Abstract
Neuron activity accompanies synapse formation and maintenance, but how early circuit activity contributes to behavior development is not well understood. Here, we use the Caenorhabditis elegans 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 C. elegans is driven by a homeostat that scales serotonin motor neuron activity in response to postsynaptic muscle feedback.SIGNIFICANCE STATEMENT The functional importance of early, spontaneous neuron activity in synapse and circuit development is not well understood. Here, we show in the nematode Caenorhabditis elegans 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 C. elegans egg-laying circuit activity and behavior.
Highlights
Developing neural circuits in the cortex, hippocampus, cerebellum, retina, and spinal cord show spontaneous neural activity (Wong et al, 1995; Garaschuk et al, 1998, 2000; Watt et al, 2009; Warp et al, 2012)
Because development of the cells in the circuit is known to be complete by the end of the L4 stage (Li and Chalfie, 1990), we wanted to determine the relationship between circuit development and the emergence of cell activity as the animals mature from juveniles into egg-laying adults
Unlike hermaphrodite-specific neurons (HSNs), we found the postsynaptic vulval muscles completed their morphological development during the L4.9 stage, just before the L4 molt
Summary
Developing neural circuits in the cortex, hippocampus, cerebellum, retina, and spinal cord show spontaneous neural activity (Wong et al, 1995; Garaschuk et al, 1998, 2000; Watt et al, 2009; Warp et al, 2012). Mature neural circuits show coordinated patterns of activity required to drive efficient behaviors. Activity-dependent mechanisms have been shown to play key roles during development in vertebrate neural circuits K.M.C. designed research; B.R. and J.G. performed research; B.R., J.G., and K.M.C. analyzed data; B.R. and K.M.C. wrote the paper. Strains used in this study have been provided to the C. elegans Genetics Center, which is funded by NIH Office of Research Infrastructure Programs (Grant P40 OD010440).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
