Leaders in Pharmaceutical Business Intelligence (LPBI) Group

The structure of our visual and auditory system

Larry H. Bernstein, MD, FCAP, Curator

Leaders in Pharmaceutical Intelligence

Series E. 2; 5.8

Revised 9/30/2015

Torsten N. Wiesel (1921— )
President Emeritus
Vincent and Brooke Astor Professor Emeritus – Rockefeller Univerity
1981 Nobel Prize in Physiology or Medicine

The structure of our visual system, beginning at the eyes and ending at the primary visual cortex at the back of the brain, is a little like a maze, intricately constructed to send visual signals through myriad portals and passageways to reach just the right neurons at the end of the path. In the 1950s, H. Keffer Hartline, a member of The Rockefeller Institute for Medical Research, charted the first avenues of that maze when he revealed how the visual stimulus received by the retina is divided, altered and sharpened by the optic nerve network in order to send a more useful picture to the brain. Former Rockefeller president Torsten N. Wiesel, along with his colleague David H. Hubel, continued Dr. Hartline’s exploration at their Harvard Medical School laboratory by delving further back, into the brain, and described for the first time how the system develops innately, how experience shapes it further and how it analyzes visual signals. For this work, Drs. Wiesel and Hubel shared the 1981 Nobel Prize in Physiology or Medicine.

The complex array of stimuli in our visual field passes first through several distinct layers of cells known collectively as the retina. Next they are analyzed by the optic nerve and make their way to the lateral geniculate nucleus (LGN), the first visual processing center in the brain, located in the thalamus of each brain hemisphere. From the LGN, the signals are sent to the primary visual cortex, also known as the striate cortex. Working with cats and rhesus macaque monkeys, Drs. Wiesel and Hubel recorded the electrical impulses of cortical cells in response to various patterns flashed before the eyes. They coined the terms “simple” and “complex” for cells that respond to only one type of stimulus and those that respond to multiple and opposite stimuli.

To understand the differentiation, the scientists conducted a series of experiments to observe the brain’s response when one eye is kept closed for different periods of time. They discovered that animals with one eye closed for the first three months of life become blind in that eye. Examinations revealed no change in the eye itself or in the retina; the LGN cells devoted to that eye had shrunken but still responded to stimulation of the deprived eye as efficiently as those for the normal eye. The difference, they concluded, must therefore be in the striate cortex.

Awards: Nobel Prize in Physiology or Medicine, Louisa Gross Horwitz Prize, National Medal of Science for Biological Sciences

Swedish-born American neurobiologist Torsten N. Wiesel was raised at Beckomberga Hospital, the mental institute where his father was chief psychiatrist. He described himself as a lazy student until his late teens, before embarking on a career of research into the physiology of vision. Wiesel was awarded the Nobel Prize for Medicine in 1981, along with his long-time collaborator David H. Hubel, for mapping the visual or striate cortex, the posterior section of the cerebral cortex. Roger W. Sperry shared that year’s Nobel honors, for work conducted at CalTech. Wiesel also demonstrated the importance of early diagnosis of childhood visual problems.

When a reporter informed him he had won the Nobel Prize, Wiesel’s first response was, “Oh, no, I was afraid of that”, explaining that he feared the hubbub might prove a distraction from his work. In the 1990s he was President of Rockefeller University, and since 2000, he has been Secretary-General of the Human Frontier Science Program, a group which supports collaboration across different scientific fields. He also served more than a decade as Chair of the Human Rights Committee for the National Academy of Sciences.

In 2001, he was named to a high-level post at the National Institutes of Health, but his nomination was scuttled by then-Secretary of Health and Human Services Tommy Thompson, with the official explanation that he had “signed too many full-page letters in the New York Times critical of President Bush.” Wiesel responded, “I have not signed a statement against Bush, but nonetheless for some reason I am on the administration’s blacklist. Perhaps [it is because of] my human rights activities and being contrary in general.”

Structure and evolution of hearing

9.2015 The Scientist

Inner Ear Cartography

Scientists map the position of cells within the organ of Corti.  by Ruth Williams

Age-related hearing loss caused by damage to the sensory hair cells within the cochlea is extremely common, but studying the inner ear is tough. “It’s in the densest bone in the body, so you don’t have access,” says John Brigande of Oregon Health and Science University in Portland. Even if you can extract cells, he says, “there are so darn few of them.” Despite these technical difficulties, researchers have gleaned gene-expression information about different cell types within the organ of Corti—home to the sensory cells within the cochlea. But “it’s not only important to know what a cell expresses,” says Robert Durruthy-Durruthy, a postdoc in the Stanford University lab of Stefan Heller. “It’s also important to know where it can be found within a tissue.” To this end, Durruthy-Durruthy, Heller, and postdoc Jörg Waldhaus have derived a 2-D map of organ of Corti cells from neonatal mice. First, the team sorted all cell types across the medial-to-lateral axis (or width) of the organ based on marker gene expression. The approximately 900 sorted cells, representing nine cell types, were then each quantitatively analyzed for the expression of 192 selected genes. Computational analysis of these expression data then enabled reconstruction of the cells’ positions along the organ’s apical-to-basal (length) and medial-to-lateral axes. In principle, the technique, which harnesses gene-expression information to determine cells’ spatial organization, could be applied to generate 2-D maps of any complex tissue, says Durruthy-Durruthy. Within the mammalian cochlea, apical cells retain regenerative capacity for a few weeks after birth, but basal cells do not. “Spatial mapping allows us to get at the differences [between these cells],” says Brigande, and that could ultimately highlight possible ways to reinstate regeneration in the adult ear. (Cell Reports, 11:1385-99, 2015) To build a map of cells within the organ of Corti—where sound is translated to neural activity— scientists divide the cochlea in two. Each half of the organ of Corti is then broken up into its constituent cells, which comprise nine cell types (represented by the nine colors) spanning the organ’s medial-to-lateral axis.

