title: Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.
abstract: Altered synaptic bioactive lipid signaling has been recently shown to augment neuronal excitation in the hippocampus of adult animals by activation of presynaptic LPA2-receptors leading to increased presynaptic glutamate release. Here, we show that this results in higher postsynaptic Ca2+ levels and in premature onset of spontaneous neuronal activity in the developing entorhinal cortex. Interestingly, increased synchronized neuronal activity led to reduced axon growth velocity of entorhinal neurons which project via the perforant path to the hippocampus. This was due to Ca2+-dependent molecular signaling to the axon affecting stabilization of the actin cytoskeleton. The spontaneous activity affected the entire entorhinal cortical network and thus led to reduced overall axon fiber numbers in the mature perforant path that is known to be important for specific memory functions. Our data show that precise regulation of early cortical activity by bioactive lipids is of critical importance for proper circuit formation.
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogt
authors.affiliation: Institute of Physiology, University Medical Center, Johannes Gutenberg-University, 55128 Mainz, Germany.
authors.forename: Sergei
authors.initials: S
authors.lastname: Kirischuk
authors.affiliation: Institute of Physiology, University Medical Center, Johannes Gutenberg-University, 55128 Mainz, Germany.
authors.forename: Petr
authors.initials: P
authors.lastname: Unichenko
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Leslie
authors.initials: L
authors.lastname: Schlüter
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Assunta
authors.initials: A
authors.lastname: Pelosi
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Endle
authors.affiliation: Institute of Physiology, University Medical Center, Johannes Gutenberg-University, 55128 Mainz, Germany.
authors.forename: Jenq-Wei
authors.initials: JW
authors.lastname: Yang
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Schmarowski
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Jin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Carine
authors.initials: C
authors.lastname: Thalman
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin, 10119 Berlin, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Strauss
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Prokudin
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: B Suman
authors.initials: BS
authors.lastname: Bharati
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.affiliation: Institute of Physiological Chemistry, University Medical Center, Johannes Gutenberg-University, 55128 Mainz, Germany.
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Institute of Physiology, University Medical Center, Johannes Gutenberg-University, 55128 Mainz, Germany.
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
authors.affiliation: Institute for Microscopic Anatomy and Neurobiology, University Medical Center, Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D051379:Mice; D000071446:Neuronal Outgrowth / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D010743:Phospholipids; D018698:Glutamic Acid; D002118:Calcium
keywords: Ca2+-signaling; axon outgrowth; bioactive phospholipids; early synchronized activity; entorhinal–hippocampal formation