GPCR voltage dependence controls neuronal plasticity and behavior

Eyal Rozenfeld, Merav Tauber, Yair Ben-Chaim, Moshe Parnas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

G-protein coupled receptors (GPCRs) play a paramount role in diverse brain functions. Almost 20 years ago, GPCR activity was shown to be regulated by membrane potential in vitro, but whether the voltage dependence of GPCRs contributes to neuronal coding and behavioral output under physiological conditions in vivo has never been demonstrated. Here we show that muscarinic GPCR mediated neuronal potentiation in vivo is voltage dependent. This voltage dependent potentiation is abolished in mutant animals expressing a voltage independent receptor. Depolarization alone, without a muscarinic agonist, results in a nicotinic ionotropic receptor potentiation that is mediated by muscarinic receptor voltage dependency. Finally, muscarinic receptor voltage independence causes a strong behavioral effect of increased odor habituation. Together, this study identifies a physiological role for the voltage dependency of GPCRs by demonstrating crucial involvement of GPCR voltage dependence in neuronal plasticity and behavior. Thus, this study suggests that GPCR voltage dependency plays a role in many diverse neuronal functions including learning and memory.

Original languageEnglish
Article number7252
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

Funding

FundersFunder number
National Institute of General Medical SciencesP41GM103311
H2020 European Research Council
Open University of Israel
European Research Council676844
Deutsche Forschungsgemeinschaft408264519
Israel Science FoundationISF 343/18

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