In the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) form reciprocal dendrodendritic synapses with large spines on GABAergic granule cells (GC), where unitary release of glutamate can trigger postsynaptic local activation of voltage-gated Na⁺-channels (Na_vs), i.e. a spine spike. Can such single MC input evoke reciprocal release? We find that unitary-like activation via two-photon uncaging of glutamate causes GC spines to release GABA both synchronously and asynchronously onto MC dendrites. This release indeed requires activation of Na_vs and high-voltage-activated Ca²⁺-channels (HVACCs), but also of NMDA receptors (NMDAR). Simulations show temporally overlapping HVACC- and NMDAR-mediated Ca²⁺-currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. The cooperative action of presynaptic NMDARs allows to implement synapse-specific, activity-dependent lateral inhibition and thus could provide an efficient solution to combinatorial percept synthesis in a sensory system with many receptor channels.

electrophysiology: whole cell recording of evoked inhibitory currents in voltage clamp from mitral cells in acute brain slices of juvenile rats

stimulation: two-photon uncaging of glutamate onto the reciprocal granule cell spines, guided by two-color two-photon imaging of mitral cell dendrites and granule cell spines (in VGAT-Venus rats)

processing: IGOR, Excel; the provided data contain all that is shown in the figures (example traces, cumulative data sets) but not every single experiment

simulations: NEURON/Python code for model and robustness testing; all files without prefix "Fig" are part of the simulation code

ultrastructure: analyses were made on pre-existing sections with immunogold labelling of NMDA receptors; cumulative data are provided

There is a Readme file enclosed with the simulation source code.