The loss of scents: do defects in olfactory sensory neuron development underlie human disease?

The olfactory system is a fascinating and beguiling sensory system: olfactory sensory neurons detect odors underlying behaviors essential for mate choice, food selection, and escape from predators, among others. These sensory neurons are unique in that they have dendrites contacting the outside world, yet their first synapse lies in the central nervous system. The information entering the central nervous system is used to create odor memories that play a profound role in recognition of individuals, places, and appropriate foods. Here, the structure of the olfactory epithelium is given as an overview to discuss the origin of the olfactory placode, the plasticity of the olfactory sensory neurons, and finally the origins of the gonadotropin-releasing hormone neuroendocrine cells. For the purposes of this review, the development of the peripheral sensory system will be analyzed, incorporating recently published studies highlighting the potential novelties in development mechanisms. Specifically, an emerging model where the olfactory epithelium and olfactory bulb develop simultaneously from a continuous neurectoderm patterned at the end of gastrulation, and the multiple origins of the gonadotropin-releasing hormone neuroendocrine cells associated with the olfactory sensory system development will be presented. Advances in the understanding of the basic mechanisms underlying olfactory sensory system development allows for a more thorough understanding of the potential causes of human disease.

Comparative morphometry of the olfactory bulb, tract and stria in the human, dog and goat / Morfometría comparada del bulbo, tracto y estría olfatoria en el humano, perro y cabra

Morphometric parameters of olfactory brain components show species-dependent variations. However, the association of these parameters with olfactory function vis-à-vis ecological and evolutionary behaviors is poorly understood. In this study, a morphometric analysis of the olfactory bulb, tract and stria was carried out in three ecologically diverse animals comprising humans (primate), dogs (carnivore) and goats (herbivore) to elucidate differences in morphometry in relation to olfactory function. Using formalin-fixed brains, volumes and linear measurements of the olfactory structures were determined and correlated with those of cerebrum and the whole brain. The volume of the olfactory bulb was greatest in dogs, followed by goats and humans and constituted 0.31 percent, 0.18 percent and 0.01 percent, respectively, of the brain volume. Similarly, the ratio of volume of the bulb, tract and stria to that of brain was 1.95 percent in the dog, 0.77 percent in the goat and 0.03 percent in the human. The width of the bulb was greatest (p< 0.05) in dogs (10.80 +/- 1.64mm) compared to goats (8.25 +/- 0.96mm) and humans (5.50 +/- 0.71mm), and accounted for a hemisphere breadth of 42.91 percent, 29.73 percent and 8.94 percent respectively. Interestingly though, the total length of the olfactory bulb, tract and striae increased in the order of goat (34.5 +/- 1.30mm), human (36.25 +/- 1.70mm) and dog (48.20 +/- 1.92mm), and constituted 21.47 percent, 51.87 percent and 72.30 percent, respectively, of the hemisphere length. These results suggest that the morphometric adaptations of the olfactory components to olfactory function decline from the dog, to goat, to human, and this may be indicative of the varied olfactory functional needs in regard to the ecological diversity of these species.

Los parámetros morfométricos de los componentes del cerebro olfativo presentan variaciones que dependen de las especies. Sin embargo, la asociación de estos parámetros con la función olfativa vis-à-vis los comportamientos ecológicos y evolutivos es poco conocida. En este estudio se llevó a cabo un análisis morfométrico del bulbo, tracto y estría olfatoria en tres animales de diversidad ecológica que abarcan los seres humanos (primates), perros (carnívoros) y cabras (herbívoros) para dilucidar las diferencias en la morfometría en relación con la función olfatoria. El uso de cerebros fijados en formalina, los volúmenes y las medidas lineales de las estructuras olfativas se determinaron y se correlacionaron con el cerebro. El volumen del bulbo olfatorio fue mayor en los perros, seguidos por cabras y seres humanos y constituyeron un 0,31 por ciento, 0,18 por ciento y 0,01 por ciento, respectivamente, del volumen del cerebro. Del mismo modo, la relación entre el volumen del bulbo, vías y estrías al del cerebro fue de 1,95 por ciento en el perro, un 0,77 por ciento en la cabra y 0,03 por ciento en el ser humano. El ancho del bulbo fue mayor (p <0,05) en los perros (10,80 +/- 1.64mm) en comparación con cabras (8,25 +/- 0.96mm) y humanos (5,50 +/- 0.71mm), y representó una total hemisférico de 42,91 por ciento, 29,73 por ciento y 8,94 por ciento respectivamente. Sin embargo, curiosamente la longitud total del bulbo olfatorio, del tracto y estrías aumentaron en la cabra (34,5 +/- 1,30 mm), en humanos (36,25 +/- 1.70mm) y en el perro (48,20 +/- 1,92mm), y constituyeron 21,47 por ciento, 51,87 por ciento y 72,30 por ciento, respectivamente, del largo del hemisferio. Estos resultados sugieren que las adaptaciones morfométricas de los componentes olfativos de la función olfativa se van reduciendo de perro a cabra y al hombre y esto puede ser indicativo de las variadas necesidades funcionales olfativas en lo que respecta a la diversidad ecológica de estas especies.

