Synaptic phospholipid signaling modulates axon outgrowth via glutamate-dependent Ca2+-mediated molecular pathways

Johannes Vogt, Sergei Kirischuk, Petr Unichenko, Leslie Schlüter, Assunta Pelosi, Heiko Endle, Jenq Wei Yang, Nikolai Schmarowski, Jin Cheng, Carine Thalman, Ulf Strauss, Alexey Prokudin, B. Suman Bharati, Junken Aoki, Jerold Chun, Beat Lutz, Heiko J. Luhmann, Robert Nitsch

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)131-145
Number of pages15
JournalCerebral Cortex
Volume27
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Axon outgrowth
  • Bioactive phospholipids
  • Ca2+-signaling
  • Early synchronized activity
  • Entorhinal-hippocampal formation

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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