Homeostatic Feedback Modulates the Development of Two-State Patterned Activity in a Model Serotonin Motor Circuit in Caenorhabditis elegans

• Published in: The Journal of neuroscience Vol. 38; no. 28; pp. 6283 - 6298
• Main Authors: Ravi, Bhavya, Garcia, Jessica, Collins, Kevin M
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 11-07-2018
• Subjects: Accumulation; Adults; Caenorhabditis elegans; Calcium; Calcium imaging; Circuits; Egg laying; Eggs; Feedback; Hermaphrodites; Larvae; Motors; Muscle function; Muscles; Nematodes; Rhythms; Serotonin; Sterilization; Synaptogenesis; Uterus; C. elegans; serotonin; calcium; circuit; behavior; developmental biology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.3658-17.2018

Neuron activity accompanies synapse formation and maintenance, but how early circuit activity contributes to behavior development is not well understood. Here, we use the
egg-laying motor circuit as a model to understand how coordinated cell and circuit activity develops and drives a robust two-state behavior in adults. Using calcium imaging in behaving animals, we find the serotonergic hermaphrodite-specific neurons (HSNs) and vulval muscles show rhythmic calcium transients in L4 larvae before eggs are produced. HSN activity in L4 is tonic and lacks the alternating burst-firing/quiescent pattern seen in egg-laying adults. Vulval muscle activity in L4 is initially uncoordinated but becomes synchronous as the anterior and posterior muscle arms meet at HSN synaptic release sites. However, coordinated muscle activity does not require presynaptic HSN input. Using reversible silencing experiments, we show that neuronal and vulval muscle activity in L4 is not required for the onset of adult behavior. Instead, the accumulation of eggs in the adult uterus renders the muscles sensitive to HSN input. Sterilization or acute electrical silencing of the vulval muscles inhibits presynaptic HSN activity and reversal of muscle silencing triggers a homeostatic increase in HSN activity and egg release that maintains ∼12-15 eggs in the uterus. Feedback of egg accumulation depends upon the vulval muscle postsynaptic terminus, suggesting that a retrograde signal sustains HSN synaptic activity and egg release. Our results show that egg-laying behavior in
is driven by a homeostat that scales serotonin motor neuron activity in response to postsynaptic muscle feedback.
The functional importance of early, spontaneous neuron activity in synapse and circuit development is not well understood. Here, we show in the nematode
that the serotonergic hermaphrodite-specific neurons (HSNs) and postsynaptic vulval muscles show activity during circuit development, well before the onset of adult behavior. Surprisingly, early activity is not required for circuit development or the onset of adult behavior and the circuit remains unable to drive egg laying until fertilized embryos are deposited into the uterus. Egg accumulation potentiates vulval muscle excitability, but ultimately acts to promote burst firing in the presynaptic HSNs which results in egg laying. Our results suggest that mechanosensory feedback acts at three distinct steps to initiate, sustain, and terminate
egg-laying circuit activity and behavior.