FROM CELLS TO GENE-EXPRESSION: Each cell is analyzed for the expression of 192 selected genes. Based on the pattern of expression, a cell is given a position within the organ of Corti along both the basal-apical and the medial-lateral axes. Each column represents one of the nine cell types.

Human Hearing: A Primer

Semicircular canals of the vestibular system OSSICLES Ear canal Tympanic membrane (eardrum) When sound enters the ear canal, it vibrates the tympanic membrane, or eardrum. These vibrations are passed through the inner ear via three small bones called ossicles: the malleus, the incus, and the stapes. Finally, vibrations of the stapes stimulate the movement of a fluid called perilymph within the bony labyrinth of the inner ear.

Cochlea – How the human ear translates sound waves into nervous impulses.

Perilymph fills the both the vestibular and tympanic ducts of the cochlea. Between these two channels lies the cochlear duct, which is home to the organ of Corti. There, the soundinduced movement of perilymph in the cochlea is translated to an electrical signal that is sent to the brain for processing.

The organ of Corti sits on the basilar membrane, which separates the cochlear duct from the tympanic duct. As the basilar membrane vibrates in response to fluid movement, it pushes the organ along the tectorial membrane, which shifts laterally over the hair cells. This shift bends projections at the tips of the cells, called stereocilia, resulting in the generation of electrical signals.

The bending of the stereocilia results in the depolarization of the inner hair cell and initiates a nerve impulse through the spinal ganglion neuron at the base of the cell. A series of outer hair cells serves to mechanically amplify the vibrations that trigger the inner hair cells to fire. High-frequency sounds stimulate hair cells at the base of the cochlea, while low-frequency sounds stimulate hair cells at the apex.

Aural History -The form and function of the ears of modern land vertebrates cannot be understood without knowing how they evolved.

by Geoffrey A. Manley

Unlike eyes, which are generally instantly recognizable, ears differ greatly in their appearance throughout the animal kingdom. Some hearing structures may not be visible at all. For example, camouflaged in the barn owl’s facial ruff—a rim of short, brown feathers surrounding the bird’s white face—are clusters of stiff feathers that act as external ears on either side of its head. These feather structures funnel sound collected by two concave facial disks to the ear canal openings, increasing the bird’s hearing sensitivity by 20 decibels—approximately the difference between normal conversation and shouting.

Similar increases in sensitivity result from the large and often mobile external structures, or pinnae, of many mammals, such as cats and bats. Internally, the differences among hearing organs are even more dramatic.

Although fish can hear, only amphibians and true land vertebrates—including the aquatic species that descended from them, such as whales and pinnipeds—have dedicated hearing organs. In land vertebrates belonging to the group Amniota, including lizards, birds, and mammals, sound usually enters through an external canal and impinges on an eardrum that is connected through middle-ear bones to the inner ear. There, hundreds or thousands of sensory hair cells are spread along an elongated membrane that acts as a spectral analyzer, with the result that each local group of hair cells responds best to a certain range of pitches, or sound frequencies. The hair cells then feed this information into afferent nerve fibers that carry the information to the brain. (See “Hearing Primer” on page 34.)

Together, these hair cells and nerve fibers encode a wide range of sounds that enter the ear on that side of the head. Two ears complete the picture, allowing animals’ brains to localize the source of the sounds they hear by comparing the two inputs. Although it seems obvious that the ability to process nearby sounds would be enormously useful, modern amniote ears in fact arose quite late in evolutionary history, and to a large extent independently in different lineages. As a result, external, middle, and inner ears of various amniotes are characteristically different.1

Moreover, the early evolution of these dedicated auditoryorgans in land vertebrates led to the loss of the heavy otolithic membrane that overlies the hair-cell bundles of vestibular organs and is responsible for their slow responses. What remains is the watery macromolecular gel known as the tectorial membrane, which assures that local groups of hair cells move synchronously, resulting in greater sensitivity.

Good high-frequency hearing did not exist from the start, however. For a period of at least 50 million years after amniotes arose, the three main lineages were most likely quite hard of hearing. They had not yet evolved any mechanism for absorbing sound energy from air; they lacked the middle ear and eardrum that are vital for the function of modern hearing organs. As such, ancestral amniotes most likely perceived only sounds of relatively low frequency and high amplitude that reached the inner ear via the limbs or, if the skull were rested on the ground, through the tissues of the head. It is unclear what kind of stimuli could have existed that would have led to the retention of such hearing organs for such a long time.

