Transferring an inborn auditory perceptual predisposition with interspecies brain transplants

Inborn species' perceptual preferences are thought to serve as important guides for neonatal learning in most species of higher vertebrates. Although much work has been carried out on experiential contributions to the expression of such preferences, their neural and developmental correlates remain largely unexplored. Here we use embryonic neural transplants between two bird species, the Japanese quail and the domestic chicken, to demonstrate that an inborn auditory perceptual predisposition is transferable between species. The transfer of the perceptual preference was dissociated from changes to the vocalizations of the resulting animals (called chimeras), suggesting that experiential differences in auditory self-stimulation cannot explain the perceptual change. A preliminary localization of the effective brain region for the behavioral transfer by using a naturally occurring species-cell marker revealed that it is not contained within the major avian auditory pathways. To our knowledge, this is the first demonstration that abstract aspects of auditory perception can be transferred between species with transplants of the central nervous system.

Rapidly induced auditory plasticity: The ventriloquism aftereffect

Cortical representational plasticity has been well documented after peripheral and central injuries or improvements in perceptual and motor abilities. This has led to inferences that the changes in cortical representations parallel and account for the improvement in performance during the period of skill acquisition. There have also been several examples of rapidly induced changes in cortical neuronal response properties, for example, by intracortical microstimulation or by classical conditioning paradigms. This report describes similar rapidly induced changes in a cortically mediated perception in human subjects, the ventriloquism aftereffect, which presumably reflects a corresponding change in the cortical representation of acoustic space. The ventriloquism aftereffect describes an enduring shift in the perception of the spatial location of acoustic stimuli after a period of exposure of spatially disparate and simultaneously presented acoustic and visual stimuli. Exposure of a mismatch of 8° for 20–30 min is sufficient to shift the perception of acoustic space by approximately the same amount across subjects and acoustic frequencies. Given that the cerebral cortex is necessary for the perception of acoustic space, it is likely that the ventriloquism aftereffect reflects a change in the cortical representation of acoustic space. Comparisons between the responses of single cortical neurons in the behaving macaque monkey and the stimulus parameters that give rise to the ventriloquism aftereffect suggest that the changes in the cortical representation of acoustic space may begin as early as the primary auditory cortex.

Auditory neuroscience: Development, transduction, and integration

Hearing underlies our ability to locate sound sources in the environment, our appreciation of music, and our ability to communicate. Participants in the National Academy of Sciences colloquium on Auditory Neuroscience: Development, Transduction, and Integration presented research results bearing on four key issues in auditory research. How does the complex inner ear develop? How does the cochlea transduce sounds into electrical signals? How does the brain's ability to compute the location of a sound source develop? How does the forebrain analyze complex sounds, particularly species-specific communications? This article provides an introduction to the papers stemming from the meeting.

Cellular studies of auditory hair cell regeneration in birds

A decade ago it was discovered that mature birds are able to regenerate hair cells, the receptors for auditory perception. This surprising finding generated hope in the field of auditory neuroscience that new hair cells someday may be coaxed to form in another class of warm-blooded vertebrates, mammals. We have made considerable progress toward understanding some cellular and molecular events that lead to hair cell regeneration in birds. This review discusses our current understanding of avian hair cell regeneration, with some comparisons to other vertebrate classes and other regenerative systems.

Mechanical bases of frequency tuning and neural excitation at the base of the cochlea: Comparison of basilar-membrane vibrations and auditory-nerve-fiber responses in chinchilla

