Olfaction and Taste

Figure 23-1. Sagittal magnetic resonance image of the hemisphere and nasal structures showing the general relationships of the olfactory bulb.

The receptors responsible for transduction of odor molecules are found in the olfactory mucosa. This portion of nasal mucosa is 1 to 2 cm² in size and is located in the roof of the nasal cavity on the inferior surface of the cribriform plate and along the nasal septum and medial wall of the superior turbinate (Fig. 23-2). The olfactory mucosa is composed of a superficial acellular layer of mucus that covers the olfactory epithelium and underlying lamina propria. The olfactory epithelium is differentiated from the adjacent pinkish respiratory epithelium by its faint yellowish color and greater thickness. In humans the transition between olfactory and respiratory epithelia is gradual.

Figure 23-2. Sagittal section through the human nasal cavity showing the relationship of the olfactory epithelium and bulb to the cribriform plate.

The olfactory epithelium is pseudostratified and contains three main cell types: olfactory receptor neurons, supporting cells (sustentacular cells), and basal cells (Fig. 23-3A, B). The small (5 µm) somata of bipolar olfactory receptor neurons are found in the basal two thirds of the epithelium. Each has a single thin apical dendrite and a basally located unmyelinated axon. The apical dendrite extends to the surface of the epithelium, where it terminates in a knob-like olfactory vesicle from which 10 to 30 nonmotile cilia arise and protrude into the overlying mucus layer (Fig. 23-3C, D). These olfactory cilia contain receptors for odorant molecules.

Figure 23-3. Schematic drawing of the olfactory epithelium (A). Light micrograph of the human olfactory epithelium and the underlying lamina propria (B). Scanning electron micrographs of the human olfactory epithelium showing its characteristic cell types (C) and the dendritic knob and cilia of a receptor neuron (D).(Photomicrographs courtesy of Dr. Richard M. Costanzo, Virginia Commonwealth University.)

The unmyelinated axon of an olfactory receptor neuron is about 0.2 µm in diameter, making it one of the smallest in the nervous system. These axons pass through the lamina propria and group together into bundles called olfactory fila, which collectively make up the olfactory nerve (cranial nerve I) (Fig. 23-3A). The olfactory fila pass through the cribriform plate to terminate in the olfactory bulb.

Olfactory receptor cells are true neurons because they originate embryologically from the central nervous system. Olfactory receptor cells undergo continuous turnover, with an average life span between 30 and 60 days. They are replaced by receptors arising from undifferentiated basal cells by mitotic division (Fig. 23-3A, C). Thus basal cells are stem cells that give rise to the receptor cells.

The supporting cells are columnar and extend from the lamina propria to the surface of the epithelium, where they end in short microvilli that extend into the overlying mucus (Fig. 23-3A, C, D). Nuclei of the sustentacular cells are found near the surface of the epithelium. These cells provide mechanical support for the olfactory receptor cells (Fig. 23-3B). In addition, they contribute secretions to the overlying mucus that may play a role in the binding or inactivation of odorant molecules.

A fourth and minor cell type, the microvillar cell, is found in the human olfactory epithelium (Fig. 23-3B). These cells have an apical process that projects into the mucus and a basal process that extends to the lamina propria. Although their function is unknown, they may be a second type of receptor neuron.

The lamina propria contains bundles of olfactory axons, blood vessels, fibrous tissue, and numerous Bowman glands (Fig. 23-3A). The serous secretions of the Bowman glands, combined with the secretions of the sustentacular cells, provide the mucus covering of the olfactory mucosa.

OLFACTORY TRANSDUCTION

Olfactory perception begins when volatile odor molecules are inhaled and contact the mucus layer that bathes the olfactory epithelium. This mucus is an aqueous solution of proteins and electrolytes. Odorants, particularly hydrophobic ones such as musk, cross the mucus by interacting with small, water-soluble proteins called odorant-binding proteins. These proteins are ubiquitous in the mucus layer.

After crossing the mucus, odor molecules bind to odorant receptors on the cilia of the olfactory receptor neurons, where transduction occurs (Fig. 23-4). The odorant receptors are membrane proteins belonging to a superfamily of G protein–coupled receptors. Binding of the odorant to one of as many as 1000 different types of odorant receptors leads to activation of a second messenger pathway involving an olfactory-specific G protein, which in turn activates adenyl cyclase to produce cyclic adenosine monophosphate (cAMP). The transient rise in ciliary cAMP opens a cyclic nucleotide–gated cation channel in the ciliary membrane, allowing cations to flow into the cell (Fig. 23-4). The flow of cations into the cell results in a gradual depolarization (generator potential) that travels down the dendrite to the soma of the olfactory receptor neuron. A sufficiently large depolarization initiates an action potential that travels along the axon to the olfactory bulb.