The magnificent middle ear

During the Triassic period, some 250 to 200 million years ago, a truly remarkable thing happened. Independently, but within just 20 million to 30 million years of one another, all three amniote lineages evolved a tympanic middle ear from parts of the skull and the jaws.2 The tympanic middle ear is the assemblage of tiny bones that connects at one end to an eardrum and at the other end to the oval window, an aperture in the bone of the inner ear. Despite the temporal coincidence in the evolution of these structures in the three amniote lineages and the functional similarities of the adaptations, the groups were by this time so far separated that the middle ears evolved from different structures into two different configurations. The single middle-ear bone, the columella, of archosaurs and lepidosaurs derived from the hyomandibular, a bone that earlier had formed a large strut connecting the braincase to the outer skull.

Research on hearing organs have revealed the remarkable history of this unexpected diversity of ears. Divergence from a common origin Amniote vertebrates comprise three lineages of extant groups that diverged roughly 300 million years ago: the lepidosaurs, which include lizards and snakes; the archosaurs, which include crocodilians and birds; and mammals, which include egg-laying, pouched, and placental mammals. By comparing the skulls of the extinct common ancestors of these three lineages, as well as the ears of the most basal modern amniotes, researchers have concluded that ancestral amniotes had a small (perhaps less than 1 millimeter in length) but dedicated hearing organ: a sensory epithelium called a basilar papilla, with perhaps a few hundred sensory hair cells supported by a thin basilar membrane that is freely suspended in fluid. These rudimentary structures evolved from the hair cells of vestibular organs, which help organisms maintain their balance by responding to physical input, such as head rotation or gravity. Initially, the hearing organ only responded to low-frequency sounds. On their apical surface, all hair cells have tight tufts or bundles of large, hairlike villi known as stereovilli (or, more commonly stereocilia, even though they are not true cilia), which give hair cells their name. Between these stereovilli are proteinaceous links, most of which are closely coupled to sensory transduction channels that respond to a tilting of the stereovilli bundles caused by sound waves.

The amniote hearing organ evolved as a separate group of hair cells that lay between two existing vestibular epithelia. Low-frequency vestibular hair cells became specialized to transduce higher frequencies, requiring much faster response rates. This change is attributable in part to modifications in the ion channels of the cell membrane, such that each cell is “electrically tuned” to a particular frequency, a phenomenon still observed in some modern amniote ears.

MODERN INNER EARS

Arose starting about 200 million years ago In all three lineages, hair cells are arranged along the auditory papilla from low- to high-frequency sensitivity, called a tonotopic organization. In both archosaurs and mammals, one type of hair cell serves to amplify the sound signal received by the other type. In lepidosaurs, the auditory papilla ranges from a few hundred micrometers to 2 millimeters in length and contains two types of hair cells: one with taller bundles and fewer stereovilli that responds to sounds below 1 kHz and another with shorter, thicker bundles that responds to higher-frequency pitches.

The archosaur papilla, which reaches lengths of up to 10 millimeters in some owls, contains many thousands of hair cells of types: tall hair cells, which serve to detect sound, and short hair cells, which amplify the signal. In most mammals, the auditory papilla, called the organ of Corti, evolved to be so long that it began to coil on top of itself. The papilla ranges from 1.5 to 4 coils and 7 millimeters (mouse) to 75 millimeters (blue whale) in length. Mammals have two types of hair cells: covering the oval window, which detect sound, and outer hair cells, which inner hair cells amplify it.

Tectorial membrane

Tall hair cell

Short hair cell

Basilar membrane

Inner

hair cell

Outer

hair cell

In modern representatives, the columella is long and thin, with several, usually cartilaginous extensions known as the extracolumella. One of these, the “inferior process,” connects the inner surface of the eardrum and the columella, which then connects to the footplate that covers the oval window of the inner ear. This two-part system forms a lever that, together with the pressure increase incurred by transmitting from the much larger eardrum to the footplate, greatly magnifies sound entering the inner ear.

In the mammals of the Triassic, the equivalent events were more complex, but the functional result was remarkably similar. Mammal ancestors reduced the number of bones in the lower jaw from seven to one and, in the process, formed a new jaw joint. Initially, the old and new jaw structures existed in parallel, but over time the old joint moved towards the rear of the head. This event, which at any other time would likely have led to the complete loss of the old joint bones, occurred simultaneously with the origin of the mammalian tympanic middle ear. Older paleontological and newer developmental evidence from Shigeru Kuratani’s lab at RIKEN in Japan indicate that the mammalian eardrum evolved at a lower position on the skull relative to that of the other amniotes, a position outside the old jaw joint.3 In time, the bones of this old joint, together with the hyomandibula, became the three bony ossicles (malleus, incus, and stapes) of the new middle ear. Like the middle ear of archosaurs and lepidosaurs, these ossicles form a lever system that, along with the large area difference between eardrum and footplate, greatly magnifies sound input. Thus, remarkably, these complex events led independently to all modern amniotes possessing a middle ear that, at frequencies below 10 kHz, works equally effectively despite the diverse structures and origins. There is also evidence that the three-ossicle mammalian middle ear itself evolved at least twice—in egg-laying mammals such as the platypus, and in therians, which include marsupials and placentals—with similar outcomes.

