Constitutive tumor necrosis factor (TNF)-deficiency causes a reduction in spine density in mouse dentate granule cells accompanied by homeostatic adaptations of spine head size

  • The majority of excitatory synapses terminating on cortical neurons are found on dendritic spines. The geometry of spines, in particular the size of the spine head, tightly correlates with the strength of the excitatory synapse formed with the spine. Under conditions of synaptic plasticity, spine geometry may change, reflecting functional adaptations. Since the cytokine tumor necrosis factor (TNF) has been shown to influence synaptic transmission as well as Hebbian and homeostatic forms of synaptic plasticity, we speculated that TNF-deficiency may cause concomitant structural changes at the level of dendritic spines. To address this question, we analyzed spine density and spine head area of Alexa568-filled granule cells in the dentate gyrus of adult C57BL/6J and TNF-deficient (TNF-KO) mice. Tissue sections were double-stained for the actin-modulating and plasticity-related protein synaptopodin (SP), a molecular marker for strong and stable spines. Dendritic segments of TNF-deficient granule cells exhibited ∼20% fewer spines in the outer molecular layer of the dentate gyrus compared to controls, indicating a reduced afferent innervation. Of note, these segments also had larger spines containing larger SP-clusters. This pattern of changes is strikingly similar to the one seen after denervation-associated spine loss following experimental entorhinal denervation of granule cells: Denervated granule cells increase the SP-content and strength of their remaining spines to homeostatically compensate for those that were lost. Our data suggest a similar compensatory mechanism in TNF-deficient granule cells in response to a reduction in their afferent innervation.
Author:Dinko Smilovic, Michael Rietsche, Alexander Drakew, Mario Vuksic, Thomas DellerORCiDGND
Parent Title (English):The journal of comparative neurology
Place of publication:New York, NY [u.a.]
Document Type:Article
Date of Publication (online):2021/09/09
Date of first Publication:2021/09/09
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/04/04
Tag:dentate gyrus; homeostatic plasticity; spine head; synaptic plasticity; synaptopodin; tumor necrosis factor
Page Number:14
First Page:656
Last Page:669
This work was supported by the bilateral Croatian-German project (Ministry of Science and Education of the Republic of Croatia and Deutscher Akademischer Austauschdienst (MZOŠ-DAAD) to M.V. and T.D.), Deutsche Forschungsgemeinschaft (DFG CRC 1080 to T.D.), the Scientific Centre of Excellence for Basic, Clinical and Translation Neuroscience (project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain“; GA KK01. funded by the European Union through the European Regional Development Fund), Europass Mobility grant (to D.S.) and Dr. Senckenbergische Stiftung (to T.D.).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0