Neuroscience/Objectives/Lecture 31

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Chemical senses

Understand the anatomy of the pathway from olfactory receptors to regions of the brain.

Olfactory receptor neurons in the olfactory mucosa are lined with cilia that contain molecular olfactory receptors. They are embedded in an olfactory epithelium lined with mucus secreted by serous glands of Bowman. Other cells of the olfactory epithelium are the basal and sustentacular (supporting) cells. The entire apparatus is called the nasal mucosa.

Because olfactory receptors are exposed to the environment, they suffer constant damage and must be protected via three mechanisms:

• warming and moistening of incoming air by respiratory epithelium
• immunoglobulins in the mucus secreted by the nasal mucosa
• olfactory neurons are constantly being replaced via the basal cells (complete turnover takes 6-8 weeks in rats)

Bipolar olfactory receptor neurons send unmyelinated axons through the cribiform plate (forming CN I) to terminate on apical dendrites of mitral cells within glomeruli of the olfactory bulb. Olfactory receptor neurons expressing distinct receptor types project bilaterally to symmetric glomeruli within the olfactory bulb. There is a high degree of convergence, with each mitral cell being innervated by perhaps 1,000 olfactory receptor neurons. This allows the detection of even very faint odors. In addition to the axons and dendrites of olfactory receptor neurons and mitral cells, respectively, the glomerulus also contains synapses with tuft cells and periglomerular cells, whose functions are unclear.

Axons of mitral cells project along the olfactory tract and terminate largely in the piriform cortex, olfactory tubercle, amygdala, and parts of the entorhinal cortex. Hence the olfactory system is intimately related to the limbic system. Olfactory axons also project to the thalamus, hypothalamus, orbitofrontal cortex, and indirectly to the hippocampus. The orbitofrontal cortex and thalamus have bidirectional connections serving to integrate food and drink stimuli and formulate goals, plans, and intentions.

Describe olfactory perception, including thresholds and types of stimuli.

Olfactory perception begins at the olfactory receptor neuron, which expresses a subset of odorant receptors. Humans are estimated to express 200–1,000 odorant receptors, each of which is a G protein-coupled receptor with seven transmembrane domains. Humans can discriminate between an estimated 10,000 distinct odors.

Because of the convergence between olfactory receptor neurons and olfactory glomeruli, the olfactory system is very sensitive to low odorant concentrations. The olfactory system also avoids activating in response to noise so that spontaneous changes in membrane potential, for example, do not result in the inappropriate perception of an odorant. This is achieved by olfactory neurons having high activation thresholds; namely, many cAMP-gated ion channels (discussed later) must be opened in order to trigger an action potential.

Discuss the transduction mechanisms of olfactory receptors.

Transduction pathway:

1. Odorant binds to G protein-coupled odorant receptor
2. Olfactory-specific G protein activates olfactory-specific adenylyl cyclase → ↑cAMP
3. cAMP opens Na⁺ and Ca²⁺ channels that depolarize the neuron
   • These channels are blocked at rest by high [Ca²⁺] and [Mg²⁺] present in the olfactory mucus
   • Several channels must be opened to overcome this voltage-dependent blockade
   • The result is that neurons fire only in the presence of odorants, thereby reducing noise in the system
4. Ca²⁺-activated Cl^- channels further depolarize the neuron
5. Odorant concentration is encoded in the frequency, response latency, and duration of neuronal firing.

Sustained stimulation of the olfactory receptor causes adaptation:

1. Chronic stimulation results in elevated Ca²⁺, which binds to greater amounts of calmodulin
2. Ca²⁺-calmodulin decreases the sensitivity of cAMP-gated channels and increases the rate at which Ca²⁺ is pumped out of the neuron by the Na⁺/Ca²⁺ exchanger, reducing the rate at which olfactory neurons fire action potentials.

Understand the anatomy of the pathway from taste cells to regions of the brain.

The tongue, soft palate, pharynx, and upper esophagus contain taste buds, which are clusters of taste cells that synapse with primary sensory axons in cranial nerves VII, IX, and X. These nerves carry taste information to the gustatory nucleus, the rostral portion of the nucleus of the solitary tract (NTS), which is located in the medulla. This nucleus also receives afferents from the part of CN X controlling gastric motility and is therefore the first point of interaction between gustatory and visceral stimuli.

