Ear Of Guinea Pig Research Articles

「内耳形態と細胞機能の研究手法」３．ＭＲＩによる内耳形態の観察

We introduce a method to diagnose sensorineural hearing loss and vestibular disorder using magnetic resonance imaging (MRI). The main pathological finding in patients with Meniere's disease is distention of the entire endolymphatic system, i.e., endolymphatic hydrops, and its diagnosis depends primarily upon a history of fluctuating hearing loss and tinnitus, as well as episodic vertigo associated with vegetative symptoms. Therefore, the development of a practical tool to obtain objective evidence of the existence of endolymphatic hydrops is important. We applied a high-resolution magnetic resonance imaging device running at 2.11 T, 4.7 T, and 7.05 T for the non-invasive depiction of the fine structure of the inner ear in humans and guinea pigs. We have succeeded in depicting both the basilar and Reissner's membranes of the basal turn of the cochlea. In this paper, we present our results using high-resolution MRI and discuss the current status in this field. We suggest the possibility of using MRI for the morphological and functional diagnosis of inner ear pathology in the near future.

Does topical application of 5-fluorouracil ointment influence inner ear function?

To investigate the effect of 5-fluorouracil (5-FU) ointment on the inner ear of guinea pigs. In group A (n = 7), 5-FU ointment was applied into the left external auditory canal. In group B (n = 10), 5-FU ointment was applied to the left middle ear through myringotomy. In both groups, the right ear served as a control. One week later the endocochlear DC potential (EP) was measured and morphology of the cochleae was examined using scanning electron microscopy (SEM) and light microscopy. In group A, there was no significant difference between the EP values of the experimental side and the control side. In group B, there was a statistically significant difference between them (P < 0.05). Morphologic findings showed no damage. 5-FU ointment application to the external ear seems to be safe but its application to the middle ear may pose some risk of ototoxicity.

The Anatomical Record and the ear: From transplanting embryonic bits and pieces to uncovering genes

“Structure and Function in the Auditory System: From Cochlea to Cortex,” is a continuation of a long tradition of insightful, often innovative, research on the ear and auditory function that has appeared within the pages of our journal. Indeed, The Anatomical Record has a robust history of creative studies by leading scientists on topics as diverse as the embryogenesis of the vertebrate ear, the anatomy underling ear function, and evolutionary changes that have affected the ear and contiguous portions of the temporal bone. For example, in the first half of the 20 century renowned anatomists and embryologists G.L. Streeter, T.H. Bast, and B.J Anson published many of their seminal observations on aspects of early ear development in The Anatomical Record. In the early decades of the century, George Streeter’s innovative experiments on transplanting the ear vesicles of tadpoles (1909, 3:199; 1921, 21:114) was amongst the first to chart systematically the developmental migration and positioning of ear components. The studies by both Bast (e.g., 1928, 40:61; 1931, 48: 141; 1947, 99:55) and Anson (e.g., 1929, 43:251; 1934, 58:127) focused upon human embryos, and provided the first descriptions of the ossification sequence of the otic capsule, timing of the development of the ossicles, and the appearance of the blood supply. The Anatomical Record has also been a particularly good home for those using animals as model systems to understand ear function. Notable in these areas were the work of J.C. Sandison (1924, 28:281; 1928, 40:41) at the University of Pennsylvania who pioneered methods of studying living cells and tissues in rabbit ears and extensions of this work by E.R. Clark and colleagues (1930, 47:187); experimental studies by L. Loeb and colleagues (1930, 46:55) on guinea pig ears; comparative work by H.D. Reed (1915, 9:581) on mudpuppies and their kin; and by L.T. Evans (1936, 64:187) on the cochlea in geckos. More recently in the 1990s, during my own tenure with the journal, the Swiss team of Ponce de Leon and Zollikofer (1998, 254:474) have used computerized reconstructions and micro-CT analysis to analyze the ossicles, cochlea and semicircular canals in their elegant study of the fossil Neanderthal skull from Le Moustier and bring us closer to understanding how this region may have functioned in our long-lost relatives. This special issue carries on the century of auditory science research reported in The Anatomical Record, and takes us from descriptions of bits and pieces of underlying anatomy to the genes responsible for setting the scaffold of the ear and its connections to the brain. It proudly carries on — and advances — a noble heritage of reporting the finest science in auditory research.

