Neuron cilia constrain glial regulators to microdomains around distal neurons

Abstract

Each glia interacts with multiple neurons, but the fundamental logic of whether it interacts with all equally remains unclear. We find that a single sense-organ glia modulates different contacting neurons distinctly. To do so, it partitions regulatory cues into molecular microdomains at specific neuron contact-sites, at its delimited apical membrane. For one glial cue, K/Cl transporter KCC-3, microdomain-localization occurs through a two-step, neuron-dependent process. First, KCC-3 shuttles to glial apical membranes. Second, some contacting neuron cilia repel it, rendering it microdomain-localized around one distal neuron-ending. KCC-3 localization tracks animal aging, and while apical localization is sufficient for contacting neuron function, microdomain-restriction is required for distal neuron properties. Finally, we find the glia regulates its microdomains largely independently. Together, this uncovers that glia modulate cross-modal sensor processing by compartmentalizing regulatory cues into microdomains. Glia across species contact multiple neurons and localize disease-relevant cues like KCC-3. Thus, analogous compartmentalization may broadly drive how glia regulate information processing across neural circuits.