More…

Aural History

The form and function of the ears of modern land vertebrates cannot be understood without knowing how they evolved.

http://www.the-scientist.com//?articles.view/articleNo/43806/title/Aural-History/

By Geoffrey A. Manley | September 1, 2015

PHOTO CREDITS SEE END OF ARTICLE
http://www.the-scientist.com/Sept2015/feature1.jpg

Unlike eyes, which are generally instantly recognizable, ears differ greatly in their appearance throughout the animal kingdom. Some hearing structures may not be visible at all. For example, camouflaged in the barn owl’s facial ruff—a rim of short, brown feathers surrounding the bird’s white face—are clusters of stiff feathers that act as external ears on either side of its head. These feather structures funnel sound collected by two concave facial disks to the ear canal openings, increasing the bird’s hearing sensitivity by 20 decibels—approximately the difference between normal conversation and shouting. Similar increases in sensitivity result from the large and often mobile external structures, or pinnae, of many mammals, such as cats and bats. Internally, the differences among hearing organs are even more dramatic.

Although fish can hear, only amphibians and true land vertebrates—including the aquatic species that descended from them, such as whales and pinnipeds—have dedicated hearing organs. In land vertebrates belonging to the group Amniota, including lizards, birds, and mammals, sound usually enters through an external canal and impinges on an eardrum that is connected through middle-ear bones to the inner ear. There, hundreds or thousands of sensory hair cells are spread along an elongated membrane that acts as a spectral analyzer, with the result that each local group of hair cells responds best to a certain range of pitches, or sound frequencies. The hair cells then feed this information into afferent nerve fibers that carry the information to the brain. (See “Human Hearing: A Primer.”)

For a period of at least 50 million years after amniotes arose, the three main lineages were most likely quite hard of hearing.

Together, these hair cells and nerve fibers encode a wide range of sounds that enter the ear on that side of the head. Two ears complete the picture, allowing animals’ brains to localize the source of the sounds they hear by comparing the two inputs. Although it seems obvious that the ability to process nearby sounds would be enormously useful, modern amniote ears in fact arose quite late in evolutionary history, and to a large extent independently in different lineages. As a result, external, middle, and inner ears of various amniotes are characteristically different.¹ New paleontological studies and comparative research on hearing organs have revealed the remarkable history of this unexpected diversity of ears.

Divergence from a common origin

Amniote vertebrates comprise three lineages of extant groups that diverged roughly 300 million years ago: the lepidosaurs, which include lizards and snakes; the archosaurs, which include crocodilians and birds; and mammals, which include egg-laying, pouched, and placental mammals. By comparing the skulls of the extinct common ancestors of these three lineages, as well as the ears of the most basal modern amniotes, researchers have concluded that ancestral amniotes had a small (perhaps less than 1 millimeter in length) but dedicated hearing organ: a sensory epithelium called a basilar papilla, with perhaps a few hundred sensory hair cells supported by a thin basilar membrane that is freely suspended in fluid. These rudimentary structures evolved from the hair cells of vestibular organs, which help organisms maintain their balance by responding to physical input, such as head rotation or gravity. Initially, the hearing organ only responded to low-frequency sounds. On their apical surface, all hair cells have tight tufts or bundles of large, hairlike villi known as stereovilli (or, more commonly stereocilia, even though they are not true cilia), which give hair cells their name. Between these stereovilli are proteinaceous links, most of which are closely coupled to sensory transduction channels that respond to a tilting of the stereovilli bundles caused by sound waves.

The amniote hearing organ evolved as a separate group of hair cells that lay between two existing vestibular epithelia. Low-frequency vestibular hair cells became specialized to transduce higher frequencies, requiring much faster response rates. This change is attributable in part to modifications in the ion channels of the cell membrane, such that each cell is “electrically tuned” to a particular frequency, a phenomenon still observed in some modern amniote ears. Moreover, the early evolution of these dedicated auditory organs in land vertebrates led to the loss of the heavy otolithic membrane that overlies the hair-cell bundles of vestibular organs and is responsible for their slow responses. What remains is the watery macromolecular gel known as the tectorial membrane, which assures that local groups of hair cells move synchronously, resulting in greater sensitivity.

Good high-frequency hearing did not exist from the start, however. For a period of at least 50 million years after amniotes arose, the three main lineages were most likely quite hard of hearing. They had not yet evolved any mechanism for absorbing sound energy from air; they lacked the middle ear and eardrum that are vital for the function of modern hearing organs. As such, ancestral amniotes most likely perceived only sounds of relatively low frequency and high amplitude that reached the inner ear via the limbs or, if the skull were rested on the ground, through the tissues of the head. It is unclear what kind of stimuli could have existed that would have led to the retention of such hearing organs for such a long time.

The magnificent middle ear

http://www.the-scientist.com/Sept2015/Manleyonline.jpg

CONVERGING ON THE EAR: Starting around 250 million years ago, the three amniote lineages—lepidosaurs (lizards and snakes), archosaurs (crocodilians and birds), and mammals—separately evolved a tympanic middle ear, followed by evolution of the inner ear, both of which served to increase hearing sensitivity. Despite the independent origin of hearing structures in the three lineages, the outcomes were functionally quite similar, serving as a remarkable example of convergent evolution.
See full infographic: JPG

ILLUSTRATIONS: PHEBE LI FOR THE SCIENTIST. ICONS: ISTOCK.COMDuring the Triassic period, some 250 to 200 million years ago, a truly remarkable thing happened. Independently, but within just 20 million to 30 million years of one another, all three amniote lineages evolved a tympanic middle ear from parts of the skull and the jaws.²

The tympanic middle ear is the assemblage of tiny bones that connects at one end to an eardrum and at the other end to the oval window, an aperture in the bone of the inner ear. Despite the temporal coincidence in the evolution of these structures in the three amniote lineages and the functional similarities of the adaptations, the groups were by this time so far separated that the middle ears evolved from different structures into two different configurations. The single middle-ear bone, the columella, of archosaurs and lepidosaurs derived from the hyomandibular, a bone that earlier had formed a large strut connecting the braincase to the outer skull. In modern representatives, the columella is long and thin, with several, usually cartilaginous extensions known as the extracolumella. One of these, the “inferior process,” connects the inner surface of the eardrum and the columella, which then connects to the footplate that covers the oval window of the inner ear. This two-part system forms a lever that, together with the pressure increase incurred by transmitting from the much larger eardrum to the footplate, greatly magnifies sound entering the inner ear.