Spontaneous Basilar-Membrane Oscillation (SBMO) and Coherent Reflection

In a previous report (in JARO) we have described a relatively high-frequency (15 kHz) spontaneous oscillation of the basilar membrane (SBMO) in a guinea pig ear; this oscillation was accompanied by a spontaneous otoacoustic emission (SOAE) at the same frequency. During the spontaneous oscillation and after it had subsided, the mechanical frequency response of the basilar membrane was measured by way of a wide-band random-noise stimulus, and it showed a number of spectral peaks, one of which having the frequency of the original oscillation. This pattern of peaks cannot be explained by assuming a single place of reflection in the cochlea. In this paper the process of 'coherent reflection' is artificially evoked in a three-dimensional model of the cochlea by imposing random place-fixed irregularities to the basilar-membrane impedance. It is shown that in the model a series of peaks arises in the frequency spectrum of the basilar-membrane response which phenomenon resembles the one found in the experimental animal. It is also shown that these peaks are actually due to superposition of the primary wave and a wave resulting from 'coherent reflection' which is reflected at the stapes. When the intensity of the acoustic stimulus signal is increased, the relative sizes of these peaks in the simulation diminish in about the same way as in the experiment. It is concluded that coherent reflection most likely is the cause of the 'extra peaks', and that this concept can also explain the observed level dependence of these peaks. The findings of this study lead to a minor refinement regarding the actual requirements for coherent reflection to arise.

A New Method for Drug Application to the Inner Ear

Inner ear sensory cells are very susceptible to injuries and recovery after damage is very difficult. Recently several drugs including neurotrophic factors have been reported to protect against inner ear injury. The purpose of this experimental study is to find new methods for applying drugs to the inner ear that effectively protect against inner ear damage. Biodegradable hydrogel was used as a carrier for application of brain-derived neurotrophic factor (BDNF) into the inner ear of guinea pigs through the round window membrane. After application of BDNF the number of surviving spiral ganglion neurons increased following injury of inner ear hair cells and spiral ganglion neurons by ototoxic treatment. This result indicates that BDNF provides effective protection against inner ear damage and that biodegradable hydrogel is useful for application of drugs to the inner ear.

Effects of Lithium on Endolymph Homeostasis and Experimentally Induced Endolymphatic Hydrops

There is evidence to suggest that water homeostasis in the inner ear is regulated via the vasopressin (VP)-aquaporin 2 (AQP2) system in the same fashion as in the kidney. The VP-AQP2 system in the kidney is well known to be inhibited by lithium, resulting in polyuria due to a decrease in reabsorption of water in the collecting duct of the kidney. Therefore, lithium is also likely to inhibit the VP-AQP2 system in the inner ear, and consequently exert some influence on inner ear fluid homeostasis. In this study, we investigated the effects of lithium on AQP2 expression in the rat inner ear, and on the cochlear fluid volume in hydropic ears of guinea pigs. A quantitative PCR study revealed that lithium reduced AQP2 mRNA expression in the cochlea and endolymphatic sac. Lithium application also decreased the immunoreactivity of AQP2 in the cochlea and endolymphatic sac. In a morphological study, lithium intake significantly reduced endolymphatic hydrops dose-dependently. These results indicate that lithium acts on the VP-AQP2 system in the inner ear, consequently producing a dehydratic effect on the endolymphatic compartment.

Effect of dantrolene on lipid peroxidation, glutathione and glutathione-dependent enzyme activities in experimental otitis media with effusion in guinea pigs

The aims of our study were to assess whether the increased oxidative stress in experimental otitis media with effusion (OME) induced by histamine was reflected erythrocytes and middle ear effusion fluid by lipid peroxidation; to survey the alterations in antioxidant enzyme activities in experimental OME; and to determine the effect of dantrolene on this oxidative stress. Erythrocyte and middle ear effusion malondialdehyde (MDA) level, erythrocyte glutathione (GSH) and glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST) activities were measured in three groups of seven guinea pigs, 3 hours after injection of 0.1 mL of histamine (or saline) into the middle ear in guinea pigs with OME (experimental group), in a dantrolene sodium group and in a control group. Erythrocyte and effusion MDA levels in the dantrolene group were significantly lower than those of the experimental group. Erythrocyte GSH-Px, GST, GRD activities, and GSH levels were significantly higher in the dantrolene group than in the experimental group. Dantrolene sodium decreased the erythrocyte and effusion MDA levels, on the other hand, it increased the GSH and GSH-dependent enzymes. These findings suggest that reactive oxygen species (ROS) play a role in histamine-induced OME. Pre-treatment with dantrolene sodium increases antioxidant enzymes activities and decreases formation of MDA, the indicator of lipid peroxidation, in histamine-induced OME.

