GPCR voltage dependence controls neuronal plasticity and behavior

G-protein coupled receptors are regulated by the membrane potential in vitro. Here, the authors show that muscarinic receptor voltage independence causes a strong behavioural effect of increased odour habituation, showing that these receptors are also in vivo modulated by the membrane potential. 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.

Automated summary

This study demonstrates that muscarinic receptors are regulated by membrane potential in vivo, impacting behavior, indicating the significant role of GPCR voltage dependence in neuronal coding and behavioral output.