Figure 23-4. Pathways of olfaction transduction. Odorants are transported through the mucus by odorant-binding proteins. Binding of odorants to receptors on the olfactory cilia activates a second messenger pathway involving either cyclic AMP (cAMP) or inositol 1,4,5-trisphosphate (IP₃). Both pathways lead to the opening of membrane cation channels and depolarization of the olfactory receptor neuron. PIP₃, phosphatidylinositol 4,5-bisphosphate.

There is also evidence for another intracellular second messenger pathway in olfactory transduction. This pathway, involving inositol 1,4,5-trisphosphate (IP₃), is thought to act either separately or with the cAMP pathway. In this pathway, binding of odorant to the receptor activates a G protein that in turn activates phospholipase C to produce IP₃. The IP₃ opens a channel in the ciliary membrane that permits calcium to enter the cell (Fig. 23-4). Current research further supports a role for cyclic guanosine monophosphate and carbon monoxide in olfactory signal transduction.

Studies suggest that olfactory discrimination begins in the olfactory epithelium and that a “receptor map” is used to encode complex qualities of a given odor. Receptors, which are tuned to specific structural features of a stimulus, appear not only to be selectively expressed within subsets of the olfactory neuron population but also to exhibit spatial organization. In fact, findings indicate that individual olfactory neurons express only one type of odorant receptor and that specific subtypes of odorant receptors preferentially distribute within one of four bilaterally symmetric zones of the olfactory epithelium. Such specificity permits olfactory information to be patterned for additional processing in the olfactory bulb.

CENTRAL OLFACTORY PATHWAYS

Olfactory Bulb

The olfactory bulb, a forebrain structure, is located on the ventral surface of the frontal lobe in the olfactory sulcus and is attached to the rest of the brain by the olfactory tract. The olfactory tract is an inclusive structure that contains fibers of the lateral olfactory tract, cells of the anterior olfactory nucleus, and fibers of the anterior limb of the anterior commissure. The latter part of the olfactory tract is the route through which many centrifugal fibers reach the olfactory bulb (see Fig. 23-7).

The olfactory bulb consists of five well-defined layers of cells and fibers, which give it a laminated appearance. From superficial to deep, these are the olfactory nerve layer, glomerular layer, external plexiform layer, mitral cell layer, and granule cell layer (Fig. 23-5).

Figure 23-5. Schematic drawing of the olfactory bulb, showing the laminar organization, the major cell types, and the basic neuronal circuitry. Receptor neurons are shown in blue, interneurons in red, efferent neurons of the bulb in green, and centrifugal fibers in black.

The afferent projections from the olfactory epithelium form the olfactory nerve layer on the surface of the olfactory bulb. These axons terminate exclusively in structures called olfactory glomeruli, which are found in the glomerular layer of the bulb (Figs. 23-5 and 23-6). The axon of each olfactory sensory neuron synapses in only one glomerulus. Interestingly, the terminations of these axons are arranged such that neurons expressing the same receptor subtype target the same few glomeruli. This suggests that each glomerulus receives input from only one type of receptor.

Figure 23-6. Synaptic interaction between the principal cell types of the olfactory epithelium and bulb. Excitatory synapses (+) are shown in green and inhibitory ones (−) in red. The action of centrifugal axons in the glomerulus is not clearly established.

Glomeruli are the most prominent feature of the olfactory bulb. The core of an olfactory glomerulus is made up of the axons of olfactory receptor neurons, which branch and synapse on the bushy endings of the primary dendrites (apical dendrites) of mitral and tufted cells (Fig. 23-5). These two cells are functionally similar and together constitute the efferent neurons of the olfactory bulb. Adjacent to the glomerulus are small interneurons (juxtaglomerular cells), of which periglomerular cells are the principal type. This cell has short bushy dendrites that arborize extensively within a glomerulus and a short axon that distributes within a radius of about five glomeruli.

There is significant neural convergence at the level of the olfactory glomerulus; thousands of olfactory receptor neurons form excitatory (glutaminergic, carnosine) axodendritic synapses on mitral, tufted, and periglomerular cells (Fig. 23-6). The other major synaptic connections within the glomerulus are reciprocal and serial dendrodendritic synapses between mitral or tufted cells and periglomerular cells. It appears that the synapses of mitral and tufted cells onto periglomerular cells are excitatory (glutaminergic), whereas those of periglomerular cells onto mitral and tufted cells are inhibitory (GABAergic; GABA, for γ-aminobutyric acid).

