/UR/ BN, Duppé/ Advent Season is associated with scents of cinnamon or candle smoke – even if there are no Christmas markets this year. While the origin of visual and auditory impressions has been largely elucidated, we only know in part how and at which level of the brain olfactory signals are mapped and how olfactory sensations evolve. The first level of processing beyond the nose is the so-called olfactory bulb, whose neurons are innervated by the olfactory sensory cells.

Most neurons pf the mammalian brain have small protrusions, so-called spines, on their dendrites (i.e. the cell processes) where the synaptic contacts to the upstream neurons are generally situated. The granule cells of the olfactory bulb – a kind of local neuron and the most common type of neuron in this area of the brain – have spines that not only receive excitatory input signals, but can also release messenger substances themselves, so-called reciprocal synapses.

Signal, simulation, ultrastructure: functioning principle of the reciprocal granule cell spin. Left: Reciprocal electrical signals in response to 2-photon uncaging of glutamate. Top center: simulation of synaptic calcium currents. Bottom center: electron micrograph of the reciprocal spin. Right: pattern of reciprocal processing. © V. Egger

With high-resolution optical methods, a team of scientists led by Veronica Egger, Professor of Neurophysiology at the University of Regensburg, was the first to demonstrate experimentally that the release of neurotransmitters from these reciprocal spines ensues from an action potential confined to the spine. Surprisingly, triggering the release requires the simultaneous activation of so-called NMDA receptors, which are otherwise relevant for the generation of input signals. In collaboration with colleagues from Tehran and Turin, a likely mechanism for such a novel cooperation could be described. The results of the work have now been published in the journal eLife.

Beyond these unusual subcellular processes, this entails broader significance for the encoding of olfactory stimuli. As each scent molecule typically activates a large number of scent receptors, this is a deductive process. All receptors of the same type now excite a downstream module of neurons of the bulbus olfactorius, which in turn is interconnected with the olfactory cortex. From this activation of multiple modules, a scent perception is synthesized (just as a musical chord activates multiple groups of frequency-selective neurons in the auditory pathway, eventually resulting in a perception of the overall sound). The receptor modules do not interact directly in the bulb, but are interconnected, amongst others, via granule cells. The observed cooperation suggests that the synthesis of olfactory perception already starts at the level of the bulbus olfactorius in a very efficient way, such that the granule cells exclusively interconnect simultaneously active modules and synchronize the activity of these modules.

The project received major funding from the German Federal Ministry of Education and Research (grant numbers 01GQ1104 and 01GQ1410A).

>> original press release (German text)

Original publication

Lage-Rupprecht, V., Zhou, L., Bianchini, G., Aghvami, S. S., Mueller, M., Rózsa, B., Sassoè-Pognetto, Egger, V. (2020). Presynaptic NMDARs cooperate with local spikes toward GABA release from the reciprocal olfactory bulb granule cell spine. eLife 2020;9:e63737. DOI:10.7554/eLife.63737