Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron Excitability In vitro and Spatial Working Memory In vivo

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Date
2016-11-07
Authors
Weth-Malsch, Daniela
Langeslag, Michiel
Beroukas, Dimitra
Zangrandi, Luca
Kastenberger, Iris
Quarta, Serena
Malsch, Philipp
Kalpachidou, Theodora
Schwarzer, Christoph
Proia, Richard L
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Publisher
Frontiers Media S.A.
Rights
© 2016 Weth-Malsch, Langeslag, Beroukas, Zangrandi, Kastenberger, Quarta, Malsch, Kalpachidou, Schwarzer, Proia, Haberberger and Kress.
Rights Holder
Weth-Malsch, Langeslag, Beroukas, Zangrandi, Kastenberger, Quarta, Malsch, Kalpachidou, Schwarzer, Proia, Haberberger and Kress.
Abstract
Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3) in vivo and in vitro with a special focus on the hippocampus. Using an S1P3 knock-out mouse model we applied a range of behavioral tests, performed expression studies, and whole cell patch clamp recordings in acute hippocampal slices. We were able to show that S1P3 deficient mice display a significant spatial working memory deficit within the T-maze test, but not in anxiety related tests. Furthermore, S1p3 mRNA was expressed throughout the hippocampal formation. Principal neurons in area CA3 lacking S1P3 showed significantly increased interspike intervals and a significantly decreased input resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype and S1P−/−3 mice displayed significantly increased evoked EPSC amplitudes and decay times, whereas rise times remained unchanged. These results suggest a specific involvement of S1P3 for the establishment of spatial working memory and neuronal excitability within the hippocampus.
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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords
sphingosine 1-phosphate, S1P receptor 3, hippocampus, working memory, neuron excitability
Citation
Weth-Malsch D, Langeslag M, Beroukas D, Zangrandi L, Kastenberger I, Quarta S, Malsch P, Kalpachidou T, Schwarzer C, Proia RL, Haberberger RV and Kress M (2016) Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron Excitability In vitro and Spatial Working Memory In vivo. Front. Cell. Neurosci. 10:258. doi: 10.3389/fncel.2016.00258