In the mammals of the Triassic, the equivalent events were more complex, but the functional result was remarkably similar. Mammal ancestors reduced the number of bones in the lower jaw from seven to one and, in the process, formed a new jaw joint. Initially, the old and new jaw structures existed in parallel, but over time the old joint moved towards the rear of the head. This event, which at any other time would likely have led to the complete loss of the old joint bones, occurred simultaneously with the origin of the mammalian tympanic middle ear. Older paleontological and newer developmental evidence from Shigeru Kuratani’s lab at RIKEN in Japan indicate that the mammalian eardrum evolved at a lower position on the skull relative to that of the other amniotes, a position outside the old jaw joint.³ In time, the bones of this old joint, together with the hyomandibula, became the three bony ossicles (malleus, incus, and stapes) of the new middle ear. Like the middle ear of archosaurs and lepidosaurs, these ossicles form a lever system that, along with the large area difference between eardrum and footplate, greatly magnifies sound input.

Thus, remarkably, these complex events led independently to all modern amniotes possessing a middle ear that, at frequencies below 10 kHz, works equally effectively despite the diverse structures and origins. There is also evidence that the three-ossicle mammalian middle ear itself evolved at least twice—in egg-laying mammals such as the platypus, and in therians, which include marsupials and placentals—with similar outcomes.

Inner-ear evolution

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PITCH PERFECT: The hearing organs of amniotes are organized tonotopically, with hair cells sensitive to high frequencies at the basal end of the papilla, grading into low-frequency hair cells at the apical end.BASED ON MED-EL WWW.MEDEL.COMThe evolution of tympanic middle ears kick-started the evolution of modern inner ears, where sound waves are converted into the electrical signals that are sent to the brain. The inner ear is least developed in the lepidosaurs, most of which retained a relatively small auditory papilla, in some just a few hundred micrometers long. Many lepidosaurs, predominantly diurnal species, also lost their eardrum. Snakes reduced their middle ear, limiting their hearing to frequencies less than 1 kHz, about two octaves above middle C. (For comparison, humans can hear sounds up to about 15 or 16 kHz.) Clearly, hearing was not under strong selective pressure in this group. There are a few exceptions, however. In geckos, for example, which are largely nocturnal, the papillar structure shows unique specializations, accompanied by high sensitivity and strong frequency selectivity. Indeed, the frequency selectivity of gecko auditory nerve fibers exceeds that of many mammals.

One part of the inner ear that did improve in lizards (but not in snakes) is the hair cells, with the papillae developing different areas occupied by two structural types of these sound-responsive cells. One of these hair cell groups responds to sounds below 1 kHz and perhaps corresponds to the ancestral version. The higher-frequency hair cells have a more specialized structure, particularly with regard to the size and height of the stereovilli, with bundle heights and stereovillus numbers varying consistently along the papilla’s length. Taller bundles with fewer stereovilli, which are much less stiff and therefore respond best to low frequencies, are found at one end of the membrane, while shorter, thicker bundles with more stereovilli that respond best to higher frequencies are found at the other end—a frequency distribution known as a tonotopic organization. Still, with the exception of one group of geckos, lizard hearing is limited to below 5 to 8 kHz.

In contrast to the relatively rudimentary lepidosaur inner ear, the auditory papilla of archosaurs (birds, crocodiles, and their relatives) evolved much greater length. Owls, highly proficient nocturnal hunters, boast the longest archosaur papilla, measuring more than 10 millimeters and containing many thousands of hair cells. As in lizards, archosaur hair cells show strong tonotopic organization, with a gradual change in the diameter and height of the stereovillar bundles contributing to the gradually changing frequency sensitivity along the papilla. In addition, the hair cells are divided along and across the basilar membrane, with tall hair cells (THCs) resting on the inner side and the apical end, most distant from the middle ear, grading into short hair cells (SHCs) on the outer side and at the basal end. Interestingly, many SHCs completely lack afferent innervation, which is the only known case of sensory cells lacking a connection to the brain. Instead of transmitting sensory information to the brain, these hair cells likely amplify the signal received by the inner ear. Despite the more complex anatomy, however, bird hearing is also generally limited to between 5 and 8 kHz, with the exception of some owls, which can hear up to 12 kHz.

