RESUMEN
BACKGROUND: The tumor microenvironment (TME) plays an essential role in supporting and promoting tumor growth and progression. An inflammatory stroma is a widespread hallmark of the prostate TME, and prostate tumors are known to co-evolve with their reactive stroma. Cancer-associated fibroblasts (CAFs) within the reactive stroma play a salient role in secreting cytokines that contribute to this inflammatory TME. Although a number of inflammatory mediators have been identified, a clear understanding of key factors initiating the formation of reactive stroma is lacking. METHODS: We explored whether tumor secreted extracellular Hsp90 alpha (eHsp90α) may initiate a reactive stroma. Prostate stromal fibroblasts (PrSFs) were exposed to exogenous Hsp90α protein, or to conditioned medium (CM) from eHsp90α-expressing prostate cancer cells, and evaluated for signaling, motility, and expression of prototypic reactive markers. In tandem, ELISA assays were utilized to characterize Hsp90α-mediated secreted factors. RESULTS: We report that exposure of PrSFs to eHsp90 upregulates the transcription and protein secretion of IL-6 and IL-8, key inflammatory cytokines known to play a causative role in prostate cancer progression. Cytokine secretion was regulated in part via a MEK/ERK and NF-κB dependent pathway. Secreted eHsp90α also promoted the rapid and durable activation of the oncogenic inflammatory mediator signal transducer and activator of transcription (STAT3). Finally, eHsp90 induced the expression of MMP-3, a well-known mediator of fibrosis and the myofibroblast phenotype. CONCLUSIONS: Our results provide compelling support for eHsp90α as a transducer of signaling events culminating in an inflammatory and reactive stroma, thereby conferring properties associated with prostate cancer progression.
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Proteínas HSP90 de Choque Térmico/metabolismo , FN-kappa B/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata/metabolismo , Células del Estroma/metabolismo , Microambiente Tumoral/fisiología , Movimiento Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Proteínas HSP90 de Choque Térmico/genética , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Masculino , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , FN-kappa B/genética , Próstata/patología , Neoplasias de la Próstata/patología , Transducción de Señal , Células del Estroma/patologíaRESUMEN
BACKGROUND: Risks for methicillin-resistant Staphylococcus aureus (MRSA) among those with HIV infection have been found to vary, and the epidemiology of USA-300 community-acquired (CA) MRSA has not been adequately described. METHODS: We conducted a retrospective review of HIV-infected out-patients from January 2002 to December 2007 and employed multivariate logistic regression (MLR) to identify risks for MRSA colonization or infection. Pulsed-field gel electrophoresis (PFGE) was used to identify USA-300 strains. RESULTS: Seventy-two (8%) of 900 HIV-infected patients were colonized or infected with MRSA. MLR identified antibiotic exposure within the past year [odds ratio (OR) 3.4; 95% confidence interval (CI) 1.5-7.7] and nadir CD4 count <200 cells/microL (OR 2.5; 95% CI 1.2-5.3) as risks for MRSA colonization or infection. Receipt of antiretroviral therapy (ART) within the past year was associated with decreased risk (OR 0.16; 95% CI 0.07-0.4). Eighty-nine percent of available strains were USA-300. MLR identified skin or soft tissue infection (SSTI) as the only predictor for infection with USA-300 (OR 5.9; 95% CI 1.4-24.3). CONCLUSION: Significant risks for MRSA among HIV-infected patients were CD4 count nadir <200 cells/microL and antibiotic exposure. Only the presence of an SSTI was associated with having USA-300, and thus the use of patient characteristics to predict those with USA-300 was limited. In addition, ART within the previous year significantly reduced the risk of MRSA colonization or infection.
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Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Antibacterianos/uso terapéutico , Portador Sano/microbiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Cutáneas Estafilocócicas/microbiología , Adulto , Anciano , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Portador Sano/epidemiología , Comorbilidad , Electroforesis en Gel de Campo Pulsado , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Nariz/microbiología , Pacientes Ambulatorios , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/microbiología , Infecciones Cutáneas Estafilocócicas/epidemiología , Carga Viral , Adulto JovenRESUMEN
Auditory localization experiments typically either require subjects to judge the location of a sound source from a discrete set of response alternatives or involve measurements of the accuracy of orienting responses made toward the source location. To compare the results obtained by both methods, we trained ferrets by positive conditioning to stand on a platform at the center of a circular arena prior to stimulus presentation and then approach the source of a broadband noise burst delivered from 1 of 12 loudspeakers arranged at 30 degrees intervals in the horizontal plane. Animals were rewarded for making a correct choice. We also obtained a non-categorized measure of localization accuracy by recording head-orienting movements made during the first second following stimulus onset. The accuracy of the approach-to-target responses declined as the stimulus duration was reduced, particularly for lateral and posterior locations, although responses to sounds presented in the frontal region of space and directly behind the animal remained quite accurate. Head movements had a latency of approximately 200 ms and varied systematically in amplitude with stimulus direction. However, the final head bearing progressively undershot the target with increasing eccentricity and rarely exceeded 60 degrees to each side of the midline. In contrast to the approach-to-target responses, the accuracy of the head orienting responses did not change much with stimulus duration, suggesting that the improvement in percent correct scores with longer stimuli was due, at least in part, to re-sampling of the acoustical stimulus after the initial head turn had been made. Nevertheless, for incorrect trials, head orienting responses were more closely correlated with the direction approached by the animals than with the actual target direction, implying that at least part of the neural circuitry for translating sensory spatial signals into motor commands is shared by these two behaviors.