The glomerular layer also receives input from other central nervous system areas via centrifugal afferents that use a wide variety of neurotransmitters and neuromodulators (Figs. 23-5 and 23-6). Noradrenergic centrifugal afferents from the locus ceruleus and serotonergic fibers from the raphe nuclei of the midbrain and rostral pons terminate in the glomeruli. Centrifugal fibers from the ipsilateral anterior olfactory nucleus and the diagonal band terminate in the periglomerular spaces, primarily on periglomerular cells. Excitatory amino acids, such as glutamate, are present in centrifugal fibers that arise in cortical structures.

The external plexiform layer is composed of the somata of tufted cells along with the primary and secondary dendrites (basal dendrites) of tufted and mitral cells and the apical dendrites of granule cells (Fig. 23-5). Within this layer, the apical dendrites of granule cells form reciprocal dendrodendritic GABAergic synapses with the secondary dendrites of tufted and mitral cells. These synapses modulate tufted and mitral cell output through lateral and feedback inhibition. Mitral and tufted cells, in turn, form excitatory (glutaminergic) synapses with granule cell dendrites (Fig. 23-6).

The mitral cell layer is a thin layer containing the large somata of mitral cells. In addition, the axons of tufted cells, granule cell processes, and centrifugal fibers traverse this layer (Fig. 23-5).

Internal to the mitral cell layer, the granular cell layer contains the cell bodies of granule cells, the principal interneuron of the olfactory bulb. This layer also contains primary and collateral axons of mitral and tufted cells and centrifugal afferents from the anterior olfactory nucleus, olfactory cortex, cells of the diagonal band, locus ceruleus, and raphe nucleus (Fig. 23-5). Granule cells lack axons, their only output being via dendrodendritic GABAergic synapses with mitral and tufted cells. In addition, granule cells receive numerous synaptic inputs from both mitral and tufted cell axon collaterals and centrifugal afferent fibers. Granule cells presumably modulate olfactory bulb activity via an inhibitory feedback loop that shuts down the activity of the mitral and tufted neurons.

Olfactory Bulb Projections

Axons of mitral and tufted cells emerge from the caudal portion of the olfactory bulb to form the lateral olfactory tract. Although glutamate is the major neurotransmitter of these efferent fibers, aspartate, dopamine, and substance P also are used. These fibers course caudally to terminate in areas on the ventral surface of the telencephalon, which are broadly defined as the olfactory cortex (Fig. 23-7). The principal areas making up the olfactory cortex are the anterior olfactory nucleus, olfactory tubercle, piriform cortex, anterior cortical amygdaloid nucleus, periamygdaloid cortex, and lateral entorhinal cortex. The olfactory cortex is an example of paleocortex, a phylogenetically older type of cortex that is less complex than the neocortex. Throughout most of its extent, the olfactory cortex has three cell layers, as opposed to the six layers characteristic of neocortex. A unique aspect of the olfactory system is that the olfactory bulb projects directly to the cortex. In other sensory systems, information reaches the cortex after a relay in the thalamus.

Figure 23-7. Major efferent projections of the olfactory bulb. Direct projections from the olfactory bulb are shown in blue, and indirect interbulbar connections via the anterior olfactory nucleus are depicted in red.

Lateral olfactory tract axons send collaterals to the anterior olfactory nucleus, to other areas of olfactory cortex, and to subcortical limbic structures. The major targets of the anterior olfactory nucleus are the olfactory bulbs bilaterally and the contralateral anterior olfactory nucleus (Figs. 23-7 and 23-8). The large numbers of interbulbar connections, via the anterior olfactory nucleus, suggest that interhemispheric processing of odors plays an important role in olfactory functions.

Figure 23-8. Major projections of the olfactory cortex.

Axons of the lateral olfactory tract course caudally in the form of the lateral olfactory stria to terminate in the olfactory tubercle and the piriform cortex (Fig. 23-7). The piriform cortex is a major component of the olfactory cortex. Fibers of the lateral olfactory tract also continue posteriorly to terminate in the anterior cortical amygdaloid nucleus, the periamygdaloid cortex (a part of the piriform cortex overlying the amygdala), and the lateral entorhinal cortex.

There is little evidence of a topographic projection from the olfactory bulb onto the various structures constituting the olfactory cortex. Mitral cells project to all areas of the olfactory cortex, whereas tufted cells terminate primarily in its anterior parts. However, each region of olfactory cortex is regarded as receiving input from all areas of the olfactory bulb.