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RESEARCH PRODUCT
Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.
Nikolai SchmarowskiPetr UnichenkoJerold ChunSergei KirischukBeat LutzJin ChengB. Suman BharatiAlexey ProkudinJenq-wei YangRobert NitschUlf StraussHeiko EndleJunken AokiLeslie SchlüterJohannes VogtCarine ThalmanHeiko J. LuhmannAssunta Pelosisubject
0301 basic medicineCognitive NeuroscienceNeuronal OutgrowthHippocampusGlutamic AcidAxon hillockSynaptic Transmission03 medical and health sciencesCellular and Molecular NeuroscienceMice0302 clinical medicinePostsynaptic potentialmedicinePremovement neuronal activityAnimalsbioactive phospholipidsCalcium SignalingAxonearly synchronized activityCells CulturedPhospholipidsChemistryOriginal ArticlesEntorhinal cortexPerforant pathActin cytoskeletonAxonsCell biologyCa2+-signalingentorhinal–hippocampal formation030104 developmental biologymedicine.anatomical_structureaxon outgrowthnervous systemCalcium030217 neurology & neurosurgeryMetabolic Networks and Pathwaysdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-12-24 | Cerebral cortex (New York, N.Y. : 1991) |