Abstract
Synaptopodin (SP) is localized within the spine apparatus, an enigmatic structure located in the neck of spines of central excitatory neurons. It serves as a link between the spine head, where the synapse is located, and the endoplasmic reticulum (ER) in the parent dendrite. SP is also located in the axon initial segment, in association with the cisternal organelle, another structure related to the endoplasmic reticulum. Extensive research using SP knockout (SPKO) mice suggest that SP has a pivotal role in structural and functional plasticity. Consequently, young adult SPKO mice were shown to be deficient in cognitive functions, and in ability to undergo long-term potentiation of reactivity to afferent stimulation. However, although SP expresses differently during maturation, its role in synaptic and intrinsic neuronal mechanisms in adult SPKO mice is still unclear. To address this knowledge gap we analyzed hippocampus bulk mRNA in SPKO mice, and we recorded the activity of CA1 neurons in the mouse hippocampus slice, with both extracellular and patch recording methods. Electrophysiologically, SPKO cells in CA1 region of the dorsal hippocampus were more excitable than wild type (wt) ones. In addition, exposure of mice to a complex environment caused a higher proportion of arc-expressing cells in SPKO than in wt mice hippocampus. These experiments indicate that higher excitability and higher expression of arc staining may reflect SP deficiency in the hippocampus of adult SPKO mice.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank Drs. R. Eilam and S. Haidarliu for help with the immunohistochemical analysis.
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Supported by a grant from the Clore Center for Biological Physics of the Weizmann Institute of Science.
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EA conducted the RNAseq analysis, and the extracellular electrophysiological experiments, and wrote the manuscript. SV conducted and analyzed the patch recording experiments, LK conducted the behavioral and immunohistochemical studies, EK and MS wrote the manuscript. All co-authors have read and commented on the manuscript and agreed to have their names listed as authors.
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Experiments were conducted by the rules of the Institutional Animal Care and use Committee, approval number: 38390917-2.
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Aloni, E., Verbitsky, S., Kushnireva, L. et al. Increased excitability of hippocampal neurons in mature synaptopodin-knockout mice. Brain Struct Funct 226, 2459–2466 (2021). https://doi.org/10.1007/s00429-021-02346-0
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DOI: https://doi.org/10.1007/s00429-021-02346-0