The mammalian papilla, called the organ of Corti, also evolved to be larger—generally, but not always, longer than those of birds—but the extension in length varies in different lineages.⁴ Mammalian papillae also have a unique cellular arrangement. The papillae of modern egg-laying monotremes, which likely resemble those of the earliest mammals, include two groups of hair cells separated by numerous supporting pillar cells that form the tunnel of Corti. In any given cross section, there are approximately five inner hair cells (IHCs) on the inner side of the pillar cells, closer to the auditory nerve, and eight outer hair cells (OHCs) on the outer side. In therian mammals (marsupials and placentals), the numbers of each cell group have been much reduced, with only two pillar cells forming the tunnel in any given cross-section, and generally just a single IHC and three or four OHCs, though the functional consequences of this reduction remain unclear. About 90 percent of afferent fibers innervate IHCs, while only 10 percent or fewer innervate OHCs, despite the fact that OHCs account for some 80 percent of all hair cells. As with bird SHCs that lack afferent innervation, there are indications that the main function of OHCs is to amplify the physical sound signal at very low sound-pressure levels.

Therian mammals also evolved another key hearing adaptation: the cochlea. Shortly before marsupial and placental lineages diverged, the elongating hearing organ, which had always been curved, reached full circle. The only way to further increase its length was to form more than one full coil, a state that was reached roughly 120 million years ago. The result is hearing organs with 1.5 to 4 coils and lengths from 7 millimeters (mouse) to 75 millimeters (blue whale). Hearing ranges also diverged, partly depending on the size of the animal (larger mammals tend to have lower upper-frequency limits), but with a number of remarkable specializations, as expected in a lineage that radiated greatly during several evolutionary episodes.

As a result of these adaptations, most mammals have an upper frequency-response limit that well exceeds those of lepidosaurs and archosaurs. Human hearing extends to frequencies of about 15 kHz; a guinea pig can hear sounds up to about 45 kHz; and in the extreme cases of many bats and toothed whales, hearing extends into ultrasonic frequencies, sometimes as high as 180 kHz, allowing these animals to echolocate in air and water. This impressive increase in frequency limits is due to an extremely stiff middle ear, as well as a stiff cochlea. During early therian evolution, the bone of the canal surrounding the soft tissues invaded the supporting ridges of the basilar membrane, creating stiff laminae. Such bony ridges were retained in species perceiving ultrasonic frequencies, but tended to be reduced and replaced by softer connective-tissue supports in those with lower-frequency limits, such as humans.

Amplification within the ear

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HAIRS OF THE EAR: Rows of inner-ear hair cells have villous bundles (blue) on their apical surface that convert sound waves to nervous signals sent to the brain.© STEVE GSCHMEISSNER/SCIENCE SOURCEIn addition to the specialized structures of the middle and inner ears of amniotes that served to greatly increase hearing sensitivity, the hair cells themselves can produce active movements that further amplify sound stimuli. The evolutionarily oldest such active mechanism was discovered in the late 1980s by Jim Hudspeth’s group, then at the University of California, San Francisco, School of Medicine, working with frogs,⁵ and Andrew Crawford and Robert Fettiplace, then at the University of Cambridge, working with turtles.⁶ The amplification mechanism, called the active bundle mechanism, probably evolved in the ancestors of vertebrates and helped overcome the viscous forces of the surrounding fluids, which resist movement. When sound stimuli move the hair-cell bundle and thus open transduction channels to admit potassium ions, some calcium ions also enter the cell. These calcium ions bind to and influence the open transduction channels, increasing the speed with which these channels close. Such closing forces are exerted in phase with the incoming sound waves, increasing the distance that the hair cells move in response, and thereby increasing their sensitivity. It is likely that this mechanism operates in all vertebrate hair cells.⁵ In lizards, my group provided evidence that this bundle mechanism really does operate in the living animal.⁷

In 1986, a second mechanism of hair cell–driven sound amplification was discovered in mammalian OHCs by Bill Brownell’s group, then at the University of Florida School of Medicine. Brownell and his colleagues showed that mammalian OHCs, but not IHCs, changed their length very rapidly in phase with the signal if exposed to an alternating electrical field.⁸ Such fields occur when hair cells respond to sound. Subsequent experiments showed that the change in cell length is due to changes in the molecular configuration of a protein, later named prestin, which occurs in high density along the lateral cell membrane of OHCs. In mammals, the force produced by the OHCs is so strong that the entire organ of Corti, which includes all cell types that surround the hair cells and the basilar membrane itself, is driven in an up-and-down motion. This movement can amplify sounds by at least 40dB, allowing very quiet noises to be detected. There is evidence for the independent evolution of specific molecular configurations of prestins that allow for the amplification of very high ultrasonic frequencies in bats and whales.⁹

Bird ears also appear to produce active forces that amplify sound. The SHCs have bundles comprising up to 300 stereovilli (about three times as many as the bundles of mammalian OHCs),¹⁰ and the movement of these bundles probably drives the movement of THCs indirectly via the tectorial membrane. Also, very recent data from the lab of Fettiplace, now at the University of Wisconsin–Madison, suggests that in birds, prestin (albeit in a different molecular form) may work in the plane across the hearing organ (i.e., not up and down as in mammals), perhaps reinforcing the influence of the bundle active mechanism on the THCs via the tectorial membrane.¹¹

Three hundred million years of evolution have resulted in a fascinating variety of ear configurations that, despite their struc­tural diversity, show remarkably similar physiological responses.

