Olfactory bulb granule cells: specialized to link coactive glomerular columns for percept generation and discrimination of odors

Abstract

The role of granule cells in olfactory processing is surrounded by several enigmatic observations, such as the purpose of reciprocal spines and the mechanisms for GABA release, the apparently low firing activity and recurrent inhibitory drive of granule cells, the missing proof for functional reciprocal connectivity, and the apparently negligible contribution to lateral inhibition. Here, we summarize recent results with regard to both the mechanisms of GABA release and the behavioral relevance of granule cell activity during odor discrimination. We outline a novel hypothesis that has the potential to resolve most of these enigmas and allows further predictions on the function of granule cells in odor processing. Briefly, recent findings imply that GABA release from the reciprocal spine requires a local spine action potential and the cooperative action of NMDA receptors and high voltage-activated Ca2+ channels. Thus, lateral inhibition is conditional on activity in the principal neurons connected to a granule cell and tightly intertwined with recurrent inhibition. This notion allows us to infer that lateral inhibition between principal neurons occurs “on demand,” i.e., selectively on coactive mitral and tufted cells, and thus can provide directed, dynamically switched lateral inhibition in a sensory system with 1000 input channels organized in glomerular columns. The mechanistic underpinnings of this hypothesis concur with findings from odor discrimination behavior in mice with synaptic proteins deleted in granule cells. In summary, our hypothesis explains the unusual microcircuit of the granule cell reciprocal spine as a means of olfactory combinatorial coding.

Neuronal Adenosine A1 Receptor is Critical for Olfactory Function but Unable to Attenuate Olfactory Dysfunction in Neuroinflammation

“…Here mitral cells are forming dendro-dendritic synapses with several GABAergic interneurons, mainly granular cells. These reciprocal connections are involved in recurrent and lateral inhibition of excited mitral cells by granule cells ( Isaacson and Strowbridge, 1998 ; Egger and Kuner, 2021 ). Schematic representation is shown in Figure 2A .…”

Principles of odor coding in vertebrates and artificial chemosensory systems

“…In rodents, many different morphological types of GCs have been distinguished (893). All GCs are generally axonless GABAergic inhibitory interneurons, they have a relatively small soma [6-8 mm in diameter (828 and references therein)], and they project several spiny dendrites mainly into the EPL, where they form characteristic dendro-dendritic reciprocal synapses mainly with secondary dendrites of MCs and TCs (828,(891)(892)(893). Deep SACs are another heterogeneous cell population in the GCL (FIGURE 16).…”

“…After the first processing and modulation steps within the GL, a second step of intrinsic modulation takes place a little deeper in the OB, mainly driven by a characteristic interaction between PNs and GCs (FIGURE 16). The axonless GABAergic GCs are inhibitory interneurons that project several spiny dendrites mainly into the EPL, where they form dendro-dendritic reciprocal synapses with MCs and TCs (828,832,891,996). At these prominent synapses, a recurrent inhibition of PNs takes place, i.e., activated PNs release glutamate onto GCs, which in turn inhibit the PNs by releasing GABA back onto them (834,868,885,997,998).…”

Anatomical and Functional Connectivity at the Dendrodendritic Reciprocal Mitral Cell–Granule Cell Synapse: Impact on Recurrent and Lateral Inhibition

“…However, the used methods are quite diverse in their approaches and both glomerular layer and EPL circuits may well contribute to both isotropic (i.e., radially symmetric) and anisotropic (i.e., patchy) lateral inhibition across glomerular columns. Based on others' and own functional observations (Arevian et al, 2008;Fukunaga et al, 2014;Bywalez et al, 2015;Burton, 2017;Lage-Rupprecht et al, 2020;Mueller and Egger, 2020), we devised a hypothesis on the role of GCs in olfactory processing, which states that GCs serve to provide lateral inhibition exclusively between coactivated glomerular columns via an activity-dependent mechanism located within the reciprocal spines (Lage-Rupprecht et al, 2020;Egger and Kuner, 2021). This hypothesis could reconcile the abovementioned divergent findings on the spatial structure of lateral inhibition.…”