine Apparatus and the cisternal organelle
Hippocampus, 2009Co-Authors: Peter Jedlicka, Stephan W Schwarzacher, Carlos Bas Orth, Michael Frotscher, Raphael Winkels, Friederike Kienzler, Clive R Bramham, Christian Schultz, Thomas DellerAbstract:The function of the Spine Apparatus in dendritic Spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin 2/2 mice. Here, we used synaptopodin 2/2 mice to explore the role of the Spine appa- ratus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation follow- ing theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the Spine Apparatus and the cisternal organelle leads to a defect in long- term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. V C 2008 Wiley-Liss, Inc.
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lamina specific distribution of synaptopodin an actin associated molecule essential for the Spine Apparatus in identified principal cell dendrites of the mouse hippocampus
The Journal of Comparative Neurology, 2005Co-Authors: Carlos Bas Orth, Andreas Vlachos, Domenico Del Turco, Guido J Burbach, Carola A Haas, Peter Mundel, Michael Frotscher, Guoping Feng, Thomas DellerAbstract:Synaptopodin is an actin-associated molecule found in a subset of telencephalic Spines. It is an essential component of the Spine Apparatus, a Ca(2+)-storing organelle and has been implicated in synaptic plasticity (Deller et al. [2003] Proc Natl Acad Sci U S A 100:10494-10499). In the rodent hippocampus, Synaptopodin is distributed in a characteristic region- and lamina-specific manner. To learn more about the cellular basis underlying this distribution, the regional, laminar, and cellular localization of Synaptopodin and its mRNA were analyzed in mouse hippocampus. First, Synaptopodin puncta densities were quantified after immunofluorescent labeling using confocal microscopy. Second, the dendritic distribution of Synaptopodin-positive puncta was studied using three-dimensional confocal reconstructions of Synaptopodin-immunostained and enhanced green fluorescence protein (EGFP)-labeled principal neurons. Synaptopodin puncta located within dendrites of principal neurons were primarily found in Spines (>95%). Analysis of dendritic segments located in different layers revealed lamina-specific differences in the percentage of Synaptopodin-positive Spines. Densities ranged between 37% (outer molecular layer) and 14% (stratum oriens; CA1). Finally, synaptopodin mRNA expression was studied using in situ hybridization, laser microdissection, and quantitative reverse transcriptase-polymerase chain reaction. Expression levels were comparable between all regions. These data demonstrate a lamina-specific distribution of Synaptopodin within dendritic segments of identified neurons. Within dendrites, the majority of Synaptopodin-positive puncta were located in Spines where they represent Spine Apparatuses. We conclude, that this organelle is distributed in a region- and layer-specific manner in the mouse hippocampus and suggest that differences in the activity of afferent fiber systems could determine its distribution.
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synaptopodin a molecule involved in the formation of the dendritic Spine Apparatus is a dual actin alpha actinin binding protein
Journal of Neurochemistry, 2005Co-Authors: Joachim Kremerskothen, Michael Frotscher, Christian Plaas, Stefan Kindler, Angelika BarnekowAbstract:Synaptopodin (SYNPO) is a cytoskeletal protein that is preferentially located in mature dendritic Spines, where it accumulates in the Spine neck and closely associates with the Spine Apparatus. Formation of the Spine Apparatus critically depends on SYNPO. To further determine its molecular action, we screened for cellular binding partners. Using the yeast two-hybrid system and biochemical assays, SYNPO was found to associate with both F-actin and α-actinin. Ectopic expression of SYNPO in neuronal and non-neuronal cells induced actin aggregates, thus confirming a cytoplasmic interaction with the actin cytoskeleton. Whereas F-actin association is mediated by a central SYNPO motif, binding to α-actinin requires the C-terminal domain. Notably, the α-actinin binding domain is also essential for dendritic targeting and postsynaptic accumulation of SYNPO in primary neurons. Taken together, our data suggest that dendritic Spine accumulation of SYNPO critically depends on its interaction with postsynaptic α-actinin and that SYNPO may regulate Spine morphology, motility and function via its distinct modes of association with the actin cytoskeleton.
