CHAPTER 6: OLFACTION, TASTE, AUDITION, AND SOMATOSENSATION

Odorant detection by a given olfactory receptor neuron could be monitored (at least in theory) by:

(a) an increase in internal cAMP.

(b) an increase in internal Ca2+.

(c) an increase in internal Na+.

(d) a decrease in internal Cl-.

(e) All of the above

(e)

Odorant binding to a G-coupled-receptor activates Gaolf, which activates ACIII, converting ATP to cAMP. cAMP binding causes a cyclic nucleotide-gated channel to open, allowing the influx of Ca2+ and Na+. Ca2+ opens a channel that allows efflux of Cl-, further depolarizing the ORN.

Mechanisms for termination of olfactory responses in ORNs include:

(a) inhibition of the CNG channel by Ca2+/calmodulin.

(b) inhibition of the phosphodiesterase PDE1c by Ca2+/calmodulin.

(c) conversion of ATP to cAMP.

(d) activation of ACIII by CaMKII.

(e) All of the above

(a)

Ca2+/Calmodulin binds directly to the CNG and inhibits it, stopping the influx of cations. It also activates the phosphodiesterase PDE1c, which in turn hydrolyzes cAMP to AMP. CaMKII phosphorylates ACIII, which inactivates it and prevents conversion of additional ATP to cAMP.

Olfactory GPCR genes:

(a) include sequences encoding amino acids that are highly conserved in mammals.

(b) include sequences encoding amino acids that are highly variable between gene family members to permit binding to diverse odorants.

(c) probably underwent many duplications under selection pressure in rodents.

(d) accumulate more nonsense mutations in species that rely less heavily on smell.

(e) All of the above

(e)

There are many olfactory GPCR genes that share a common structure and highly conserved amino acid sequences but also have highly variable regions that would allow them to bind to different odor molecules. There are over a thousand functional OR genes in mice and rats but only 388 in humans, who do not rely as heavily on smell.

Each glomerulus in the mammalian olfactory bulb:

(a) receives information from the binding of a single type of odorant.

(b) receives information from the binding of a single type of olfactory receptor.

(c) is the site of convergence of the axons of ORNs expressing the same olfactory receptor.

(d) b and c

(e) a, b, and c

(d)

Each ORN expresses one olfactory receptor type that may be capable of detecting many different odorants. The axons of ORNs expressing the same receptor type converge at two glomeruli in the olfactory bulb.

What experiments support a model in which mammalian olfactory GPCRs are expressed specifically in ORNs that project to a particular glomerulus in the olfactory bulb?

ORs are expressed specifically by cells in the nasal epithelia that project to a particular glomerulus in the olfactory bulb, based on in situ hybridization using a probe complementary to the mRNA sequence and OR knock-ins of a tau-β-galactosidase fusion protein.

ORNs expressing the same odorant receptor:

(a) are spatially clustered in the nasal epithelium.

(b) are distributed randomly within one of four zones in the nasal epithelium.

(c) are distributed randomly throughout the entire nasal epithelium.

(d) are distributed randomly throughout the olfactory bulb.

(e) None of the above

(b)

ORNs expressing the same odorant receptor are distributed within one of four zones in the nasal epithelium, but their axons converge to the same glomeruli in the antennal lobe.

Which spatial map in the brain does not correspond to spatial properties of the stimulus?

(a) Visual map in tectum/superior colliculus

(b) Primary somatosensory cortex

(c) Primary motor cortex

(d) Olfactory map in olfactory bulb

(e) Auditory map in inferior colliculus

(d)

Although there is an olfactory map in the brain, it corresponds to the chemical nature of odorants detected, not to space in the external world

Which of the following statements is false?

(a) Each ORN innervates only one or two glomeruli in the olfactory bulb.

(b) Each mitral cell innervates only one or two glomeruli in the olfactory bulb.

(c) ORNs and mitral cells are excitatory.

(d) Periglomerular cells and granule cells are inhibitory.

(e) None of the above

(b)

Mitral cells have apical dendrites innervating a single glomerulus but also secondary dendrites that contact inhibitory granule cells, allowing lateral inhibition.

