Metabotropic Acetylcholine and Glutamate Receptors Mediate PI(4,5)P2 Depletion and Oscillations in Hippocampal CA1 Pyramidal Neurons in situ

Scientific Reports
Sandra Hackelberg, Dominik Oliver

Abstract

The sensitivity of many ion channels to phosphatidylinositol-4,5-bisphosphate (PIP2) levels in the cell membrane suggests that PIP2 fluctuations are important and general signals modulating neuronal excitability. Yet the PIP2 dynamics of central neurons in their native environment remained largely unexplored. Here, we examined the behavior of PIP2 concentrations in response to activation of Gq-coupled neurotransmitter receptors in rat CA1 hippocampal neurons in situ in acute brain slices. Confocal microscopy of the PIP2-selective molecular sensors tubbyCT-GFP and PLCδ1-PH-GFP showed that pharmacological activation of muscarinic acetylcholine (mAChR) or group I metabotropic glutamate (mGluRI) receptors induces transient depletion of PIP2 in the soma as well as in the dendritic tree. The observed PIP2 dynamics were receptor-specific, with mAChR activation inducing stronger PIP2 depletion than mGluRI, whereas agonists of other Gαq-coupled receptors expressed in CA1 neurons did not induce measureable PIP2 depletion. Furthermore, the data show for the first time neuronal receptor-induced oscillations of membrane PIP2 concentrations. Oscillatory behavior indicated that neurons can rapidly restore PIP2 levels during persistent activat...Continue Reading

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Citations

Feb 19, 2020·The Journal of General Physiology·Vincent RobertRebecca A Piskorowski
Jun 10, 2020·Canadian Journal of Physiology and Pharmacology·Hang XingXiong Han
Oct 6, 2020·Frontiers in Computational Neuroscience·Adam MergenthalTheodore W Berger
Jun 21, 2021·The Journal of Physiology·Sandesh MohanYoel Yaari

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