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actin associated protein synaptopodin in the rat hippocampal formation localization in the Spine neck and close association with the Spine Apparatus of principal neurons
The Journal of Comparative Neurology, 2000Co-Authors: T Deller, Tobias Merten, Stephanie U Roth, Peter Mundel, Michael FrotscherAbstract:Dendritic Spines are sites of synaptic plasticity in the brain and are capable of remodeling their shape and size. However, little is known about the cellular mechanisms that regulate Spine morphology and motility. Synaptopodin is a recently described actin-associated protein found in renal podocytes and dendritic Spines (Mundel et al. J Cell Biol. [1997] 139:193–204), which is believed to play a role in Spine plasticity. The presentstudy analyzed the distribution of synaptopodin in the hippocampal formation. In situ hybridization histochemistry revealed a high constitutive expression of synaptopodin mRNA in the principal cell layers. Light microscopic immunohistochemistry showed that the protein is distributed throughout the hippocampal formation in a region- and lamina-specific manner. Postembedding immunogold histochemistry demonstrated that synaptopodin is exclusively present in dendrites and Spines, specifically in the Spine neck in close association with the Spine Apparatus. Spines lacking a Spine Apparatus are not immunoreactive for synaptopodin. These data suggest that synaptopodin links the Spine Apparatus to actin and may thus be involved in the actin-based plasticity of Spines. J. Comp. Neurol. 418:164–181, 2000. © 2000 Wiley-Liss, Inc.
Peter Jedlicka - One of the best experts on this subject based on the ideXlab platform.
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understanding the role of synaptopodin and the Spine Apparatus in hebbian synaptic plasticity new perspectives and the need for computational modeling
Neurobiology of Learning and Memory, 2017Co-Authors: Peter Jedlicka, Thomas DellerAbstract:Synaptopodin (SP) is a proline-rich actin-associated protein essential for the formation of a Spine Apparatus (SA) in dendritic Spines. The SA consists of stacks of smooth endoplasmic reticulum (sER) contiguous with the meshwork of somatodendritic ER. Spines of SP-deficient mice contain sER but no SA, demonstrating that SP is necessary for the assembly of ER cisterns into the more complex SA organelle. Although the SA was described decades ago, its function was difficult to investigate and remained elusive, in part because reliable markers for the SA were missing. After SP was identified as an essential component and a reliable marker of the SA, a role of SP/SA in hippocampal synaptic plasticity could be firmly established using loss-of-function approaches. Further studies revealed that SP/SA participate in the regulation of Ca2+-dependent Spine-specific Hebbian plasticity and in activity-dependent changes in the Spine actin cytoskeleton. In this review we are summarizing recent progress made on SP/SA in Hebbian plasticity and discuss open questions such as causality, spatiotemporal dynamics and complementarity of SP/SA-dependent mechanisms. We are proposing that computational modeling of Spine Ca2+-signaling and actin remodeling pathways could address some of these issues and could indicate future research directions. Moreover, reaction-diffusion simulations could help to identify key feedforward and feedback regulatory motifs regulating the switch between an LTP and an LTD signaling module in SP/SA-containing Spines, thus helping to find a unified view of SP/SA action in Hebbian plasticity.
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impairment of in vivo theta burst long term potentiation and network excitability in the dentate gyrus of synaptopodin deficient mice lacking the Spine Apparatus and the cisternal organelle
Hippocampus, 2009Co-Authors: Peter Jedlicka, Stephan W Schwarzacher, Carlos Bas Orth, Michael Frotscher, Raphael Winkels, Friederike Kienzler, Clive R Bramham, Christian Schultz, Thomas DellerAbstract:The function of the Spine Apparatus in dendritic Spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin 2/2 mice. Here, we used synaptopodin 2/2 mice to explore the role of the Spine appa- ratus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation follow- ing theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the Spine Apparatus and the cisternal organelle leads to a defect in long- term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. V C 2008 Wiley-Liss, Inc.