In the visual system, horizontal cells are excited by photoreceptor cells and in turn inhibit both the photoreceptor cells that excited them and nearby bipolar cells. The olfactory equivalent of the horizontal cell is the:

(a) periglomerular cell.

(b) granule cell.

(c) mitral cell.

(d) ORN.

(e) amacrine cell.

(a)

Periglomerular cells are also excited by primary sensory neurons (ORNs) and in turn inhibit both the ORNs that excited them and nearby mitral cells.

Example of dendrodentritic synapses include all of the following except:

(a) granule cells and mitral cells.

(b) periglomerular cells and mitral cells.

(c) photoreceptor cells and bipolar cells.

(d) horizontal cells and bipolar cells.

(e) amacrine cells and bipolar cells.

(c)

Granule cells, periglomerular cells, horizontal cells, and amacrine cells both receive and transmit information via their dendrites. Photoreceptor cells and bipolar cells only form canonical excitatory axo-dendritic synapses.

All sensory modalities are relayed to the cortex through the thalamus except for the:

(a) visual system.

(b) auditory system.

(c) somatosensory system.

(d) olfactory system.

(e) gustatory system.

(d)

Mitral and tufted cells of the olfactory system project directly to the cortex. All other sensory systems use (but are not necessarily limited to) a thalamocortical pathway.

Olfactory information has a discernable organization in all of the following structures except for the:

(a) olfactory bulb.

(b) piriform cortex.

(c) cortical amygdala.

(d) accessory olfactory bulb.

(e) None of the above

(b)

In contrast to the other structures, individual cortical neurons activated by specific odorants appear to be broadly distributed across the pyriform cortex, with no discernable spatial pattern.

It is very likely that humans use the main olfactory system for pheromone detection, given that:

(a) the TRPC2 gene has become a pseudogene in humans.

(b) the V2R genes have become pseudogenes in humans.

(c) the vomeronasal organ appears only transiently during human development.

(d) female humans' menstrual cycles can be influenced by compounds extracted from the armpits of donor females.

(e) All of the above

(e)

Although humans appear to have lost the accessory olfactory system in their evolutionary history, we still appear to detect some pheromones, most likely via the main olfactory system.

C. elegans avoid particular odors because these odorants:

(a) are inherently aversive chemicals.

(b) activate particular receptors that initiate a signal transduction cascade signifying aversion.

(c) activate particular receptors that are expressed by specific neurons that mediate avoidance.

(d) inhibit particular receptors that are expressed by specific neurons that mediate attraction.

(e) None of the above

(c)

Transgenic experiments in which receptors for attractive odors are expressed in the neurons that normally mediate avoidance demonstrate that the responses of these sensory neurons determine the behavioral output

Fill in each of the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.The C. elegans AWC olfactory circuit has much in common with vertebrate rod and cone circuits. Light _____________ cones, inhibiting _____________ release. OFF bipolar cells with _____________ glutamate receptors are hyperpolarized, while ON bipolar cells with _____________ glutamate receptors are depolarized. Similarly, odorant binding _____________ AWC, inhibiting glutamate release. AIB expresses a(n) _____________ glutamate receptor and is hyperpolarized. AIY expresses a glutamate-gated _____________ channel and is depolarized. In both cases, parallel pathways serve to enhance contrast between the presence and absence of the stimulus.

acetylcholine , hyperpolarizes, calcium, ionotropic, chloride, mechanosensitive, depolarizes, metabotropic, and glutamate sodium

The C. elegans AWC olfactory circuit has much in common with vertebrate rod and cone circuits. Light hyperpolarizes cones, inhibiting glutamate release. OFF bipolar cells with ionotropic glutamate receptors are hyperpolarized, while ON bipolar cells with metabotropic glutamate receptors are depolarized. Similarly, odorant binding hyperpolarizes AWC, inhibiting glutamate release. AIB expresses an ionotropic glutamate receptor and is hyperpolarized. AIY expresses a glutamate-gated chloride channel and is depolarized. In both cases, parallel pathways serve to enhance contrast between the presence and absence of the stimulus.

