Topographic organization in the olfactory bulb

Cell and Tissue Research https://doi.org/10.1007/s00441-020-03348-w REVIEW Topographic organization in the olfactory bulb Claudia Lodovichi1 Received: 21 September 2020 / Accepted: 10 November 2020 © The Author(s) 2021 Abstract The ability of the olfactory system to detect and discriminate a broad spectrum of odor molecules with extraordinary sensitivity relies on a wide range of odorant receptors and on the distinct architecture of neuronal circuits in olfactory brain areas. More than 1000 odorant receptors, distributed almost randomly in the olfactory epithelium, are plotted out in two mirror-symmetric maps of glomeruli in the olfactory bulb, the first relay station of the olfactory system. How does such a precise spatial arrangement of glomeruli emerge from a random distribution of receptor neurons? Remarkably, the identity of odorant receptors defines not only the molecular receptive range of sensory neurons but also their glomerular target. Despite their key role, odorant receptors are not the only determinant, since the specificity of neuronal connections emerges from a complex interplay between several molecular cues and electrical activity. This review provides an overview of the mechanisms underlying olfactory circuit formation. In particular, recent findings on the role of odorant receptors in regulating axon targeting and of spontaneous activity in the development and maintenance of synaptic connections are discussed. Keywords Olfactory bulb · Neuronal circuits · Topographic map · Odorant receptor · Electrical activity Introduction The specificity of synaptic connections among neurons is essential to transform the electrical activity into meaningful neuronal codes. In most sensory modalities, nearby receptor neurons in the periphery project to nearby neurons in the target area, thereby maintaining spatial order. This spatial segregation of sensory afferents results in a “continuous” topographic map that encodes the quality, the intensity, and the location of sensory stimuli. In this paradigm, distinct features of sensory stimuli are analyzed according to the spatial distribution of receptor neurons in the periphery. This spatial pattern is faithfully maintained in higher brain areas where sensory information is processed to provide an internal representation of the external world (Kaas 1997; Feldheim and O’Leary 2010). The olfactory system differs from this organizational plan, in several ways. In the peripheral structure, i.e., the olfactory epithelium, receptor neurons are almost randomly * Claudia Lodovichi ; 1 Neuroscience Institute CNR, Department of Biomedical Science, Veneto Institute of Molecular Medicine, Padova Neuroscience Center, Padova, Italy distributed. Spatial order is achieved in the olfactory bulb (OB), the first olfactory brain area, where sensory neurons expressing the same odorant receptor (OR) converge with exquisite precision to form glomeruli in invariant locations, resulting in the topographic map of the olfactory bulb (Mombaerts et al. 1996; Mombaerts 2001). In this case, the identity of the OR instructs the topography of the bulb, which results in thousands of discrete units, i.e., glomeruli. This spatial segregation of sensory afferents provides a “discrete” sensory map, where the quality and intensity of odor stimuli are encoded. Noteworthy, olfactory sensory neurons (OSNs) regenerate throughout life and constantly reform precise synaptic connections with the target field (Shepherd 2004). How does a highly spatial organization in the OB emerge from a random distribution of receptor neurons in the periphery? Compelling evidence indicates that ORs are involved not only in odor detection but also in the formation of the sensory map (Wang et al. 1998). Although ORs play a critical role in the OB topography, a complex interaction among ORs, other molecular cues, and electrical activity is required to carve the final configuration of the neuronal architecture of the OB. This review provides an overview on olfactory circuit formation, with a focus on recent findings on the role of ORs and afferent spontaneous activity in the development and 13 Vol.:(0123456789) Cell and Tissue Research maintenance of neuronal circuits underlying the topography of the OB, in mice. Olfactory system organization: from the olfactory epithelium to the olfactory bulb Odors are sensed by OSNs located in the olfactory epithelium that lines the posterior part of the nasal cavity. OSNs are bipolar neurons with a small soma and a single apical dendrite that ends in a swelling formation named “knob,” from which several thin filamentous structures, i.e., cilia, depart. ORs are expressed on the cilia that protrude in the nasal cavity, where they encounter odors carried by the airflow. From the opposite pole of the OSN soma, a thin unmyelinated, unbranched axon emerges and crosses the cribriform plate to reach the OB, the first olfactory brain area (Shepherd 2004). ORs are seven transmembrane G-protein coupled receptors (Buck and Axel 1991) that upon binding odors activate specific olfactory G proteins, G olf, that stimulate adenylyl cyclase III (ACIII) to synthesize cAMP (Boekhoff and Breer 1990; Breer et al. 1990). Cyclic AMP then directly activates cyclic nucleotidegated (CNG) channels, leading to an influx of Na + and Ca2+ in sensory neurons (Liman and Buck 1994; Bradley et al. 2005). The rise of intracellular C a 2+ level opens C a 2+-activated-Cl − channels in the ciliary membrane, resulting in an efflux of C l − that further depolarizes the cell to generate action potentials (Breer 1994; Menini 1995, 1999; Buck 1996; Prasad and Reed 1999; Reisert et al. 2005; Kaupp 2010). The olfactory system has extraordinary discriminatory power, being able to detect a myriad of different odorant molecules, present in the environment even at very low concentrations. Such sophisticated discriminatory capacity relies on a wide repertoire of ORs and on a specific pattern of interaction between odors and ORs, named combinatorial code (Malnic et al. 1999). This code defines the ability of each OR to recognize multiple odors and of each odor to bind several ORs. Such complex interaction is made possible by distinct structural features in the odorant molecules, defined odotopes, that can interact with several ORs. In turn, each OR can recognize specific odotope in multiple odors (Malnic et al 1999). The specificity of the percept for a given odor is achieved by a unique combination of activated ORs. Given that the genome encodes more than 1000 ORs, this combinatorial receptor coding scheme allows the discrimination of a vast number of different odors. 13 Topographic organization of the olfactory bulb The olfactory map Unlike most sensory systems, the peripheral sheet of the olfactory system, i.e., the olfactory epithelium, exhibits a coarse topographic organization. Each OSN expresses only one in a repertoire of more than 1000 OR genes. The expression of a single ty (...truncated)