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a role for the Spine Apparatus in ltp and spatial learning
Behavioural Brain Research, 2008Co-Authors: Peter Jedlicka, Andreas Vlachos, Stephan W Schwarzacher, Thomas DellerAbstract:Long-term potentiation (LTP) of synaptic strength is a long-lasting form of synaptic plasticity that has been linked to information storage. Although the molecular and cellular events underlying LTP are not yet fully understood, it is generally accepted that changes in dendritic Spine calcium levels as well as local protein synthesis play a central role. These two processes may be influenced by the presence of a Spine Apparatus, a distinct neuronal organelle found in a subpopulation of telencephalic Spines. Mice lacking Spine Apparatuses (synaptopodin-deficient mice) show deficits in LTP and impaired spatial learning supporting the involvement of the Spine Apparatus in synaptic plasticity. In our review, we consider the possible roles of the Spine Apparatus in LTP1 (protein synthesis-independent), LTP2 (translation-dependent and transcription-independent) and LTP3 (translation- and transcription-dependent) and discuss the effects of the Spine Apparatus on learning and memory.
Andreas Vlachos - One of the best experts on this subject based on the ideXlab platform.
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the Spine Apparatus synaptopodin and dendritic Spine plasticity
The Neuroscientist, 2010Co-Authors: Menahem Segal, Andreas Vlachos, Eduard KorkotianAbstract:The Spine Apparatus (SA) is an essential component of mature dendritic Spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, colocalizes with the SA. Hippocampal neurons in SP-knockout mice lack SA, and they express lower LTP. SP probably plays a role in synaptic plasticity, but only recently it is being linked mechanistically to synaptic functions. These authors and others have studied endogenous and transfected SP in dendritic Spines of cultured hippocampal neurons. They found that Spines containing SP generate twice as large responses to flash photolysis of caged glutamate than SP-negative ones. An N-methyl-d-aspartate receptor—mediated chemical LTP caused accumulation of GFP-GluR1 in Spine heads of control but not of shRNA transfected, SP-deficient neurons. SP is linked to calcium stores, because their pharmacological blockade eliminated SP-related enhancement of glutamate responses. Furthermore, release of calcium from stores p...
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a role for the Spine Apparatus in ltp and spatial learning
Behavioural Brain Research, 2008Co-Authors: Peter Jedlicka, Andreas Vlachos, Stephan W Schwarzacher, Thomas DellerAbstract:Long-term potentiation (LTP) of synaptic strength is a long-lasting form of synaptic plasticity that has been linked to information storage. Although the molecular and cellular events underlying LTP are not yet fully understood, it is generally accepted that changes in dendritic Spine calcium levels as well as local protein synthesis play a central role. These two processes may be influenced by the presence of a Spine Apparatus, a distinct neuronal organelle found in a subpopulation of telencephalic Spines. Mice lacking Spine Apparatuses (synaptopodin-deficient mice) show deficits in LTP and impaired spatial learning supporting the involvement of the Spine Apparatus in synaptic plasticity. In our review, we consider the possible roles of the Spine Apparatus in LTP1 (protein synthesis-independent), LTP2 (translation-dependent and transcription-independent) and LTP3 (translation- and transcription-dependent) and discuss the effects of the Spine Apparatus on learning and memory.