How does the insect olfactory circuit resemble the vertebrate olfactory circuit?

The insect and vertebrate olfactory circuits share many similarities in organization, although the fly olfactory system is much simpler numerically, making it a useful model. Most sensory neurons express a single odorant receptor, and ORNs expressing the same receptor project their axons to the same glomeruli in the primary olfactory center. Most relay interneurons directly contact a single type of ORN in the primary olfactory center. However, local inhibitory interneurons also influence the activity of these relay interneurons.

Which of the following is not true of the transformation of odorant coding between ORNs and projection neurons in the fly?

(a) In each glomerulus, a small number of ORNs form synapses with a large number of target PNs.

(b) PNs projecting to the same glomerulus form electrical synapses with each other to synchronize their activity.

(c) The synapses between ORNs and PNs exhibit short-term depression, leading to circuit-level olfactory adaptation.

(d) Local interneurons mediate presynaptic inhibition of ORN neurotransmitter release, leading to circuit-level olfactory adaptation.

(e) Population-level PN responses permit higher discriminatory power than population-level ORN responses.

(a) A large number of ORNs form synapses with a small number of target PNs, allowing individual PNs to pool information from the combined activity of many ORNs.

Several experiments suggest that the binding of carbon dioxide to its specific receptor, Gr21a, in a particular subset of ORNs is sufficient to mediate avoidance behavior in flies, much like activation of the AWB neurons in C. elegans. Briefly describe a novel experiment to confirm that activation of Gr21a-expressing neurons is sufficient for odorant avoidance in flies.

Expression of a different olfactory receptor using the Gr21a promoter and exposure to the appropriate, normally neutral, odorant known to bind to that receptor should cause flies to avoid that odorant.

In the third order insect brain structure called the lateral horn, olfactory inputs appear to be organized according to:

(a) similarity of chemical structure.

(b) spatial location in the external world.

(c) biological relevance (for example, food vs. reproduction).

(d) All of the above

(e) None of the above

(c)

Projection neurons activated by fruit odors vs. pheromones target specific regions of the lateral horn.

Follow-up experiments to those in adult flies were performed in Drosophila larvae, which have even smaller and simpler olfactory systems. Which of the following reported observations was not consistent with conclusions derived from studies of the adult olfactory system?

(a) Each ORN expresses a single type of olfactory receptor.

(b) Each ORN axon typically innervates a single glomerulus in the antennal lobe.

(c) Each projection neuron's dendrites typically innervates a single glomerulus in the antennal lobe.

(d) Each projection neuron typically connects one specific glomerulus in the antennal lobe with one stereotyped substructure in the mushroom body dendritic field.

(e) Each intrinsic mushroom body neuron innervates several glomeruli in the mushroom body calyx, apparently randomly.

(d)

Larval studies revealed that PN axon arborization in the mushroom body was highly stereotyped, in contrast to predictions from axon tracing studies in the adult brain.

The Asian small-clawed otter, which is closely related to omnivorous dogs and bears, has a nonfunctional T1R2 receptor gene. What does this information predict about the food preferences of this species?

T1R2 receptors detect sugars, and felines and several other obligate carnivores have a T1R2 pseudogene and show no preference for sweetness. The Asian small-clawed otter is most likely a carnivore rather than an omnivore

Mammalian gustatory systems have evolved to avoid even trace amounts of a wide variety of toxic alkaloids. What key features of our taste systems underlie this adaptive sensitivity?

Other organisms (particularly plants) have evolved many different toxic compounds that mammals are able to perceive and to avoid as bitter. There are many different T2R gene products, each of which has high affinity for its dedicated chemical compound, allowing recognition even at low concentrations. Multiple T2R genes (and not T1R genes) are co-expressed in specific taste cells, allowing many different compounds to be registered as bitter and to promote avoidance.

Which of the following statements is not true of both olfaction in C. elegans and taste in mammals?

(a) Each sensory neuron expresses multiple types of receptor.

(b) Sensory neuron activity reflects the biological significance of the odorant.

(c) A large number of chemical compounds can be discriminated from each other.

