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

Ria S Peesapati1, Brianna L Austin-Byler1, Fathima Zahra Nawaz1

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Nature Communications
|September 30, 2024
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A specific folate activates brain cells in C. elegans, influencing behavior via the folate receptor (FOLR-1) and a calcium channel (GON-2). This pathway impacts egg-laying and feeding behaviors.

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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.