In addition to amplifying hair-cell activity, these active mechanisms manifest as spontaneous movements of the hearing organ, oscillating even in the absence of sound stimuli. Such spontaneous movements actually produce sound that is emitted through the middle ear to the outside world and can be measured in the ear canal. These spontaneous otoacoustic emissions (SOAEs) enable remote sensing of what is going on within the inner ear and have permitted increasingly important research on inner-ear mechanisms and new clinical diagnostic methods to monitor the health of the ear’s sensory epithelium. We recently showed that spectral patterns of SOAEs in lizards, birds, and mammals are remarkably similar, despite up to 70-fold differences in the size of the hearing organs, suggesting that there are profound commonalities among the inner ears of amniotes that we still do not really understand.¹²

Remarkable convergence

Three hundred million years of evolution have resulted in a fascinating variety of ear configurations that, despite their structural diversity, show remarkably similar physiological responses. There are hardly any differences in sensitivity between the hearing of endothermal birds and mammals, and the frequency selectivity of responses is essentially the same in most lizards, birds, and mammals. The combined research efforts of paleontologists, anatomists, physiologists, and developmental biologists over several decades have clarified the major evolutionary steps in all lineages that modified the malleable middle and inner ears into their present-day kaleidoscopic variety of form, yet a surprising consensus in their function.

Geoffrey A. Manley is a retired professor from the Institute of Zoology at the Technical University in Munich, Germany. He is currently a guest scientist in the laboratory of his wife, Christine Köppl, at Oldenburg University in Germany.

References

1. G.A. Manley, C. Köppl, “Phylogenetic development of the cochlea and its innervation,” Curr Opin Neurobiol, 8:468-74, 1998.
2. J.A. Clack, “Patterns and processes in the early evolution of the tetrapod ear,” J Neurobiol, 53:251-64, 2002.
3. T. Kitazawa et al., “Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids,” Nat Commun, 6:6853, 2015.
4. G.A. Manley, “Evolutionary paths to mammalian cochleae,” JARO, 13:733-43, 2012.
5. A.J. Hudspeth, “How the ear’s works work: Mechanoelectrical transduction and amplification by hair cells,” C R Biol, 328:155-62, 2005.
6. A.C. Crawford, R. Fettiplace, “The mechanical properties of ciliary bundles of turtle cochlear hair cells,” J Physiol, 364:359-79, 1985.
7. G.A. Manley et al., “In vivo evidence for a cochlear amplifier in the hair-cell bundle of lizards,” PNAS, 98:2826-31, 2001.
8. B. Kachar et al., “Electrokinetic shape changes of cochlear outer hair cells,” Nature, 322:365-68, 1986.
9. Y. Liu et al., “Convergent sequence evolution between echolocating bats and dolphins,” Curr Biol, 20:R53-R54, 2010.
10. C. Köppl et al., “Big and powerful: A model of the contribution of bundle motility to mechanical amplification in hair cells of the bird basilar papilla,” in Concepts and Challenges in the Biophysics of Hearing, ed. N.P. Cooper, D.T. Kemp (Singapore: World Scientific, 2009), 444-50.
11. M. Beurg et al., “A prestin motor in chicken auditory hair cells: Active force generation in a nonmammalian species,” Neuron, 79:69-81, 2013.
12. C. Bergevin et al., “Salient features of otoacoustic emissions are common across tetrapod groups and suggest shared properties of generation mechanisms,” PNAS, 112:3362-67, 2015.

Sea Lion: © iStock/LFStewart; Squirrel: © Erik Mandre/Shutterstock; Frog: ©Frank B. Yuwono/Shutterstock; Owl: ©XNature.Photography/Shutterstock; Lizard: ©Andrew Wijesuriya/Shutterstock; Bat: © iStock/GlobalP; Ostrich: © Jamen Percy/Shutterstock; Dog: ©Annette Shaff/Shutterstock; Lynx: © Dmitri Gomon/Shutterstock

Correction (September 15, 2015): Citation #8 of this story has been updated to accurately reflect the research referenced in the text. The Scientist regrets the error.

Tags

vertebrates, sensory biology, hearing, evolutionary biology, evolution and amniotes

Early Hominin Hearing

http://www.the-scientist.com//?articles.view/articleNo/44119/title/Early-Hominin-Hearing/

Based on the structure of fossilized skulls and ear bones, researchers learn that early hominins heard sounds best between the frequencies that humans and chimpanzees do.

By Karen Zusi | September 29, 2015

africanus skullWIKIMEDIA, JOSÉ BRAGA

http://www.the-scientist.com/images/Nutshell/Sept2015/hominin310.jpg

Early hominin species Australopithecus africanus andParanthropus robustus, which lived around 2 million years ago, possessed hearing capabilities largely similar to modern-day chimpanzees but with a few differences that made their sense more akin to that of humans, according to a recent study. The results were reported last week (September 25) in Science Advances.

“We know that the hearing patterns, or audiograms, in chimpanzees and humans are distinct because their hearing abilities have been measured in the laboratory in living subjects,” study coauthor Rolf Quam of Binghamton University in New York said in a press release. “So we were interested in finding out when this human-like hearing pattern first emerged during our evolutionary history.”

Quam and an international team of researchers studied the anatomy of the ear in three complete fossilized specimens, as well as several partial specimens, from South Africa. The team reconstructed the size and relative proportions of up to six different structures—such as the stapes, a middle ear bone—using 3-D CT scans. The researchers then used a published model to predict how the early hominins may have heard, based on these measurements.

Both species of early hominin evolved an anatomy that allowed them to hear sounds at slightly higher frequencies than chimpanzees, best in the 1.0 kHz to 3.5 kHz range. In comparison, chimpanzees can hear sounds best between 1.0 kHz and 3.0 kHz. Humans can typically hear sounds best between 1.0 kHz and 4.5 kHz; this range encompasses most sounds formed in spoken language.