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a role for synaptopodin and the Spine Apparatus in hippocampal synaptic plasticity
Annals of Anatomy-anatomischer Anzeiger, 2007Co-Authors: Thomas Deller, Andreas Vlachos, Martin Korte, Sophie Chabanis, Alexander Drakew, Herbert Schwegler, Carlos Bas Orth, Domenico Del Turco, Guido J Burbach, Carola A HaasAbstract:Spines are considered sites of synaptic plasticity in the brain and are capable of remodeling their shape and size. A molecule thathas been implicated in Spine plasticity is the actin-associated protein synaptopodin. This article will review a series of studies aimed at elucidating the role of synaptopodin in the rodent brain. First, the developmental expression of synaptopodin mRNA and protein were studied; secondly, the subcellular localization of synaptopodin in hippocampal principal neurons was analyzed using confocal microscopy as well as electron microscopy and immunogold labelling; and, finally, the functional role of synaptopodin was investigated using a synaptopodin-deficient mouse. The results of these studies are: (1) synaptopodin expression byhippocampal principal neurons develops during the first postnatal weeks and increases in parallel with the maturation of Spines in the hippocampus. (2) Synaptopodin is sorted to the Spine compartment, where it is tightly associated with the Spine Apparatus, an enigmatic organelle believed to be involved in calcium storage or local protein synthesis. (3) Synaptopodin-deficient mice generated by gene targeting are viable but lack the Spine Apparatus organelle. These mice show deficitsin synaptic plasticity as well as impaired learning and memory. Taken together, these data implicate synaptopodin and the Spine Apparatus in the regulation of synaptic plasticity in the hippocampus. Future studies will be aimed at finding the molecular link between synaptopodin, the Spine Apparatus organelle, and synaptic plasticity.
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lamina specific distribution of synaptopodin an actin associated molecule essential for the Spine Apparatus in identified principal cell dendrites of the mouse hippocampus
The Journal of Comparative Neurology, 2005Co-Authors: Carlos Bas Orth, Andreas Vlachos, Domenico Del Turco, Guido J Burbach, Carola A Haas, Peter Mundel, Michael Frotscher, Guoping Feng, Thomas DellerAbstract:Synaptopodin is an actin-associated molecule found in a subset of telencephalic Spines. It is an essential component of the Spine Apparatus, a Ca(2+)-storing organelle and has been implicated in synaptic plasticity (Deller et al. [2003] Proc Natl Acad Sci U S A 100:10494-10499). In the rodent hippocampus, Synaptopodin is distributed in a characteristic region- and lamina-specific manner. To learn more about the cellular basis underlying this distribution, the regional, laminar, and cellular localization of Synaptopodin and its mRNA were analyzed in mouse hippocampus. First, Synaptopodin puncta densities were quantified after immunofluorescent labeling using confocal microscopy. Second, the dendritic distribution of Synaptopodin-positive puncta was studied using three-dimensional confocal reconstructions of Synaptopodin-immunostained and enhanced green fluorescence protein (EGFP)-labeled principal neurons. Synaptopodin puncta located within dendrites of principal neurons were primarily found in Spines (>95%). Analysis of dendritic segments located in different layers revealed lamina-specific differences in the percentage of Synaptopodin-positive Spines. Densities ranged between 37% (outer molecular layer) and 14% (stratum oriens; CA1). Finally, synaptopodin mRNA expression was studied using in situ hybridization, laser microdissection, and quantitative reverse transcriptase-polymerase chain reaction. Expression levels were comparable between all regions. These data demonstrate a lamina-specific distribution of Synaptopodin within dendritic segments of identified neurons. Within dendrites, the majority of Synaptopodin-positive puncta were located in Spines where they represent Spine Apparatuses. We conclude, that this organelle is distributed in a region- and layer-specific manner in the mouse hippocampus and suggest that differences in the activity of afferent fiber systems could determine its distribution.
Carlos Bas Orth - One of the best experts on this subject based on the ideXlab platform.
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impairment of in vivo theta burst long term potentiation and network excitability in the dentate gyrus of synaptopodin deficient mice lacking the Spine Apparatus and the cisternal organelle
Hippocampus, 2009Co-Authors: Peter Jedlicka, Stephan W Schwarzacher, Carlos Bas Orth, Michael Frotscher, Raphael Winkels, Friederike Kienzler, Clive R Bramham, Christian Schultz, Thomas DellerAbstract:The function of the Spine Apparatus in dendritic Spines and the cisternal organelles in axon initial segments is little understood. The actin-associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin 2/2 mice. Here, we used synaptopodin 2/2 mice to explore the role of the Spine appa- ratus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long-term potentiation follow- ing theta-burst stimulation, whereas tetanus-evoked LTP was unaffected. Furthermore, paired-pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the Spine Apparatus and the cisternal organelle leads to a defect in long- term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. V C 2008 Wiley-Liss, Inc.
