Serotonin has emerged as a key neurotransmitter that regulates feeding behaviour. Targeting the serotonergic circuitry has therapeutic potential for human obesity, but the key molecules that regulate this circuitry are largely unknown. In Caenorhabditis elegans, it has been shown that serotonin enhances feeding behaviour, and that genetic ablation of tryptophan hydroxylase (tph-1; expressed in certain types of neuron and required for serotonin synthesis) reduces feeding. Cunningham et al. dissected this feeding circuit in more detail to identify additional, evolutionarily conserved components that control feeding behaviour. They show that deletion of tph-1 in chemosensory ADF neurons, but not in NSM pharyngeal neurons, reduces feeding behaviour. The circuit was found to require SER-5, a serotonin receptor, and hlh34, the worm homologue of human SIM1, which encodes a transcription factor expressed in the human paraventricular nucleus (a brain region crucial for maintaining energy homeostasis). Serotonin produced by ADF neurons was found to increase feeding behaviour by inhibiting the activity of AMP-activated kinase (AMPK), another conserved regulator of energy balance, in hlh34-expressing neurons. AMPK inhibition led to increased glutamate neurotransmitter release by hlh34-expressing neurons, stimulating regulation by glutamate-responsive pharyngeal neurons. Finally, the authors demonstrate using rat hippocampal neurons that at least some aspects of this feeding-regulatory circuit also operate in mammals.
The serotonergic feeding-regulatory circuit: learning from worms
- Split-screen
- Views Icon Views
-
Article Versions Icon
Versions
- Version of Record 01 September 2012
- Share Icon Share
-
Tools Icon
Tools
- Search Site
The serotonergic feeding-regulatory circuit: learning from worms. Dis Model Mech 1 September 2012; 5 (5): 567. doi:
Download citation file:
Advertisement
Cited by
Special Issue: The RAS Pathway

Our latest special issue is now complete. It showcases RAS-driven mechanisms of disease progression, and highlights approaches to treat and modify the disease course in model systems.
Call for papers: Moving Heart Failure to Heart Success

Disease Models & Mechanisms is pleased to welcome submissions for consideration for an upcoming special issue, Moving Heart Failure to Heart Success: Mechanisms, Regeneration & Therapy. The deadline for submitting articles to the special issue has been extended to 1 August 2022.
Propose a new Workshop

Our Workshops bring together leading experts and early-career researchers from a range of scientific backgrounds. Applications are now open to propose Workshops for 2024, one of which will be held in a Global South country. .
A focus on Drosophila

In a series of front section articles, DMM is highlighting the versatility, breadth, and scope of Drosophila research in human disease modelling and translational medicine.
Apply for a DMM Conference Travel Grant

Aimed at early-career researchers wanting to attend in-person and virtual meetings, the next application deadline for a DMM Conference Travel Grant is 6 June 2022. Find out more and hear from past recipients about their experience of the grant.
Other journals from
The Company of Biologists