Serotonin plays a central role in human mood disorders and is thought to function by modulating response to neurotransmitters. We are using the C. elegans egg-laying circuit to provide the first detailed example of how serotonin regulates a neural circuit at a cellular and molecular level. Egg laying occurs when the Hermaphrodite Specific Neurons (HSNs) release serotonin to cause two vulval muscle types, the
vm1s and
vm2s, to contract and open the vulva. Past studies1 suggest that during every body bend, the
vm1s receive an excitatory signal from cell(s) other than the HSNs, but typically this is a subthreshold excitatory signal that does not evoke egg laying. If that were the case, the role of serotonin would be to make the vulval muscles more excitable so that the vulval muscles do contract in response to this excitatory signal2. Even so, no major synapses onto the
vm1s have been identified, so the source of the hypothesized
vm1 excitatory signal has remained unknown. In the course of our studies of two G protein-coupled receptor fosmid-based reporters (DOP-5::GFP and DOP-6::GFP), we observed a set of neural branches emerge from the right ventral nerve cord just anterior and posterior to the vulva and terminate in varicosities that lie over the anterior and posterior
vm1s. These neural branches, which have never been described previously, form starting at the late L4 stage at the same time as the rest of the egg-laying system differentiates. We hypothesize that these neural branches form synapses onto the
vm1s and provide the excitatory signal that is potentiated by serotonin to trigger vulval muscle contraction and egg laying. Our work to identify the specific neuron(s) that make the branches so far suggests they are cholinergic neuron(s) other than the ventral cord motor neurons. Future experiments will confirm the identity of the neurons, test if they indeed form a synapse onto
vm1s, and utilize optogenetic tools to examine how manipulating their activity alters
vm1 muscle activity. This study will enable us to study how serotonin modulates responses to the excitatory signal in the neural circuit. 1Collins et al. (2016) Elife 5:
e21126. 2Brewer et al. (2019) PloS Genet 15:
e1007896.