Endothelial nitric oxide synthase upregulation in the cochlea of the guinea pig after intratympanic gentamicin injection

Single-shot transtympanic gentamicin therapy has become a popular treatment modality for Meniere's disease despite the known possible ototoxic properties of this drug. It was shown recently that NO production and iNOS were upregulated after gentamicin application, which was interpreted as a possible effect of ototoxicity. In this study we analyzed the expression of eNOS after gentamicin application to determine a possible correlation of this enzyme with gentamicin-induced ototoxicity. We compared eNOS expression in gentamicin-treated and non-treated guinea pigs in the second turn of the cochlea, an area corresponding to speech perception in humans. Gentamicin (4 mg) was injected intratympanically into the middle ear of guinea pigs ( n =3) and the reduction of the hearing threshold level was determined by recording acoustic-evoked potentials (AEP) before and 5 days after gentamicin application. Morphological alterations in the organ of Corti were analyzed by light and electron microscopy. Gold-labeled anti-eNOS antibodies were counted in eight different cell areas for quantification of eNOS expression. Seven animals were analyzed as controls. After gentamicin application, a deterioration of hearing level was observed varying from 10 to 30 dB. A high degree of vacuolization was identified in the third row of outer hair cells. At the subcellular level, the subsurface cisterns in outer hair cells were dissociated from the basolateral cell membrane, and the mitochondrial membranes were frequently damaged. Statistically significant upregulation of eNOS was observed in all cell types analyzed. Depending on the various cell types the amount of gold-labeled eNOS antibodies was 2.5 to 5.7 times higher after gentamicin application. We observed significant eNOS upregulation after gentamicin application in the cochlea, in conjunction with cellular damages and decreased hearing.

664. Regeneration of Sensory Cells in the Inner Ear of Deafened Mature Guinea Pigs

Top of pageAbstract The mammalian organ of Corti, the sensory epithelium of the inner ear, is a mosaic composed of sensory cells (hair cells) and non- sensory supporting cells. All cells are highly differentiated in structure and function. Because no undifferentiated cells are held in reserve to replace damaged cells, hearing impairment due to loss of hair cells is permanent. Differentiation of complex tissues like the organ of Corti typically is governed by specific cascades of gene expression. In mice, a critical gene in the differentiation of hair cells is the basic helix-loop-helix transcription factor Atoh1(=Math1), a homolog of the Drosophila gene atonal. Previous studies have shown that inoculating inner ears of normal adult guinea pigs with an adenovirus vector expressing Math1 (Ad.Math1) can generate new cochlear hair cells in regions normally occupied only by supporting cells. In this study, we deafened adult guinea pigs by administration with ototoxic drugs (kanamycin and ethacrynic acid) prior to inoculating their inner ears with Ad.Math1 and evaluated differences in hair cell number and hearing thresholds before and after treatment.

Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear

The cochlear sensory epithelium and spiral ganglion neurons (SGNs) in the adult mammalian inner ear do not regenerate following severe injury. To replace the degenerated SGNs, neural stem cell (NSC) is an attractive alternative for substitution cell therapy. In this study, adult mouse NSCs were transplanted into normal and deafened inner ears of guinea pigs. To more efficiently drive the implanted cells into a neuronal fate, NSCs were also transduced with neurogenin 2 ( ngn2) before transplantation. In deafened inner ears and in animals transplanted with ngn2-transduced NSCs, surviving cells expressed the neuronal marker neural class III β-tubulin. Transplanted cells were found close to the sensory epithelium and adjacent to the SGNs and their peripheral processes. The results illustrate that adult NSCs can survive and differentiate in the injured inner ear. It also demonstrates the feasibility of gene transfer to generate specific progeny for cell replacement therapy in the inner ear.

