A specific folate activates serotonergic neurons to control C. elegans behavior

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Folates are essential B vitamins crucial for one-carbon metabolism.
• The precise mechanisms by which folates influence neuronal function and behavior are not fully understood.
• Serotonergic neurons play a key role in regulating various behaviors, including egg laying and feeding.

Purpose of the Study:

• To investigate the role of a specific folate in activating serotonergic neurons and modulating behavior in C. elegans.
• To elucidate the molecular pathway involved in folate-mediated neuronal activation, focusing on the folate receptor FOLR-1 and the GON-2 calcium channel.

Main Methods:

• Utilized C. elegans as a model organism.
• Investigated the physical interaction between FOLR-1 and GON-2 in a heterologous system.
• Examined the expression patterns of FOLR-1 and GON-2 in specific serotonergic neurons (HSN and NSM).
• Measured calcium (Ca2+) transients in HSN neurons and assessed egg-laying behavior.
• Evaluated the impact of 10-formyl-THF and pteroate on neuronal activity and behavior in a FOLR-1- and GON-2-dependent manner.
• Assessed the role of FOLR-1 and GON-2 in NSM neuron activation and starvation-induced behavioral responses.

Main Results:

• Identified a specific folate pathway activating serotonergic neurons (HSN and NSM) in C. elegans.
• Demonstrated that the folate receptor FOLR-1 and the calcium channel GON-2 are essential components of this pathway.
• Showed that both 10-formyl-THF and pteroate can induce calcium transients in HSN neurons and increase egg laying, dependent on FOLR-1 and GON-2.
• Confirmed that FOLR-1 and GON-2 are required for NSM neuron activation and proper behavioral responses to starvation.
• Found that FOLR-1 functions independently of canonical one-carbon metabolism.

Conclusions:

• 10-formyl-THF acts as a dietary signal that activates specific serotonergic neurons to influence behavior.
• The pathway involves the interaction of FOLR-1 and GON-2, leading to calcium entry into neurons.
• This novel pathway highlights a non-metabolic role for folates in regulating neuronal activity and behavior.