Topographic mapping--the olfactory system

Abstract

Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils--the olfactory glomeruli--that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.

Figure 1.

Olfactory sensory neuron projections along the dorsal–ventral axis in the mouse olfactory system. (A) Lateral view of a MOR28-IRES-tau-lacZ transgenic mouse (Serizawa et al. 2000) stained with X-gal to reveal OSNs in the OE and tau-lacZ-tagged MOR28 axons projecting to a specific site forming a glomerulus in the OB. (B) OSNs in the dorsomedial zone (D zone) in the OE project their axons to the dorsal domain (D domain) of the OB. Class I ORs are mostly expressed by OSNs in the D zone in the OE, which target the anterodorsal cluster of the D domain in the OB (red). In the ventrolateral zone (V zone), each class II OR possesses its own unique expression area, which is distributed in a continuous and overlapping manner along the dorsomedial–ventrolateral axis in the OE. The dorsomedial–ventrolateral expression area in the OE corresponds to the glomerular positioning along the dorsal–ventral axis in the OB. Thus, the dorsal–ventral arrangement of glomeruli is roughly determined by the locations of OSNs in the OE. Axonal projection along the dorsal–ventral axis is determined by axon guidance molecules such as Nrp2, Sema3F, and Robo2 expressed in a graded manner in the OE. OSN, Olfactory sensory neuron; OE, olfactory epithelium; OB, olfactory bulb; OR, odorant receptor; D zone, dorsal zone; V zone, ventral zone.

Figure 2.

Functional connectivity in the Drosophila antennal lobe. (A) False-colored scanning electron micrograph image of a Drosophila head illustrating the major olfactory (antenna) and gustatory (proboscis) organs (photo: Jürgen Berger, Max Planck Institute for Developmental Biology, Tübingen, Germany). (B) Cross section of adult antenna hybridized with an in situ probe to reveal expression of Or22a mRNA. (C) Projection of Or22a-expressing axons to the DM2 glomerulus in the antennal lobe, as traced with n-synaptobrevin:GFP (green). Neuropil is counterstained with nc82 (red). (D) Connectivity map of the adult fly antennal lobe, with glomeruli color-coded according to OSN type at the periphery. The position of the Or22a glomerulus is marked by the arrow in panels (C,D). The antennal lobe is represented as four slices arrayed from anterior (A) to posterior (P), with glomerular position depth-coded such that white glomeruli are superficial, gray glomeruli intermediate, and black glomeruli deep.

Figure 3.

Olfactory sensory neuron projections along the anterior–posterior axis in the mouse olfactory system. Each OR is thought to generate a unique level of cAMP signaling, which is converted to relative expression levels of axon guidance molecules such as Nrp1 and Sema3A via cAMP-dependent protein kinase A (PKA) and cAMP response element binding protein (CREB). An axon guidance receptor, Nrp1, and its repulsive ligand, Sema3A, are expressed in a complementary manner in OSNs and regulate pretarget sorting of axons. This axon sorting mechanism may be important to establish the topographic order in the OB based on the relative expression levels of guidance molecules expressed by axons. Once OSN axons are sorted, they need to be oriented along the correct axis before projecting onto the OB. This probably requires an intermediate cue, possibly encoded by Sema3A derived from the target or along the pathway between the OE and OB. A, anterior; P, posterior.

Figure 4.

Activity-dependent local axon sorting to form a discrete map on the mouse olfactory bulb. Although OR/cAMP signals regulate coarse targeting of OSN axons along the A–P axis at an earlier stage of patterning, neuronal activity generated by OR/cAMP signals regulates local axon sorting at a later stage. This may indicate that cAMP signals are generated by different mechanisms in earlier and later stages (reviewed in Imai and Sakano 2008). Levels of neuronal activity determine different sets of axon guidance and adhesion molecules, including Kirrel2/Kirrel3, ephrin-A/EphA, and BIG2. Expression levels of these molecules are affected by nares occlusion, although those of Nrp1/Sema3A are not. Kirrel2/Kirrel3 mediates local fasciculation of like axons via homophilic adhesion activities, whereas ephrin-A/EphA is thought to segregate heterotypic axons via contact repulsion. BIG2 is involved in heterophilic adhesion. (CNG) cyclic nucleotide gated channel, (ACIII) adenylyl cyclase III.

Figure 5.

Molecular determinants of neuronal identity and glomerular targeting in the Drosophila antennal lobe. (A), Notch signaling specifies cell fate of OSNs housed in the same sensillum. Three arbitrary sensilla (1–3) housing either 2 or 3 OSNs are depicted with the corresponding axonal targets of the individual OSNs. Although Notch^ON and Notch^OFF cells are adjacent in a given antennal sensillum, their targets are broadly dispersed in the antennal lobe (Endo et al. 2007). (B), Schematic of developmental events and pathways patterning the fly olfactory system. In early pupal stages PNs have already targeted dendrites to appropriate positions where future glomeruli will form, whereas OSN axons have only reached the edge of the antennal lobe. In midpupation, some OSN axons begin to enter the antennal lobe and target the appropriate glomerular region. Late in pupal life, all OSNs have arrived and synaptic matching refines the connections of OSN axons and PN dendrites. The genes known to be involved in each of these steps are indicated and discussed in the text.