Hearing loss with semicircular canal transection and Pseudomonas aeruginosa otitis media

Objective To determine if Pseudomonas aeruginosa (PA) otitis media (OM) increases the risk of sensorineural hearing loss (SNHL) with semicircular canal transection in the guinea pig model. Methods PA was injected transtympanically into both middle ears of pigmented guinea pigs. Saline-injected animals served as controls. Two to 4 days after injection, one horizontal semicircular canal was transected and sealed. Hearing was tested using electrocochleography before and after transection. Results PA-OM was induced in all PA-injected ears. Five days after semicircular canal transection, click-evoked thresholds were significantly elevated in ears with PA-OM ( P = 0.00009) but not in saline-injected ears ( P = 0.398). Conclusion Violation of the inner ear in the presence of PA-OM is associated with increased risk of SNHL in the guinea pig. Significance Factors unique to PA infection may be responsible for SNHL with labyrinthine injury in humans with chronic otitis media.

Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine.

Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Meniere's disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca2+ channels, may directly target vestibular hair cells where Ca2+ currents are important for the mechano-electrical transduction and transmitter release. Our aim was to clarify whether cinnarizine affected voltage-dependent Ca2+ currents in vestibular type II hair cells. Such cells were isolated from inner ears of guinea pigs by enzymatic and mechanical dissection from the gelatinous otolithic membrane and studied with the patch-clamp technique in conventional whole-cell mode. Ca2+ currents were elicited by depolarizing pulses in a solution containing 1.8 mM Ca2+ and 40 mM Ba2+. These currents resembled L-type currents (I(Ca,L)) with respect to their voltage-dependence and their inhibition by nifedipine and Cd2+ but did not show time-dependent inactivation. The currents were inhibited by cinnarizine in a concentration-dependent and reversible manner. The IC50 was 1.5 microM. A block exceeding 80% was achieved with 10 microM. The onset of current block was faster with higher concentrations but the reversibility after wash-out was less, suggesting accumulation in the membrane. We conclude that these direct actions of cinnarizine on hair cells should be considered as molecular mechanisms contributing to therapeutic effects of cinnarizine in vertigo.

Adenovirus-Mediated Expression of Brain-Derived Neurotrophic Factor Protects Spiral Ganglion Neurons from Ototoxic Damage

Hair cell loss, the most common cause of deafness, is often associated with auditory nerve degeneration. Our goal was to determine the influence of combined ciliary-derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) gene therapy on the survival of spiral ganglion neurons (SGNs) after elimination of inner hair cells in the mature guinea pig ear. Seven days after bilateral deafening, a 5-µl suspension of CNTF and/or BDNF adenovirus vectors was injected into the left scala tympani through the round window. Animals were sacrificed 28 days after deafening, and their inner ears were prepared for SGN counts. The SGN counts revealed that BDNF alone and the combined CNTF and BDNF treatment significantly enhanced SGN survival. CNTF did not significantly enhance the protective effect of BDNF. These data present possible strategies for enhancing SGN survival in cochlear implant procedures.

Inner Ear Changes With Intracochlear Gentamicin Administration in Guinea Pigs

Transtympanic administration of gentamicin is reported to be a useful treatment for vertigo in such conditions as Meniere's disease, and determining appropriate clinical dosage of gentamicin is difficult. The authors examined the relation between gentamicin dosages and inner ear function in guinea pigs. This study is a basic science project designed to examine cochlear and vestibular function in animal models. Various concentrations of gentamicin solution were infused into the right inner ear of guinea pigs by osmotic pumps. Caloric nystagmus as a marker of vestibular function and the change in auditory brainstem response (ABR) threshold as a marker of cochlear function were observed. After 14 days of treatment, high gentamicin concentrations of 40 mg/mL caused canal paralysis and a rapid shift in ABR threshold. Animals exposed to low gentamicin concentrations of 4 mg/mL showed no obvious change in either vestibular or cochlear function. Animals exposed to moderate gentamicin concentrations of 12 mg/mL showed a moderate shift in ABR threshold and caloric malfunction. Histopathological examination revealed that after 14 days of treatment with 40 mg/mL gentamicin, severe cytoplasmic damage occurred in both vestibular and cochlear end organs. In animals treated with 12 mg/mL gentamicin, hair cells remained in the cochlear third turn and ampulla of the lateral semicircular canal. The authors established an animal model that showed the moderate damage of inner ear with moderate-dose gentamicin. The study results indicated that the appropriate administration of gentamicin could establish a stable effect on the inner ear. It may be important to select the protocol that delivers a stable dosage of gentamicin to treat patients with Meniere's disease safely and effectively.

