title: Synaptopodin regulates denervation-induced homeostatic synaptic plasticity.
abstract: Synaptopodin (SP) is a marker and essential component of the spine apparatus (SA), an enigmatic cellular organelle composed of stacked smooth endoplasmic reticulum that has been linked to synaptic plasticity. However, SP/SA-mediated synaptic plasticity remains incompletely understood. To study the role of SP/SA in homeostatic synaptic plasticity we here used denervation-induced synaptic scaling of mouse dentate granule cells as a model system. This form of plasticity is of considerable interest in the context of neurological diseases that are associated with the loss of neurons and subsequent denervation of connected brain regions. In entorhino-hippocampal slice cultures prepared from SP-deficient mice, which lack the SA, a compensatory increase in excitatory synaptic strength was not observed following partial deafferentation. In line with this finding, prolonged blockade of sodium channels with tetrodotoxin induced homeostatic synaptic scaling in wild-type, but not SP-deficient, slice cultures. By crossing SP-deficient mice with a newly generated transgenic mouse strain that expresses GFP-tagged SP under the control of the Thy1.2 promoter, the ability of dentate granule cells to form the SA and to homeostatically strengthen excitatory synapses was rescued. Interestingly, homeostatic synaptic strengthening was accompanied by a compensatory increase in SP cluster size/stability and SA stack number, suggesting that activity-dependent SP/SA remodeling could be part of a negative feedback mechanism that aims at adjusting the strength of excitatory synapses to persisting changes in network activity. Thus, our results disclose an important role for SP/SA in homeostatic synaptic plasticity.
authors: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, 60590 Frankfurt, Germany. a.vlachos@med.uni-frankfurt.de
authors: Andreas
authors: A
authors: Vlachos
authors: Benno
authors: B
authors: Ikenberg
authors: Maximilian
authors: M
authors: Lenz
authors: Denise
authors: D
authors: Becker
authors: Kurt
authors: K
authors: Reifenberg
authors: Carlos
authors: C
authors: Bas-Orth
authors: Thomas
authors: T
authors: Deller
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D003714:Denervation; D018891:Dentate Gyrus / Q000166:cytology*; D018728:Entorhinal Cortex / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006706:Homeostasis; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D011401:Promoter Regions, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D008840:Microfilament Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; C503968:Synpo protein, mouse; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin
keywords: NMDA receptors; entorhinal cortex lesion; intracellular calcium stores; ryanodine receptors; voltage-gated calcium channels
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