(d) All of the above

(e) None of the above

(c)

Each sensory neuron expresses multiple types of receptor, for example for various compounds perceived as bitter/aversive. Binding to any of these compounds elicits a similar response in neuronal activity and behavior (attraction vs. avoidance) without the need for further processing. However, chemosensory stimuli activating different receptors of the same neuron cannot easily be discriminated.

Activity in the sensory neurons that respond to a high concentration of salt in food:

(a) mediates attraction.

(b) can be inhibited by amiloride.

(c) responds only to sodium chloride.

(d) can also activate the bitter and sour tasting systems.

(e) All of the above

(d)

An amiloride-insensitive salty taste system responds to high concentrations of NaCl and other salts with aversion by recruiting the bitter and sour tasting systems.

All of the following are necessary for glutamate release by hair cells except:

(a) Ca2+ entry.

(b) K+ entry.

(c) a 2nd messenger.

(d) a stretch-sensitive mechanotransduction channel.

(e) Ca2+-dependent cell adhesion molecules.

(c)

Unlike vision and olfaction, audition does not depend on a 2nd messenger. Instead, a stretch-sensitive K+ ion channel opens in response to movement of the tip links, which are composed of Ca2+-dependent cell adhesion molecules. This depolarization promotes Ca2+ entry and glutamate release.

Sound intensity is encoded by:

(a) the position of an activated hair cell along the basilar membrane of the cochlea.

(b) the firing rate of downstream spiral ganglion neurons.

(c) the position of the termination of a specific spiral ganglion neuron on the hair cell.

(d) a and b

(e) b and c

(e)

The position of the activated hair cell encodes pitch, while the firing rate and position-dependent sensitivity of downstream spiral ganglion neurons encode intensity.

Frequency selectivity of the inner hair cells is greatly enhanced by:

(a) force generated by the opening of the mechanotransduction channel in inner hair cells.

(b) force generated by the opening of the mechanotransduction channel in outer hair cells.

(c) myosin motors at the tips of the stereocilia.

(d) voltage-dependent changes in length of the outer hair cells.

(e) All of the above

(a)

Outer hair cell motility enhances the frequency selectivity of inner hair cells. This involves (1) myosin-dependent outer hair bundle motility from force generation due to opening of the mechanotransduction channel and (2) voltage-dependent electromotility (shape changes in the outer hair cells), which has been shown to require prestin, a putative chloride channel.

The representation of sound frequency in a tonotopic map is established in the cochlea and maintained in the:

(a) superior olivary nucleus.

(b) inferior colliculus.

(c) thalamus.

(d) primary auditory cortex.

(e)All of the above

(e)

The tonotopic map originated in the cochlea is preserved at multiple levels in the brain, including the superior olivary nucleus, medial geniculate nucleus of the hypothalamus, and primary auditory cortex.

The first stage at which auditory inputs are integrated with those of other sensory modalities is the:

(a) dorsal cochlear nucleus.

(b) superior olivary nucleus.

(c) inferior colliculus.

(d) thalamus.

(e) primary auditory cortex.

(a)

The dorsal cochlear nucleus receives input from the auditory, somatosensory, and vestibular systems.

In both owls and mammals, interaural time and level differences permit sound localization via an auditory spatial map at the level of the:

(a) cochlear nuclei.

(b) nucleus laminaris/superior olivary nucleus.

(c) inferior colliculus.

(d) thalamus.

(e) primary auditory cortex.

(c)

While the NL/MSO neurons serve as coincidence detectors, their phase ambiguity must be resolved at the level of the inferior colliculus, which features an auditory spatial map.

The overrepresentation of sound frequencies between 60 and 62 Hz in the Doppler-shifted constant frequency area of a bat's auditory cortex reflects the importance of echolocation for discrimination of the:

(a) size of an object.

(b) relative velocity of an object.

(c) distance of an object.

(d) biological significance of an object (prey vs. non-prey).

(e)None of the above

(d)

Although echolocation provides information regarding the size, relative velocity, and distance of objects, the DSCF area is critical for the identification of flying insects by the frequencies of their wing beats

Indicate whether each of the following statements is true of the vestibular system, the auditory system, both, or neither.