Hearing loss with semicircular canal fistula in exotoxin A–deficient Pseudomonas otitis media

Objective The study goal was to compare the severity of hearing loss with semicircular canal injury in the presence of otitis media (OM) due to an exotoxin A–producing strain of Pseudomonas aeruginosa (PA+) and an exotoxin A–deficient daughter strain (PA−). Methods PA+ or PA− was injected bilaterally into guinea pig ears. Three days later, unilateral lateral semicircular canal transection was performed. Hearing was tested before and after transection. Results PA OM was induced in all injected ears. Significant elevation of click and 12-kHz thresholds ( P < 0.0001) were encountered in PA+-infected ears. No significant threshold elevations were encountered in PA−-infected ears. Conclusion Hearing loss resulting from canal injury in the presence of Pseudomonas OM may be mediated by exotoxin A. Significance Treatment to neutralize the effects of exotoxin A may minimize the risk of hearing loss with canal fistula in chronic OM.

Effects of exposure of the ear to GSM microwaves: in vivo and in vitro experimental studies

The effects of mobile phone (GSM) microwaves on the ears of guinea pigs were investigated in two in vivo experiments and one in vitro experiment. In the first experiment, three groups of eight guinea pigs had their left ear exposed for 1 h/day, 5 days/week, for 2 months, to GSM microwaves (900 MHz, GSM modulated) at specific absorption rates (SARs) of 1, 2 and 4 W/kg respectively, and a fourth group was sham-exposed. Distortion-product otoacoustic emissions (DPOAEs) were measured for each ear before exposure, at the end of the 2-month exposure period, and 2 months later. In the second experiment, the same protocol was applied to eight sham-exposed and 16 exposed guinea pigs at 4 W/kg, but the auditory brainstem response (ABR) thresholds were monitored. Repeated-measures ANOVA showed no difference in DPOAE amplitudes or in ABR thresholds between the exposed and non-exposed ears and between the sham-exposed and exposed groups. In the course of the second experiment, acute effects were also investigated by measuring once, in all animals, ABR thresholds just before and just after the 1-h exposure: no statistically significant difference was observed. In vitro, the two organs of Corti (OCs) of newborn rats (n = 15) were isolated and placed in culture. For each animal, one OC was exposed for 24–48 h to 1 W/kg GSM microwaves, and the other was sham-exposed. After 2–3 days of culture, all OCs were observed under light microscopy. They all appeared normal to naive observers at this stage of development. These results provided no evidence that microwave radiation, at the levels produced by mobile phones, caused damage to the inner ear or the auditory pathways in our experimental animals.

Hearing loss with stapedotomy in otitis media

Objective Stapes fixation is often found in patients with either active or inactive otitis media (OM). Stapedotomy is generally not performed in ears with OM because of the potential risk of sensorineural hearing loss (SNHL). Recent studies have demonstrated that the inner ear may be fenestrated in the presence of OM without significantly increased risk of SNHL. The goal of this study was to determine if stapedotomy in the presence of OM significantly increases the incidence of postoperative SNHL. Methods Streptococcus pneumoniae or Pseudomonas aeruginosa was injected bilaterally into the middle ears of guinea pigs (n = 18 and 16, respectively). A control group (n = 14) was injected with saline solution. Two days postinjection, a unilateral stapedotomy was performed. Auditory thresholds were evaluated by electrocochleography before and after stapedotomy. Results Bacterial OM was induced in all ears injected with pneumococci and pseudomonas. Auditory thresholds increased in all ears treated with stapedotomy. Stapedotomy performed in the presence of pseudomonas OM resulted in significantly greater SNHL than in control or pneumococcal ears ( P = 0.0055). Hearing thresholds were not significantly different between pneumococcal OM and control ears treated with stapedotomy. Conclusion Stapedotomy in the presence of pseudomonas OM, but not pneumococcal OM, significantly increases the risk of SNHL in the guinea pig model. Significance Stapedotomy should be avoided in patients with active OM, particularly in the presence of pseudomonas.

