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Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression
Chien-Po Liao1, Maryam Majeed1, Oliver Hobert1
1Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, NY 10027, USA.
Science Advances
|November 13, 2024
Summary
Early juvenile starvation in male worms alters brain wiring. This experience, mediated by serotonin and CREB, establishes lasting sexually dimorphic synaptic connections in the adult nervous system.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Early-life experiences significantly shape adult brain function, often with sex-specific outcomes.
- The molecular mechanisms underlying these long-term effects, particularly in establishing sexually dimorphic neural circuits, remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms by which juvenile experience establishes sexually dimorphic synaptic connectivity in the adult *Caenorhabditis elegans* nervous system.
Main Methods:
- Investigated the role of serotonin, CREB transcription factor, and FMI-1/Flamingo/CELSR in regulating synaptic connectivity.
- Utilized genetic and molecular techniques in *C. elegans* to track gene expression and neuronal connections.
Main Results:
- Juvenile male starvation disrupts serotonin-dependent CREB activation in the PHB sensory neuron.
- CREB signaling controls FMI-1 expression, which is crucial for PHB-AVA synaptic connectivity.
- A sex-specific regulatory cassette antagonizes FMI-1 in males, creating sexually dimorphic PHB-AVA connections.
Conclusions:
- Juvenile experience, specifically starvation in males, induces lasting sexually dimorphic synaptic connectivity via a serotonin-CREB-LIN-29-FMI-1 pathway.
- This study reveals a critical regulatory node (LIN-29) integrating multiple factors to establish experience-dependent, sex-specific neural circuits.
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