Inhibitory peptidergic modulation ofC. elegansserotonin neurons is gated by T-type calcium channels.
Serotonin is an evolutionarily ancient molecule that functions in generating and modulating many behavioral states. Although much is known about how serotonin acts on its cellular targets, how serotonin release is regulatedin vivoremains poorly understood. In the nematodeC. elegans,serotonin neurons that drive female reproductive behavior are directly modulated by inhibitory neuropeptides. Here, we report the isolation of mutants in which inhibitory neuropeptides fail to properly modulate serotonin neurons and the behavior they mediate. The corresponding mutations affect the T-type calcium channel CCA-1 and symmetrically re-tune its voltage-dependencies of activation and inactivation towards more hyperpolarized potentials. This shift in voltage dependency strongly and specifically bypasses the behavioral and cell physiological effects of peptidergic inhibition on serotonin neurons. Our results indicate that T-type calcium channels are critical regulators of aC. elegansserotonergic circuit and demonstrate a mechanism in which T-type channels functionally gate inhibitory modulationin vivo.
Skirball Institute for Biomolecular Medicine, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Department of Cell Biology, NYU Langone School of Medicine, New York, United States.
Kara E
KE
Zang
Skirball Institute for Biomolecular Medicine, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Department of Cell Biology, NYU Langone School of Medicine, New York, United States.
Elver
E
Ho
Skirball Institute for Biomolecular Medicine, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Department of Cell Biology, NYU Langone School of Medicine, New York, United States.
Niels
0000-0002-8679-2269
N
Ringstad
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000502:physiology*
D020747:Calcium Channels, T-Type; D009479:Neuropeptides
C. elegans; behavioral genetics; calcium channels; neuromodulation; neuropeptides; neuroscience; serotonin