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a role for synaptopodin and the Spine Apparatus in hippocampal synaptic plasticity
Annals of Anatomy-anatomischer Anzeiger, 2007Co-Authors: Thomas Deller, Andreas Vlachos, Martin Korte, Sophie Chabanis, Alexander Drakew, Herbert Schwegler, Carlos Bas Orth, Domenico Del Turco, Guido J Burbach, Carola A HaasAbstract:Spines are considered sites of synaptic plasticity in the brain and are capable of remodeling their shape and size. A molecule thathas been implicated in Spine plasticity is the actin-associated protein synaptopodin. This article will review a series of studies aimed at elucidating the role of synaptopodin in the rodent brain. First, the developmental expression of synaptopodin mRNA and protein were studied; secondly, the subcellular localization of synaptopodin in hippocampal principal neurons was analyzed using confocal microscopy as well as electron microscopy and immunogold labelling; and, finally, the functional role of synaptopodin was investigated using a synaptopodin-deficient mouse. The results of these studies are: (1) synaptopodin expression byhippocampal principal neurons develops during the first postnatal weeks and increases in parallel with the maturation of Spines in the hippocampus. (2) Synaptopodin is sorted to the Spine compartment, where it is tightly associated with the Spine Apparatus, an enigmatic organelle believed to be involved in calcium storage or local protein synthesis. (3) Synaptopodin-deficient mice generated by gene targeting are viable but lack the Spine Apparatus organelle. These mice show deficitsin synaptic plasticity as well as impaired learning and memory. Taken together, these data implicate synaptopodin and the Spine Apparatus in the regulation of synaptic plasticity in the hippocampus. Future studies will be aimed at finding the molecular link between synaptopodin, the Spine Apparatus organelle, and synaptic plasticity.
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lamina specific distribution of synaptopodin an actin associated molecule essential for the Spine Apparatus in identified principal cell dendrites of the mouse hippocampus
The Journal of Comparative Neurology, 2005Co-Authors: Carlos Bas Orth, Andreas Vlachos, Domenico Del Turco, Guido J Burbach, Carola A Haas, Peter Mundel, Michael Frotscher, Guoping Feng, Thomas DellerAbstract:Synaptopodin is an actin-associated molecule found in a subset of telencephalic Spines. It is an essential component of the Spine Apparatus, a Ca(2+)-storing organelle and has been implicated in synaptic plasticity (Deller et al. [2003] Proc Natl Acad Sci U S A 100:10494-10499). In the rodent hippocampus, Synaptopodin is distributed in a characteristic region- and lamina-specific manner. To learn more about the cellular basis underlying this distribution, the regional, laminar, and cellular localization of Synaptopodin and its mRNA were analyzed in mouse hippocampus. First, Synaptopodin puncta densities were quantified after immunofluorescent labeling using confocal microscopy. Second, the dendritic distribution of Synaptopodin-positive puncta was studied using three-dimensional confocal reconstructions of Synaptopodin-immunostained and enhanced green fluorescence protein (EGFP)-labeled principal neurons. Synaptopodin puncta located within dendrites of principal neurons were primarily found in Spines (>95%). Analysis of dendritic segments located in different layers revealed lamina-specific differences in the percentage of Synaptopodin-positive Spines. Densities ranged between 37% (outer molecular layer) and 14% (stratum oriens; CA1). Finally, synaptopodin mRNA expression was studied using in situ hybridization, laser microdissection, and quantitative reverse transcriptase-polymerase chain reaction. Expression levels were comparable between all regions. These data demonstrate a lamina-specific distribution of Synaptopodin within dendritic segments of identified neurons. Within dendrites, the majority of Synaptopodin-positive puncta were located in Spines where they represent Spine Apparatuses. We conclude, that this organelle is distributed in a region- and layer-specific manner in the mouse hippocampus and suggest that differences in the activity of afferent fiber systems could determine its distribution.