Developing a sense of scents: plasticity in olfactory placode formation.

The sense organs of the vertebrate head arise predominantly from sensory placodes. The sensory placodes have traditionally been grouped as structures that share common developmental and evolutionary characteristics. In attempts to build a coherent model for development of all placodes, the fascinating differences that make placodes unique are often overlooked. Here I review olfactory placode development with special attention to the origin and cell movements that generate the olfactory placode, the derivatives of this sensory placode, and the degree to which it shows plasticity during development. Next, through comparison with adenohypophyseal, and lens placodes I suggest we revise our thinking and terminology for these anterior placodes, specifically by: (1) referring to the peripheral olfactory sensory system as neural ectoderm because it expresses the same series of genes involved in neural differentiation and differentiates in tandem with the olfactory bulb, and (2) grouping the anterior placodes with their corresponding central nervous system structures and emphasizing patterning mechanisms shared between placodes and these targets. Sensory systems did not arise independent of the central nervous system; they are part of a functional unit composed of peripheral sensory structures and their targets. By expanding our analyses of sensory system development to also include cell movements, gene expression and morphological changes observed in this functional unit, we will better understand the evolution of sensory structures.

Induced peripheral sensitivity in the developing vertebrate olfactory system.

The high dimensionality and unpredictability of the chemical world makes it difficult for the olfactory system to anticipate relevant stimuli and construct neural filters accordingly. A developmental solution to this problem would be to alter the sensory surface according to environmental conditions so as to enhance sensitivity to molecules of particular relevance. Evidence for this has been obtained in the rabbit. By feeding pregnant does aromatic juniper berries, it could be shown that newborn, weanling and even adult animals demonstrate a preference for juniper odor without subsequent postnatal experience, and that this is associated with enhanced peripheral sensitivity for juniper odor as measured by electro-olfactogram (EOG). This is consistent with the report that in young salmon olfactory imprinting is associated with enhanced, odor-specific sensitivity of receptor cells as measured by patch clamp. The mechanisms underlying such changes are unknown, including the extent to which they are a particular feature of developing systems.

Expression of isoforms of the neural cell adhesion molecule (NCAM) and polysialic acid during the development of the Bufo arenarum olfactory system.

The neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily that promotes Ca(2+)-independent cell-cell adhesion, is expressed as various isoforms generated by alternative splicing. In this study, the expression of the 180 kDa isoform (180-NCAM), total NCAM (180, 140 and 120 kDa isoforms) and the polysialic acid moiety of NCAM (PSA) were analyzed during the development of the olfactory system of the toad Bufo arenarum using specific antibodies and immunofluorescence light microscopy. NCAM and PSA were not found in the ectodermal thickening corresponding to the olfactory placode at early larval stage (stage 17), but by stage 19, total NCAM, 180-NCAM and PSA were all expressed in the invaginating olfactory placode at the sites of cell-cell contact and in the differentiating olfactory epithelium. Later, NCAM isoforms and PSA were found also in the primary fibers of the olfactory nerve and in the olfactory bulb. However, the expression of 180-NCAM decreased near the end of larval development and was absent in post-metamorphic and adult animals. In contrast, total NCAM (representing 140 and/or 120 kDa isoforms) and PSA continued to be expressed in olfactory tissues of post-metamorphic and adult animals, consistent with the persistent neural plasticity of this tissue. Because 180-NCAM has been associated with non-proliferating neurons, its down-regulation in post-metamorphic and adult olfactory system may be associated with the regenerative capability and continuous cell turnover documented for this region in adult animals.

Expression of 9-O-acetylated gangliosides during development of the rat olfactory system.

The expression of 9-O-acetylated gangliosides recognized by the Jones monoclonal antibody (mAb) correlates with cell migration and axonal outgrowth in the developing rat nervous system. We studied the expression of these gangliosides during the development and maturation of the rat olfactory system. Beginning on embryonic day 13 (E13) the olfactory epithelium and the migratory mass were intensely stained with Jones mAb. However, though this immunoreactivity disappeared from the olfactory epithelium at E19, it remained in a few fascicles and some glomeruli of the newborn and adult olfactory bulbs. We concluded that the expression of 9-O-acetylated gangliosides by olfactory axons and/or migrating cells may facilitate axonal outgrowth during development and might be involved in the formation of new glomeruli in the mature olfactory bulb.