“[The early hominins] didn’t hear as well as humans, and they are more like chimps,” Quam told The New York Times. But the researchers speculated that the changes in hearing anatomy over time were driven by a lifestyle spent on the open savanna, where short-range communication would have been favored.

“Hearing abilities are closely tied with verbal communication,” Quam wrote at The Conversation. “By figuring out when certain hearing capacities emerged during our evolutionary history, we might be able to shed some light on when spoken language started to evolve.”

Tags

paleontology, human evolution, hominin, hearing, fossils, CT scan and chimpanzee

Hearing Explained

Observe the ins and outs of how our ears perceive sound.

By The Scientist Staff | September 1, 2015

http://www.the-scientist.com//?articles.view/articleNo/43884/title/Hearing-Explained/

Human Hearing: A Primer

How the human ear translates sound waves into nervous impulses

By The Scientist Staff | September 1, 2015

https://youtu.be/46aNGGNPm7s

When sound enters the ear canal, it vibrates the tympanic membrane, or eardrum. These vibrations are passed through the inner ear via three small bones called ossicles: the malleus, the incus, and the stapes. Finally, vibrations of the stapes stimulate the movement of a fluid called perilymph within the bony labyrinth of the inner ear.

See labeled infographic: JPG© CATHERINE DELPHIA

http://www.the-scientist.com/images/August2015/Primer_2.jpg

Perilymph fills the both the vestibular and tympanic ducts of the cochlea. Between these two channels lies the cochlear duct, which is home to the organ of Corti. There, the sound induced movement of perilymph in the cochlea is translated to an electrical signal that is sent to the brain for processing.

An electrical signal is generated by inner hair cells that sit above the basilar membrane, which separates the cochlear duct from the tympanic duct. As the basilar membrane vibrates in response to fluid movement, it pushes the hair cells along another membrane, known as the tectorial membrane, which shifts laterally to bend projections at the tips of the cells, called stereocilia.

The bending of the stereocilia results in the depolarization of the inner hair cell and initiates a nerve impulse through the spiral ganglion neuron at the base of the cell. A series of outer hair cells serves to mechanically amplify the vibrations that trigger the inner hair cells to fire. High-frequency sounds stimulate hair cells at the base of the cochlea, while low-frequency sounds stimulate hair cells at the apex.

See labeled infographic: JPG© CATHERINE DELPHIA

http://www.the-scientist.com/images/August2015/Primer_1.jpg

Tags

spiral ganglion neurons, sensory biology, neuroscience, neurons, mechanotransduction, mechanoreception and hearing

Author of books:
Brain Mechanisms of Vision (1991, with David H. Hubel)
Colloquium on Vision: From Photon to Perception (200, with John Dowling and Lubert Stryer)
Brain and Visual Perception: The Story of a 25-Year Collaboration (2005, with David H. Hubel)

Professor: Physiology, Harvard University (1964-74)
Professor: Neurobiology, Harvard University (1974-84)
Professor: Neurobiology, Rockefeller University (1984-98)
Administrator: President, Rockefeller University (1991-98)

The interplay of light and life

Lubert Stryer (born March 2, 1938, in Tianjin, China) is the Mrs. George A. Winzer Professor of Cell Biology, Emeritus, at the Stanford University School of Medicine.^[1][2] His research over more than four decades has been centered on the interplay of light and life. In 2007 he received the National Medal of Science for elucidating the biochemical basis of signal amplification in vision, pioneering the development of high density micro-arrays for genetic analysis, and authoring the biochemistry textbook.^[3]

Stryer received his B.S. degree from the University of Chicago in 1957 and his M.D. degree from Harvard Medical School. He was a Helen Hay Whitney Research Fellow^[4] in the Department of Physics at Harvard and then at the MRC Laboratory of Molecular Biology^[5] in Cambridge, England, before joining the faculty of the Department of Biochemistry at Stanford in 1963. In 1969 he moved to Yale to become Professor of Molecular Biophysics and Biochemistry, and in 1976, he returned to Stanford to head a new Department of Structural Biology.^[6]

Stryer and coworkers pioneered the use of fluorescence spectroscopy, particularly Förster resonance energy transfer (FRET), to monitor the structure and dynamics of biological macromolecules.^[7][8] In 1967, Stryer and Haugland showed that the efficiency of energy transfer depends on the inverse sixth power of the distance between the donor and acceptor,^[9][10] as predicted by Förster’s theory. They proposed that energy transfer can serve as a spectroscopic ruler to reveal proximity relationships in biological macromolecules.

A second contribution was Stryer’s discovery of the primary stage of amplification in visual excitation.^[11][12] Stryer, together with Fung and Hurley, showed that a single photoexcited rhodopsin molecule activates many molecules of transducin, which in turn activate many molecules of a cyclic GMP phosphodiesterase. Stryer’s laboratory has also contributed to our understanding of the role of calcium in visual recovery and adaptation.^[13][14][15]

Stryer participated in developing light-directed, spatially addressable parallel chemical synthesis for the synthesis of peptides and polynucleotides.^[16][17][18] Light-directed combinatorial synthesis has been used by Stephen Fodor and coworkers at Affymetrix to make DNA arrays containing millions of different sequences for genetic analyses.

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