The gustatory nucleus projects via the ventral posteromedial nucleus of the thalamus to the insula and frontal cortex. A parallel pathway carries input from the nucleus to the hypothalamus and amygdala.

Describe taste buds, taste receptors, and taste transduction.

Humans have 4,000 taste buds, each with 30–100 taste cells and some basal cells. About 3,000 taste buds are on the dorsal surface of the tongue embedded in the circumvallate papillae.

Taste cells contain apical microvilli, themselves containing taste receptors. At their basal surface, these cells synapse with axons of cranial nerves VII, IX, and X. The apical surfaces of taste cells within a taste bud are clustered in a small opening, the taste pore. Taste cells have a lifetime of about two weeks and are regenerated from the basal cells.

Threshold concentrations for needed substances (eg, salt) are in the mM range, while potentially noxious substances have thresholds in the µM range. In addition to bitterness, sweetness, and other basic tastes, the gustatory system includes umami (sensitive to free glutamate), astringency, pungency, fat, starch, metallic tastes, and others. All regions of the tongue can sense all types of taste, although some tastes are perceived better by specific regions. Stimulation of the tip of the tongue (mostly sensitive to sweetness) enhances feeding behavior, while stimulation of the back (mostly sensitive to bitterness) depress feeding behavior.

The transduction mechanisms of taste depend upon ionotropic and metabotropic receptors. Ionotropic receptors allow for the sensation of ions such as Na⁺. Activated metabotropic receptors initiate second messenger pathways that elevate intracellular Ca²⁺ and trigger the release of serotonin-containing vesicles from the taste cell.

Like olfactory receptor neurons, taste cells adapt to persistent stimuli. This is achieved by the active removal of Ca²⁺ from the taste cell, decreasing the frequency of firing.

The receptor for salt is a sodium channel capable of transmitting protons (responsible for sour taste) as well. The addition of acid (eg, lemon juice) to food allows protons to compete with sodium for the sodium channel, possibly explaining why acids decrease the perceived saltiness of a meal.

The mechanism of gustatory coding (ie, how a food is perceived as sweet, salty, etc.) is a point of controversy. The labeled line hypothesis posits that a single neuron is necessary and sufficient to perceive each specific taste. One of the basic tastes will evoke the greatest number of action potentials in a given neuron, and this neuron's activity will trigger the higher order perception of that taste. Simple tastes are thought to be processed using the labeled line model.

Complex foods comprising multiple simple tastes are thought to be processed using the across-neuron model. In this model, taste sensations are synthesized from the integrated activity of several neurons. The pattern of activity across all of neurons determines how the taste is perceived in this model. For example, the taste of sugar is computed from the response of all 40 taste cells.

The selectivity of neurons for particular tastes generally decreases from taste buds, to the solitary nucleus, to the thalamus, and to the gustatory cortex. Neurons in the gustatory cortex also respond to thermal, mechanical, olfactory, and visual stimuli pertaining to food.

Describe the basic anatomy of the trigeminal chemoreception system.

The trigeminal chemoreception system is analogous to the spinal nociceptive system except that it involves the face. The system is composed of nociceptive neurons and their axons in the cranial nerves V, IX, and X. These fibers contain irritant receptors on the face, scalp, cornea, and oral and nasal cavities. Information from these irritant receptors is relayed via the ophthalmic, maxillary, and mandibular branches of the trigeminal nerve, and is carried to second-order neurons of the trigeminal nuclei. These neurons project to the ventral posteromedial nucleus of the thalamus and thence to the somatosensory cortex and other cortical areas.

Thresholds for perceiving a substance as an irritant are much (perhaps 100x) higher than they are for the olfactory and gustatory systems. This explains why low concentrations of NaCl are perceived as salty, but 1.0 M NaCl is an irritant.

Little is known about the mechanisms of signal transduction in the trigeminal system. However, they are likely not shared with the mechanisms employed by the olfactory and gustatory systems.

The trigeminal system mediates a variety of responses, including vasodilation, tearing, nasal secretion, sweating, decreased respiratory rate, and bronchoconstriction. For example, eating a hot pepper (which contains capsaicin) results in tearing, salivation, and sweating in an attempt to dilute the stimulus.