We review the mechanical origin of auditory-nerve excitation, focusing on comparisons of the magnitudes and phases of basilar-membrane (BM) vibrations and auditory-nerve fiber responses to tones at a basal site of the chinchilla cochlea with characteristic frequency ≈ 9 kHz located 3.5 mm from the oval window. At this location, characteristic frequency thresholds of fibers with high spontaneous activity correspond to magnitudes of BM displacement or velocity in the order of 1 nm or 50 μm/s. Over a wide range of stimulus frequencies, neural thresholds are not determined solely by BM displacement but rather by a function of both displacement and velocity. Near-threshold, auditory-nerve responses to low-frequency tones are synchronous with peak BM velocity toward scala tympani but at 80–90 dB sound pressure level (in decibels relative to 20 microPascals) and at 100–110 dB sound pressure level responses undergo two large phase shifts approaching 180°. These drastic phase changes have no counterparts in BM vibrations. Thus, although at threshold levels the encoding of BM vibrations into spike trains appears to involve only relatively minor signal transformations, the polarity of auditory-nerve responses does not conform with traditional views of how BM vibrations are transmitted to the inner hair cells. The response polarity at threshold levels, as well as the intensity-dependent phase changes, apparently reflect micromechanical interactions between the organ of Corti, the tectorial membrane and the subtectorial fluid, and/or electrical and synaptic processes at the inner hair cells.

Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus

The anatomical and biophysical specializations of octopus cells allow them to detect the coincident firing of groups of auditory nerve fibers and to convey the precise timing of that coincidence to their targets. Octopus cells occupy a sharply defined region of the most caudal and dorsal part of the mammalian ventral cochlear nucleus. The dendrites of octopus cells cross the bundle of auditory nerve fibers just proximal to where the fibers leave the ventral and enter the dorsal cochlear nucleus, each octopus cell spanning about one-third of the tonotopic array. Octopus cells are excited by auditory nerve fibers through the activation of rapid, calcium-permeable, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors. Synaptic responses are shaped by the unusual biophysical characteristics of octopus cells. Octopus cells have very low input resistances (about 7 MΩ), and short time constants (about 200 μsec) as a consequence of the activation at rest of a hyperpolarization-activated mixed-cation conductance and a low-threshold, depolarization-activated potassium conductance. The low input resistance causes rapid synaptic currents to generate rapid and small synaptic potentials. Summation of small synaptic potentials from many fibers is required to bring an octopus cell to threshold. Not only does the low input resistance make individual excitatory postsynaptic potentials brief so that they must be generated within 1 msec to sum but also the voltage-sensitive conductances of octopus cells prevent firing if the activation of auditory nerve inputs is not sufficiently synchronous and depolarization is not sufficiently rapid. In vivo in cats, octopus cells can fire rapidly and respond with exceptionally well-timed action potentials to periodic, broadband sounds such as clicks. Thus both the anatomical specializations and the biophysical specializations make octopus cells detectors of the coincident firing of their auditory nerve fiber inputs.

Subdivisions of auditory cortex and processing streams in primates

The auditory system of monkeys includes a large number of interconnected subcortical nuclei and cortical areas. At subcortical levels, the structural components of the auditory system of monkeys resemble those of nonprimates, but the organization at cortical levels is different. In monkeys, the ventral nucleus of the medial geniculate complex projects in parallel to a core of three primary-like auditory areas, AI, R, and RT, constituting the first stage of cortical processing. These areas interconnect and project to the homotopic and other locations in the opposite cerebral hemisphere and to a surrounding array of eight proposed belt areas as a second stage of cortical processing. The belt areas in turn project in overlapping patterns to a lateral parabelt region with at least rostral and caudal subdivisions as a third stage of cortical processing. The divisions of the parabelt distribute to adjoining auditory and multimodal regions of the temporal lobe and to four functionally distinct regions of the frontal lobe. Histochemically, chimpanzees and humans have an auditory core that closely resembles that of monkeys. The challenge for future researchers is to understand how this complex system in monkeys analyzes and utilizes auditory information.

Traces of learning in the auditory localization pathway

One of the fascinating properties of the central nervous system is its ability to learn: the ability to alter its functional properties adaptively as a consequence of the interactions of an animal with the environment. The auditory localization pathway provides an opportunity to observe such adaptive changes and to study the cellular mechanisms that underlie them. The midbrain localization pathway creates a multimodal map of space that represents the nervous system's associations of auditory cues with locations in visual space. Various manipulations of auditory or visual experience, especially during early life, that change the relationship between auditory cues and locations in space lead to adaptive changes in auditory localization behavior and to corresponding changes in the functional and anatomical properties of this pathway. Traces of this early learning persist into adulthood, enabling adults to reacquire patterns of connectivity that were learned initially during the juvenile period.

