Past experience shapes sexually dimorphic neuronal wiring through monoaminergic signaling

Differences in female and male brains exist across the animal kingdom and extend from molecular to anatomical features. We show here that sexually dimorphic anatomy, gene expression, and function in the nervous system can be modulated by past experiences. In the nematode C. elegans, sexual differentiation entails the sex-specific synaptic pruning of synaptic connections between sex-shared neurons, giving rise to sexually dimorphic circuits in adult animals (1). We discovered that starvation during juvenile stages is memorized in males to suppress the emergence of sexually dimorphic synaptic connectivity. These circuit changes confer increased chemosensory responsiveness in adult males following juvenile starvation. We find that an octopamine-mediated starvation signal dampens serotonin production to convey the memory of starvation. Serotonin production is monitored by a 5-HT1A serotonin receptor homolog which acts cell-autonomously to promote the pruning of sexually dimorphic synaptic connectivity under well-fed conditions. Our studies demonstrate how life history can impact neurotransmitter production, synaptic connectivity, and behavioral output in a sexually dimorphic circuit.