title: Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron ExcitabilityIn vitroand Spatial Working MemoryIn vivo.
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 vivoandin vitrowith a special focus on the hippocampus. Using an S1P3knock-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 S1P3deficient mice display a significant spatial working memory deficit within the T-maze test, but not in anxiety related tests. Furthermore,S1p3mRNA was expressed throughout the hippocampal formation. Principal neurons in area CA3 lacking S1P3showed significantly increased interspike intervals and a significantly decreased input resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype and [Formula: see text] mice displayed significantly increased evoked EPSC amplitudes and decay times, whereas rise times remained unchanged. These results suggest a specific involvement of S1P3for the establishment of spatial working memory and neuronal excitability within the hippocampus.
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weth-Malsch
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Michiel
authors.initials: M
authors.lastname: Langeslag
authors.affiliation: Anatomy and Histology and Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Beroukas
authors.affiliation: Department of Pharmacology, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Luca
authors.initials: L
authors.lastname: Zangrandi
authors.affiliation: Department of Pharmacology, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Iris
authors.initials: I
authors.lastname: Kastenberger
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Serena
authors.initials: S
authors.lastname: Quarta
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Malsch
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Theodora
authors.initials: T
authors.lastname: Kalpachidou
authors.affiliation: Department of Pharmacology, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwarzer
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases Bethesda, MD, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.affiliation: Anatomy and Histology and Centre for Neuroscience, Flinders University Adelaide, SA, Australia.
authors.forename: Rainer V
authors.initials: RV
authors.lastname: Haberberger
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck Innsbruck, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kress
keywords: S1P receptor 3; hippocampus; neuron excitability; sphingosine 1-phosphate; working memory