Plasticity in the neural coding of auditory space in the mammalian brain

Sound localization relies on the neural processing of monaural and binaural spatial cues that arise from the way sounds interact with the head and external ears. Neurophysiological studies of animals raised with abnormal sensory inputs show that the map of auditory space in the superior colliculus is shaped during development by both auditory and visual experience. An example of this plasticity is provided by monaural occlusion during infancy, which leads to compensatory changes in auditory spatial tuning that tend to preserve the alignment between the neural representations of visual and auditory space. Adaptive changes also take place in sound localization behavior, as demonstrated by the fact that ferrets raised and tested with one ear plugged learn to localize as accurately as control animals. In both cases, these adjustments may involve greater use of monaural spectral cues provided by the other ear. Although plasticity in the auditory space map seems to be restricted to development, adult ferrets show some recovery of sound localization behavior after long-term monaural occlusion. The capacity for behavioral adaptation is, however, task dependent, because auditory spatial acuity and binaural unmasking (a measure of the spatial contribution to the “cocktail party effect”) are permanently impaired by chronically plugging one ear, both in infancy but especially in adulthood. Experience-induced plasticity allows the neural circuitry underlying sound localization to be customized to individual characteristics, such as the size and shape of the head and ears, and to compensate for natural conductive hearing losses, including those associated with middle ear disease in infancy.

Spatial processing in the auditory cortex of the macaque monkey

The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel “what” and “where” processing by the primate visual cortex. If “where” information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models

The hepatocyte growth factor (HGF/SF) receptor, Met, regulates mitogenesis, motility, and morphogenesis in a cell type-dependent fashion. Activation of Met via autocrine, paracrine, or mutational mechanisms can lead to tumorigenesis and metastasis and numerous studies have linked inappropriate expression of this ligand-receptor pair to most types of human solid tumors. To prepare mAbs to human HGF/SF, mice were immunized with native and denatured preparations of the ligand. Recloned mAbs were tested in vitro for blocking activity against scattering and branching morphogenesis. Our results show that no single mAb was capable of neutralizing the in vitro activity of HGF/SF, and that the ligand possesses a minimum of three epitopes that must be blocked to prevent Met tyrosine kinase activation. In vivo, the neutralizing mAb combination inhibited s.c. growth in athymic nu/nu mice of tumors dependent on an autocrine Met-HGF/SF loop. Importantly, growth of human glioblastoma multiforme xenografts expressing Met and HGF/SF were markedly reduced in the presence of HGF/SF-neutralizing mAbs. These results suggest interrupting autocrine and/or paracrine Met-HGF/SF signaling in tumors dependent on this pathway is a possible intervention strategy.

Modular organization of intrinsic connections associated with spectral tuning in cat auditory cortex

Many response properties in primary auditory cortex (AI) are segregated spatially and organized topographically as those in primary visual cortex. Intensive study has not revealed an intrinsic, anatomical organizing principle related to an AI functional topography. We used retrograde anatomic tracing and topographic physiologic mapping of acoustic response properties to reveal long-range (≥1.5 mm) convergent intrinsic horizontal connections between AI subregions with similar bandwidth and characteristic frequency selectivity. This suggests a modular organization for processing spectral bandwidth in AI.

T-cell alpha beta + and gamma delta + deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium.

Vertebrate immune systems contain T cells bearing either alpha beta or gamma delta T-cell antigen receptors (TCRs). alpha beta T cells perform all well-characterized T-cell effector functions, while the biological functions of gamma delta + cells remain unclear. Of particular interest is the role of gamma delta + cells during epithelial infections, since gamma delta + cells are commonly abundant within epithelia. Eimeria spp. are intracellular protozoa that infect epithelia of most vertebrates, causing coccidiosis. This study shows that in response to Eimeria vermiformis, mice lacking alpha beta T cells display defects in protective immunity, while mice lacking gamma delta + cells display exaggerated intestinal damage, apparently due to a failure to regulate the consequences of the alpha beta T cell response. An immuno-downregulatory role during infection, and during autoimmune disease, may be a general one for gamma delta + cells.