Local reciprocal release of GABA from olfactory bulb granule cell spines: Cooperation of conventional release mechanisms and NMDA receptors

Abstract

Abstract In the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) engage in reciprocal dendrodendritic interactions with the large spines of GABAergic granule cells (GC), where unitary release of glutamate gives rise to a postsynaptic local activation of voltage-gated Na+ channels (Nav), i.e. a spine spike. Can single MC inputs thus trigger reciprocal release? Here we show that unitary-like activation via two-photon uncaging of glutamate causes GC spines to release GABA both synchronously and asynchronously onto MC dendrites, detected as IPSCs at the MC soma. This release indeed requires activation of Nav and high-voltage-activated Ca2+ channels (HVACCs), but also NMDA receptor (NMDAR) activation. Simulations show a substantial temporal overlap of HVACC- and NMDAR-mediated Ca2+ currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. Thus output from the GC spine reciprocal microcircuit relies on cooperative action of HVACCs and presynaptic NMDARs.