A. Depolarization of hair cells activates voltage-gated Ca2+ channels and glutamate release.

B. Ganglion neurons fire action potentials at a high rate in the absence of sensory stimuli.

C. Force exerted on stereocilia opens mechanotransduction channels in hair bundles.

D. Hair cells are tuned to different frequencies according to their location.

A. both

B. vestibular system

C. both

D. auditory system

In both systems, forces on stereocilia open mechanotransduction channels in hair bundles, depolarizing hair cells and activating voltage-gated Ca2+ channels, resulting in glutamate release. Only hair cells in the auditory system are tuned to specific frequencies. The high rate of firing of ganglion cells at rest, which can be increased or decreased according to the direction of head movement, is unique to the vestibular system.

Which of the following is not true of nociceptive neurons?

(a) Their axon fibers have the fastest conduction speeds among somatosensory neurons.

(b) They typically have free nerve endings.

(c) They can be activated by heat.

(d) They can be activated by mechanical stimuli.

(e) They can be activated by specific chemical compounds.

(a)

While it may seem counterintuitive, nociceptive neurons have the two classes of axon fibers with the slowest conduction speeds. They typically have free nerve endings and can be activated by extreme temperatures, harsh mechanical stimuli, or specific chemical compounds such as capsaicin or substances released by the inflammatory response.

Piezo1 and Piezo2 were identified in an RNAi knockdown screen in a mouse neuroblastoma cell line. State whether each of the following experiments suggested that at least one Piezo was necessary, sufficient, or present in the right time and place to mediate touch mechanotransduction in vivo.

A. Misexpression of Piezo1 or Piezo2 in cells conferred mechanically induced inward current.

B. Purified Piezo1 formed an ion channel in artificial lipid bilayers.

C. Conditional knockout of Piezo2 in Merkel cells and adult sensory neurons abolished behavioral responses to low-force mechanical stimuli.

D. Piezo2 (but not Piezo1) was expressed in a subset of DRG neurons.

A. sufficient

B. sufficient

C. necessary

D. present in right time and place

Indicate whether each of the following statements is true of insects, vertebrates, both, or neither.

A. Piezo is a mechanosensitive ion channel.

B. Piezo is an innocuous touch sensor.

C. An ENaC channel is an innocuous touch sensor.

D. A TRP channel is an innocuous touch sensor.

A. both

B. vertebrates

C. neither

D. insects

Drosophila melanogaster Piezo is a mechanosensitive ion channel, but it mediates nociception (along with one of the ENaC channels), not innocuous touch as in vertebrates. The Drosophila TRP channel NompC is used to sense gentle touch, but TRP channels in vertebrates sense noxious temperatures and chemicals.

Which of the following would be expected to activate neurons expressing the TRP channel family member TRPV1?.

(a) Temperatures < 26°C

(b) Temperatures > 43°C

(c) Capsaicin

(d) a and b

(e) b and c

(e)

TRPV1 is responsive both to noxious heat and to capsaicin

If an experimenter were to express light-activated channelrhodopsin in a mouse using the Bhlhb5 promoter, what behavioral outcome would support the current model for responses to itchy vs. painful stimuli?

In the current model, Bhlhb5+ neurons inhibit the GRPR neurons that mediate the perception of itchiness and a scratching response, and the bacterial channelrhodopsin is activated by light. Targeted illumination should suppress scratching with the back foot.

Fill in each of the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.Touch sensory neurons synapse with target projection neurons of the ___________ horn of the spinal cord in the ___________ dorsal column pathway and send a branch up to the ___________ in the ___________ dorsal column pathway. Medullary target neurons cross the midline before ascending to the ___________. In addition, touch information from ___________ skin is relayed by distinct dorsal horn projection neurons to the ___________ cervical nucleus via the ___________ tract pathway.

amygdala, lateral, direct, medial, dorsal, medulla, glabrous, spinocervical, hairy, thalamus, indirectventral

Touch sensory neurons synapse with target projection neurons of the dorsal horn of the spinal cord in the indirect dorsal column pathway and send a branch up to the medulla (brainstem) in the direct dorsal column pathway. Medullary target neurons cross the midline before ascending to the thalamus. In addition, touch information from hairy skin is relayed by distinct dorsal horn projection neurons to the lateral cervical nucleus via the spinocervical tract pathway.