Hyperbaric compression in the guinea pig with perilymph fistula

Objective The study goal was to evaluate the effects of hyperbaric therapy on the auditory and vestibular function of guinea pigs compromised by perilymph fistula (PLF). Methods Twenty-four pigmented guinea pigs underwent induction of bilateral eustachian tube dysfunction before the creation of a unilateral PLF. Half of the animals were randomly assigned to receive immediate hyperbaric compression treatment of 4 “dives” each. Hearing was tested electrocochleographically, and signs of vestibulopathy were recorded before and after compression. Results After accounting for the effects of PLF, compression was not associated with significant hearing loss ( P = 0.5411). Vestibulopathy was seen only in ears with PLF, and its incidence was similar for compression and noncompression groups. Conclusion Hyperbaric compression does not compromise auditory or vestibular function in guinea pig ears with experimental PLF. Significance Our observations support the relative safety of recompression in patients with PLF.

Tratamento cirúrgico da otite média com efusão: tubo de ventilação versus aplicação tópica de mitomicina C

O uso do tubo de ventilação (TV) da orelha média, tratamento cirúrgico eleito da otite média com efusão (OME), não é isento de complicações, promovendo ainda limitação social pela necessidade de abandono dos banhos de imersão. A mitomicina C (MMC) é um antineoblástico, cuja aplicação tópica retarda a fibrose e previne a estenose cicatricial. Em cobaias, retardou o fechamento de timpanotomias, permitindo maior tempo de aeração da orelha média, à semelhança dos tubos de ventilação. FORMA DE ESTUDO: Clínico prospectivo. OBJETIVO: Comparar a eficácia entre timpanotomia, aspirado da efusão e inserção de tubo de ventilação (grupo TV) versus timpanotomia, aspirado da efusão e aplicação tópica de mitomicina C (grupo MMC). Comparar o tempo de manutenção da timpanotomia e a incidência de complicações nos dois grupos. RESULTADOS: O grupo MMC apresentou eficácia significativamente menor (52% versus 80%) que o grupo TV (p= 0,34). A presença de timpanometria tipo "B" e a ausência de comprometimento do óstio faríngeo tubário pelo tecido adenóide no pré-operatório representaram fatores de mau prognóstico. A aplicação tópica de MMC nas bordas da timpanotomia proporcionou um tempo de abertura da membrana timpânica por duas a três semanas. No grupo TV, a otorréia foi observada em 13,3% dos pacientes. No grupo MMC, apesar da menor eficácia, nenhum paciente apresentou complicações nem sofreu prolongada proibição dos banhos de imersão. CONCLUSÃO: Apesar de concluirmos que o TV apresenta maior eficácia, novos estudos utilizando maior concentração, maior tempo de aplicação ou o uso seriado de MMC no tratamento da otite média com efusão devem ser realizados.

Reduced influence of the ipsilateral ear on spatial tuning of auditory neurons in the albino superior colliculus: a knock-on effect of anomalies of the acoustic chiasm?

Auditory brainstem abnormalities affecting decussation patterns and nuclei involved in the acoustic chiasm exist in a variety of albino mammals, suggesting that binaural processes underlying spatial hearing may be disrupted in these mutants. To evaluate this we have compared the contribution of the two ears in albino and normally pigmented guinea pigs to the spatial tuning of auditory neurons in the deep layers of the superior colliculus (SC). Broadband noise stimuli at threshold and at suprathreshold intensities were presented from different azimuthal loudspeaker locations under free-field anechoic conditions, and auditory receptive fields were plotted before, during and after occluding the ipsilateral ear. We show that the deep layers of the albino SC contain a map of contralateral auditory azimuth along its anteroposterior axis, which is aligned with the visual map in the superficial layers above, just as in normal animals. We also show that threshold spatial responses are elicited only via the contralateral ear and at similar stimulus intensities (mean approximately 30 dB SPL) in the two pigmentation phenotypes. The mechanisms that maintain spatial tuning at sound intensities of 10-40 dB above threshold, however, differ markedly in these animals. Plugging the ipsilateral ear in normal guinea pigs caused significant expansions of their auditory receptive fields and loss of directional tuning, but in the albinos occlusion had little effect on these spatial properties. The results suggest that while spatial selectivity for relatively loud sounds among SC neurons is normally maintained via the binaural combination of contralateral excitatory drive and ipsilateral inhibition, it is achieved in albinos almost exclusively by monaural input from the contralateral ear. This finding is consistent with an excessive contralateral ear dominance of higher levels of the albino auditory system caused by anomalies of their acoustic chiasm, analogous to the monocular dominance of the visual system that results from excessive axon crossing at the optic chiasm in these animals.