Criteria for Assigning a Neurotransmitter Function in C. elegans
For detailed information on specific neurotransmitters see: The Evidence for Classical Neurotransmitters in C. elegans Neurons
By classical definition, for a substance to be accepted as a neurotransmitter of a particular neuron, it must meet certain criteria1.
2Although most cells that release a neurotransmitter also synthesize the neurotransmitter, this criterion has recently been expanded beyond synthesis alone, to include less common cells that do not synthesize, but instead take up the neurotransmitter from the vicinity and then re-release it. We refer to these neurons as 'uptake-dependent.'
For technical reasons, the traditional criteria cannot be fully met for putative neurotransmitters in C. elegans (especially criteria 2 and 3). The advent of new microfluidic devices coupled with optical stimulation may soon overcome the difficulties currently encountered in the worm for isolation and analysis of substances following stimulated release (i.e., traditional physiological techniques to identify a chemical as a neurotransmitter). Nevertheless, a large body of 'circumstantial' evidence indicates that various neurotransmitters are used by specific neurons in the worm. From the available evidence, we may propose a modified set of criteria that will suffice to identify the neurotransmitter(s) used by a particular neuron in the worm, despite the inability to fulfill all the traditional criteria.
Reasonable criteria for identifying a neurotransmitter as functioning in a C. elegans neuron:
Definition and use of the suffix '-ergic'
Neurons that use a given neurotransmitter, fulfilling the above criteria, are referred to as 'neurotransmitter-ergic.' For example, neurons using glutamate are 'glutamatergic.' [See the table below for more examples.] We maintain that the suffix '-ergic' indicates a neuron that functionally uses or 'works with' the neurotransmitter. [2. exhibiting or stimulating activity esp. of (such) a neurotransmitter substance <adrenergic> <dopaminergic> - Merriam-Webster Medical Dictionary definition]. This fits with the etymology of -ergy, work [from Latin -ergia, work; from Greek, ergon work], such that -ergic means to 'work with' a neurotransmitter [see also here].
This would also include neurons that do not synthesize the transmitter, but take it up, package and release the transmitter to affect postsynaptic cells. Such neurons may be called 'uptake-dependent' -ergic neurons. In C. elegans, the hermaphrodite neurons VC4 and VC5 may not make their own serotonin (serotonin-synthetic enzyme genes are not expressed there), but take it up, package it and release it to modulate egg laying (see note33 here). These cells are therefore 'uptake-dependent' serotonergic neurons.
Note that the adjectival form is also sometimes used to describe receptors that bind and are activated by the neurotransmitter ('β2 adrenergic receptor'), for specific synapses at which the transmitter is used ('cholinergic synapse'), and for circuits, pathways or systems in the brain or nervous system ('dopaminergic pathways') that use a given neurotransmitter. Within such pathways or systems, a neuron may be referred to as 'dopaminergic' based simply on the presence of the transmitter in the cell, on a presumption of its function.
This section should be cited as: Loer, C. M.§ 2022. Criteria for Assigning a Neurotransmitter Function in C. elegans, in WormAtlas. doi:10.3908/wormatlas.5.201