Sites of tissue damage or infection are more sensitive to heat because:

(a) there are no endogenous analgesics to inhibit nociceptive pathways.

(b) molecules produced by the inflammatory response also increase the sensitivity of TRP channels to sensory stimuli via a second messenger system.

(c) the neurons that modulate thermosensation are among the most easily injured or damaged.

(d) the enzymes that synthesize prostaglandin are temperature-sensitive.

(e) None of the above

(b)

Prostaglandin and bradykinin bind specific GPCRs on nociceptive neurons and activate second messenger systems that open TRP channels.

Opioids derived from the poppy, such as morphine:

(a) bind G-protein-coupled receptors that are responsive to endorphin and encephalin.

(b) act directly on peripheral sensory neurons.

(c) act directly on spinal cord neurons.

(d) act directly on neurons in the brainstem.

(e) All of the above

(e)

Opioids bind to GPCRs that are expressed in peripheral sensory neurons, spinal cord neurons, and neurons in the brainstem and are receptors for endogenous peptides such as endorphin and enkephalin.

Perceptual and electrophysiological experiments in humans and monkeys revealed that the threshold amplitude for perceptual detection of high-frequency repetitive mechanical stimuli:

(a) was significantly different between species.

(b) closely matched the lowest amplitude that activated Meissner corpuscles.

(c) closely matched the highest amplitude that activated Meissner corpuscles.

(d) closely matched the lowest amplitude that activated Pacinian corpuscles.

(e)closely matched the highest amplitude that activated Pacinian corpuscles.

(d)

The lower bound of the detection threshold for Pacinian corpuscles correlated very well with the perceptual threshold for both humans and monkeys.

In monkeys trained to report detection of a vibratory stimulus, activity in which part of the cortex most accurately predicted a behavioral response signifying perception ?

(a) Primary somatosensory cortex

(b) Secondary somatosensory cortex

(c) Premotor cortex

(d) Primary motor cortex

(e) None of the above

(c)

Activity of neurons in the medial premotor cortex (MPc) predicted behavioral response well above chance, in contrast to that in the primary somatosensory or motor cortices.

In insects, gustatory sensory neurons project from the proboscis and other structures to the subesophageal ganglion. Interestingly, insects have gustatory sensory neurons that mediate the recognition of water, which is necessary for animals to maintain osmotic homeostasis. Kristin Scott and colleagues have proposed that ppk28, a member of the Degenerin/Epithelial Sodium Channel family, is an osmosensitive ion channel involved in the cellular and behavioral response to water.

A. ppk28 is a predicted ion channel recovered from a microarray screen for genes expressed in the proboscis of wild-type flies but not Poxn-/- flies (which lack all taste neurons). How could you confirm experimentally that this gene was expressed in gustatory neurons?

B. The experimenters found that about two-thirds of ppk28-expressing neurons were also positive for a marker of water-sensing neurons in taste bristles. Expression of a genetically encoded calcium sensor in ppk28+ neurons using the GAL4/UAS system allows visual monitoring of depolarization. What response would you predict from these neurons upon the presentation of aqueous solutions of various concentrations?

C. How would you demonstrate that ppk28 was necessary for a cellular vs. behavioral response to water?

A. One could perform in situ hybridization and/or use the promoter region of the ppk28 gene to drive a reporter gene to detect endogenous gene expression in gustatory neurons and in their axons projecting to the subesophageal ganglion.

B. Robust activity is expected in response to water, with the strength of the response inversely correlated with the concentration of other compounds in the aqueous solution.

C. Generate a ppk28 null fly. Extracellular bristle recordings or genetically encoded calcium sensors should show a reduced or absent response to water in the gustatory sensory neurons of ppk28 null vs. wild-type flies. In addition, ppk28 null flies should imbibe less water than wild-type flies.