One evolutionarily constant feature of the vertebrate odor processing network in the OB are the glomeruli (Hildebrand and Shepherd, 1997; Strausfeld and Hildebrand, 1999). Even though they are of variable shapes and sizes in different vertebrate species or olfactory subsystems, they share a general input-output structure (Figure 5). The spheroid glomerular structures are composed of RN axon terminals forming synapses with the dendrites of several projection neurons, which in turn project their axons to a variety of higher brain centers. Additionally, different types of interneurons form synapses with the other components in the glomeruli and interfere with odor processing via inhibitory or modulatory synapses (Firestein, 2001; Nagayama et al., 2014). However, several components of the OB circuit vary across vertebrates and the lack of comparative studies makes it difficult to predict, whether the differences in circuit architecture have immediate effects on olfactory perceptions (Eisthen, 1997; Eisthen and Polese, 2007).
A general evolutionary trend is an increasing degree of laminar organization in the OB and a clear spatial segregation of different neuronal subtypes (Eisthen and Polese, 2007; Nieuwenhuys, 1966). In the early diverging sea lamprey, somata of projection neurons are mostly intermingled within the glomeruli and extend one or multiple primary dendrites towards mostly a single glomerulus (Figure 5A), where they form extensive arborizations (Dryer and Graziadei, 1994; Green et al., 2013; Iwahori et al., 1987). Similarly, the few examined cartilaginous fishes exhibit uni-glomerular projection neurons in close proximity to the glomerular neuropil (Dryer and Graziadei, 1993, 1994). These projection neurons solely have primary dendrites that receive direct glomerular input, while non-glomerular
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lateral dendrites are lacking. More caudally, the somata of inhibitory interneurons, the granule cells, are located (Nieuwenhuys, 1966). They have been shown to extend several dendrites to multiple glomeruli, putatively facilitating cross-talk between individual glomeruli (Dryer and Graziadei, 1994).
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In ray-finned fishes, the circuit architecture seems to differ between species. Distinct layers are generally ill-defined (Satou, 1990) and some fishes like the zebrafish exhibit mostly uni-glomerular projection neurons (Fuller et al., 2006; Figure 5A), others have multi-glomerular projection neurons (Oka, 1983; Figure 5A). With the emergence of the first tetrapods, the segregation of distinct horizontal layers becomes more apparent. The primary dendritic branches of the projection neurons in amphibians are generally longer than in fishes and exhibit lateral non-glomerular branches (asterisks, Figure 5A) that give rise to the external plexiform layer (Nezlin et al., 2003; Nieuwenhuys, 1966; Scalia et al., 1991a). Single projection neurons connect to one or more glomeruli (Figure 5A) and some authors also distinguished different types of projection neurons based on their distance from the glomeruli (Dryer and Graziadei, 1994; Herrick, 1924; Jiang and Holley, 1992a; Scalia et al., 1991a). Like in fishes, the inhibitory granule cell somata are located caudally to the projection neuron somata, in the granule cell layer. In contrast to their fish counterparts, they form synapses with the lateral, non-glomerular dendrites of the projection and barely reach into the non-glomerular neuropil (Dryer and Graziadei, 1994). In the interglomerular space, some periglomerular interneurons were also described in both the MOB and the AOB of amphibians (Nezlin and Schild, 2000; Nezlin et al., 2003; Nieuwenhuys, 1966). Similarly, reptile projection neurons are mostly multi-glomerular and bear lateral dendrites in both the MOB (Garcia-Verdugo et al., 1986; Iwahori et al., 1989) as well as the AOB (Iwahori et al., 1989; Llahi and García-Verdugo, 1989).
The rodent MOB shows a well-organized layering and the glomerular neuropil is delineated by a high number of variable cells that are usually grouped together as juxtaglomerular cells (Nagayama et al., 2014; Pinching and Powell, 1971). The projection neurons are segregated into the tufted cells and the mitral cells, which are located closer and further from the glomeruli, respectively (Macrides and Schneider, 1982; Nagayama et al., 2014). Both cell types only connect to a single glomerulus (Figure 5B, left panel) and have multiple lateral dendrites (Orona et al., 1984), but have different axonal target structures and putatively different functions (Nagayama, 2010). In contrast, the AOB glomeruli are Figure 5 Glomerular wiring in the vertebrate OB.
A) Representative schematics of one OB hemisphere of jawless fishes, ray finned fishes and anurans are shown.
Glomeruli are highlighted by dotted circles. Projection neurons are generally connecting to a single glomerulus in the jawless fish, while both uni- and multi-glomerular projection neurons are reported from ray finned fishes and amphibians. Amphibian projection neurons are distinct from the fish projection neurons by the presence of lateral dendrites (asterisks). B) Glomerular wiring in the MOB (left) and the AOB (right) of rodents. Individual RNs in the rodent MOE and VNO express one allele of a single olfactory receptor gene (A and B) or vomeronasal receptor gene (C and D), respectively. In the main olfactory system, all RNs expressing the same allele project their axons to two glomeruli in the MOB. Each projection neuron (mitral/tufted cells) connects to a single glomerulus. In the accessory olfactory system, all RNs expressing the same vomeronasal receptor allele project to multiple glomeruli and each projection neurons gets input from multiple glomeruli. Data is based on the following publications (Dryer and Graziadei, 1994; Mombaerts et al., 1996; Del Punta et al., 2002b; Ressler et al., 1994; Rodriguez et al., 1999; Vassar et al., 1994). A anterior, AOB accessory olfactory bulb, L lateral, M medial, MOB main olfactory bulb, MOE main olfactory epithelium, OB olfactory bulb, ON olfactory nerve, P posterior, VNO vomeronasal organ.
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generally smaller and less clearly delineated. Mitral and tufted cells are not distinguished (Larriva-Sahd, 2008; Mohrhardt et al., 2018; Takami and Graziadei, 1991). Their dendritic configuration is more reminiscent of the reptile/amphibian projection neurons, since they connect to up to 10 distinct glomeruli (Larriva-Sahd, 2008; Takami and Graziadei, 1991; Yonekura and Yokoi, 2008; Figure 5B, right panel).
In the rodent MOB, all RNs expressing the same allele of a single olfactory receptor gene converge onto one (or two) glomerulus in the MOB (Figure 5B, left panel). The information encoded by the glomerulus is then transmitted to the population of projection neurons that connect to it via their uni-glomerular dendrite. This forms a single unit all dependent on the odor features detected by a single receptor protein (Figure 5B, left panel). However, in the AOB, all RNs expressing the same receptor allele converge onto multiple glomeruli, and each projection neuron receives input from multiple glomeruli (Figure 5B, right panel). It is not clear yet, whether the information received at the various dendritic branches all originate from homotypic glomeruli (Del Punta et al., 2002b) or if they integrate between different glomerular information channels (Wagner et al., 2006). To complicate things further, some of axons in the rodent AOB were shown to bifurcate, terminating in multiple glomeruli (Larriva-Sahd, 2008), violating the general idea that individual RN axons are unbranched before entering a single glomerulus (Klenoff and Greer, 1998; Mombaerts, 2006). A similar pattern was observed in both the MOB as well as the AOB of Xenopus laevis (Hassenklöver and Manzini, 2013;
Nezlin and Schild, 2005). Data of most other animal groups are missing in regard. It remains elusive, whether a certain olfactory wiring scheme facilitates a certain olfactory function, if wiring patterns correlate with ligands or specific environments, or if they are evolutionary strategies of specific vertebrate lineages.