Presynaptic NMDA receptors (preNMDARs) control synaptic release, but it is not well understood how. Rab3-interacting molecules (RIMs) provide scaffolding at presynaptic active zones and are involved in vesicle priming. Moreover, c-Jun N-terminal kinase (JNK) has been implicated in regulation of spontaneous release. We demonstrate that, at connected layer 5 pyramidal cell pairs of developing mouse visual cortex, Mg2+-sensitive preNMDAR signaling upregulates replenishment of the readily releasable vesicle pool during high-frequency firing. In conditional RIM1αβ deletion mice, preNMDAR upregulation of vesicle replenishment was abolished, yet preNMDAR control of spontaneous release was unaffected. Conversely, JNK2 blockade prevented Mg2+-insensitive preNMDAR signaling from regulating spontaneous release, but preNMDAR control of evoked release remained intact. We thus discovered that preNMDARs signal differentially to control evoked and spontaneous release by independent and non-overlapping mechanisms. Our findings suggest that preNMDARs may sometimes signal metabotropically and support the emerging principle that evoked and spontaneous release are distinct processes. VIDEO ABSTRACT.
Pubmed ID: 29033205 RIS Download
Mesh terms: Animals | Excitatory Postsynaptic Potentials | Female | GTP-Binding Proteins | Magnesium | Male | Mice | Mice, Transgenic | Miniature Postsynaptic Potentials | Mitogen-Activated Protein Kinase 9 | Presynaptic Terminals | Pyramidal Cells | Receptors, N-Methyl-D-Aspartate | Receptors, Presynaptic | Visual Cortex
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Open source software application for laser scanning microscopy, electrophysiology, laser scanning photostimulation, and other physiological methods focused on neurobiology. Used to control laser scanning microscopes without need for custom data acquisition hardware. Standard data acquisition boards are used to acquire data and control laser scanning. The tasks of signal integration and image processing are placed on the computer CPU. Multiple versions of ScanImage are available, each with their own features.
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