A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength. DKaiR1D is necessary in presynaptic motor neurons, localized near active zones, and confers robustness to the calcium sensitivity of baseline synaptic transmission. Acute pharmacological blockade of DKaiR1D disrupts homeostatic plasticity, indicating that this receptor is required for the expression of this process, distinct from developmental roles. Finally, we demonstrate that calcium permeability through DKaiR1D is necessary for baseline synaptic transmission, but not for homeostatic signaling. We propose that DKaiR1D is a glutamate autoreceptor that promotes robustness to synaptic strength and plasticity with active zone specificity. [Display omitted] •DKaiR1D is a glutamate receptor localized to presynaptic active zones•DKaiR1D is necessary for the expression, but not induction, of homeostatic plasticity•Calcium imaging at active zones reveals functional DKaiR1D activity•NMDA disrupts DKaiR1D activity and homeostatic plasticity in vivo Homeostatic mechanisms stabilize synaptic strength with remarkable specificity. Kiragasi et al. reveal that a presynaptic glutamate receptor (DKaiR1D) is localized near active zones and is required for homeostatic synaptic plasticity. Autocrine glutamatergic signaling at specific release sites may therefore enable the homeostatic modulation of neurotransmitter release.