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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 v s), that is 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 v s and high-voltage-activated Ca 2+ -channels (HVACCs), but also of NMDA receptors (NMDAR). Simulations show temporally overlapping HVACC- and NMDAR-mediated Ca 2+ -currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. This 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., Competing Interests: VL, LZ, GB, SA, MM, MS, VE No competing interests declared, BR BR is a founder of Femtonics Kft and a member of its scientific advisory board. No other competing interests exist., (© 2020, Lage-Rupprecht et al.)

Olfactory mitral cells extend lateral secondary dendrites that contact the lateral secondary and apical primary dendrites of other mitral cells in the external plexiform layer (EPL) of the olfactory bulb. The lateral dendrites further contact granule cell dendrites, forming dendrodendritic reciprocal synapses in the EPL. These dendritic structures are critical for odor information processing, but it remains unknown how they are formed. We recently showed that the immunoglobulin-like cell adhesion molecule nectin-1 constitutes a novel adhesion apparatus at the contacts between mitral cell lateral dendrites, between mitral cell lateral and apical dendrites, and between mitral cell lateral dendrites and granule cell dendritic spine necks in the deep sub-lamina of the EPL of the developing mouse olfactory bulb and named them nectin-1 spots. We investigated here the role of the nectin-1 spots in the formation of dendritic structures in the EPL of the mouse olfactory bulb. We showed that in cultured nectin-1-knockout mitral cells, the number of branching points of mitral cell dendrites was reduced compared to that in the control cells. In the deep sub-lamina of the EPL in the nectin-1-knockout olfactory bulb, the number of branching points of mitral cell lateral dendrites and the number of dendrodendritic reciprocal synapses were reduced compared to those in the control olfactory bulb. These results indicate that the nectin-1 spots regulate the branching of mitral cell dendrites in the deep sub-lamina of the EPL and suggest that the nectin-1 spots are required for odor information processing in the olfactory bulb., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Neurons typically receive synaptic input in their dendritic arbor, integrate inputs in their soma, and send output action potentials through their axon, following Cajal's law of dynamic polarization. Two notable exceptions are retinal amacrine cells and olfactory granule cells (GCs), which flout Cajal's edict by providing synaptic output from the same dendrites that collect synaptic input. Amacrine cells, a diverse cell class comprising >60 subtypes, employ various dendritic input/output strategies, but A17 amacrine cells (A17s) in particular share further interesting functional characteristics with GCs: both receive excitatory synaptic input from neurons in the primary glutamatergic pathway and return immediate, reciprocal feedback via GABAergic inhibitory synapses to the same synaptic terminals that provided input. Both neurons thereby process signals locally within their dendrites, shaping many parallels, signaling pathways independently. The similarities between A17s and GCs cast into relief striking differences that may indicate distinct processing roles within their respective circuits: First, they employ partially dissimilar molecular mechanisms to transform excitatory input into inhibitory output; second, GCs fire action potentials, whereas A17s do not. Third, GC signals may be influenced by cortical feedback, whereas the mammalian retina receives no such retrograde input. Finally, A17s constitute just one subtype within a diverse class that is specialized in a particular task, whereas the more homogeneous GCs may play more diverse signaling roles via multiple processing modes. Here, we review these analogies and distinctions between A17 amacrine cells and granule cells, hoping to gain further insight into the operating principles of these two sensory circuits. [ABSTRACT FROM AUTHOR]

The olfactory bulb differs from other brain regions by its use of bidirectional synaptic transmission at dendrodendritic reciprocal synapses. These reciprocal synapses provide tight coupling of inhibitory feedback from granule cell interneurons to mitral cell projection neurons in the accessory olfactory bulb (AOB), at the first stage of vomeronasal processing. It has been proposed that both the mGluR2 agonist DCG-IV and noradrenaline promote mate recognition memory formation by reducing GABAergic feedback on mitral cells. The resultant mitral cell disinhibition is thought to induce a long-lasting enhancement in the gain of inhibitory feedback from granule to mitral cells, which selectively gates the transmission of the learned chemosensory information. However, we found that local infusions of both noradrenaline and DCG-IV failed to disinhibit AOB neural activity in urethane-anaesthetised mice. DCG-IV infusion had similar effects to the GABAA agonist isoguvacine, suggesting that it increased GABAergic inhibition in the AOB rather than reducing it. Noradrenaline infusion into the AOB also failed to disinhibit mitral cells in awake mice despite inducing long-term increases in power of AOB local field potentials, similar to those observed following memory formation. These results suggest that mitral cell disinhibition is not essential for the neural changes in the AOB that underlie mate recognition memory formation in mice. [ABSTRACT FROM AUTHOR]

Synaptic interactions between the dendrites of mitral/tufted (MT) and granule cells (GCs) in the olfactory bulb are important for the determination of spatiotemporal firing patterns of MTs, which form an odor representation passed to higher brain centers. These synapses are subject to modulation from several sources originating both within and outside the bulb. We show that dopamine, presumably released by TH-positive local interneurons, reduces synaptic transmission from MTs to GCs. MT neurons express D2-1ike receptors (D2Rs), and both dopamine and the D2 agonist quinpirole decrease EPSC amplitude at the MT → GC synapse. D2R activation also increases paired pulse facilitation and decreases the frequency of action potential-independent spontaneous miniature EPSCs in GCs, consistent with an effect on MT glutamate release downstream from Ca2+ influx. Analysis of spike-evoked Ca2+ transients in MT lateral dendrites additionally shows that quinpirole reduces Ca2+ influx preferentially at distal locations, possibly by reducing dendritic excitability via increased transient K+ channel availability. When the OB is activated physiologically by using odor stimuli, blocking D2Rs increases the power of GABAA-dependent oscillations in the local field potential. This demonstrates a functional role for the dopaminergic circuit during normal odor-evoked responses and for the modulation of dendritic release and excitability in neuronal circuit function. Regulation of spike invasion of lateral dendrites by transient K+ currents also may provide a mechanism for local outputs of MTs to be controlled dynamically via other neuromodulators or by postsynaptic potentials. [ABSTRACT FROM AUTHOR]