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Vías Auditivas/fisiología , Orientación , Localización de Sonidos/fisiología , Estimulación Acústica/métodos , Análisis de Varianza , Animales , Conducta Animal , Hurones , Movimientos de la Cabeza , Psicofísica , Factores de TiempoRESUMEN
Two experiments were conducted to evaluate the effects of feeding different levels of wet corn gluten feed (WCGF) and dietary roughage on performance, carcass characteristics, and feeding behavior of feedlot cattle fed diets based on steam-flaked corn (SFC). In Exp. 1, crossbred steers (n = 200; BW = 314 kg) were fed 4 dietary treatments (DM basis): a standard SFC-based diet containing 9% roughage (CON) and 3 SFC-based diets containing 40% WCGF, with either 9, 4.5, or 0% roughage. A linear (P = 0.04) increase in final BW and DMI (P < 0.01) was observed in diets containing WCGF as dietary roughage increased. Steers fed WCGF and higher levels of roughage had greater (P = 0.01) ADG than steers fed lower levels of roughage. Steers fed the CON diet had lower (P = 0.04) daily DMI and greater (P = 0.03) G:F than those fed WCGF. Most carcass characteristics of steers fed CON did not differ (P > 0.10) from those of steers fed WCGF. Based on feed disappearance and visual scan data, consumption rate did not differ (P > 0.10) among treatments; however, feeding intensity (animals present at the bunk after feeding) was greater for steers fed CON (P < 0.01) than for steers fed WCGF. In Exp. 2, yearling crossbred steers (n = 1,983; BW = 339 kg) were fed 4 dietary treatments (DM basis): a standard SFC-based control diet that contained 9% roughage (CON) and 3 SFC-based diets containing either 20% WCGF and 9% roughage or 40% WCGF with 9 or 4.5% roughage. Steers fed the CON diet tended to have lower final BW (P = 0.14), ADG (P = 0.01), and DMI (P < 0.01) than steers fed diets containing WCGF. Steers fed the 20% WCGF diet had greater (P = 0.08) G:F than steers fed the 40% WCGF diets. With 40% WCGF, increasing roughage from 4.5 to 9% decreased (P < 0.01) G:F and increased (P = 0.06) DMI. Gain efficiency was improved (P < 0.01) for steers fed CON vs. those fed diets containing WCGF, whereas HCW (P = 0.02) and dressing percentage (P < 0.01) were greater for steers fed WCGF. Percentage of cattle grading USDA Choice was greater (P = 0.02) for cattle fed WCGF. Results suggest that replacing SFC with up to 40% WCGF increased ADG and decreased G:F when 4.5 to 9.0% roughage was supplied. More CON steers were present at the feed bunk during the first hour after feeding than WCGF steers, suggesting that including WCGF at 40% of the diet affected feeding behavior.
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Alimentación Animal/análisis , Bovinos/crecimiento & desarrollo , Fibras de la Dieta/administración & dosificación , Glútenes/administración & dosificación , Zea mays , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Composición Corporal/efectos de los fármacos , Composición Corporal/fisiología , Bovinos/metabolismo , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos , Ingestión de Energía , Metabolismo Energético , Masculino , Distribución Aleatoria , Aumento de PesoRESUMEN
Two experiments were conducted to evaluate receiving-period performance, morbidity, and humoral immune response, as well as finishing performance and carcass characteristics of heifers fed different sources of supplemental Zn. In Exp. 1, 97 crossbred beef heifers (initial BW = 223.4 kg) were fed a 65% concentrate diet with no supplemental Zn (control) or 75 mg of supplemental Zn/kg of DM from Zn sulfate, Zn methionine, or Zn propionate. During a 35-d receiving period, heifers were monitored daily for signs of bovine respiratory disease. Serum samples were collected for Zn analysis on d 0, 14, and 28. After the receiving period, heifers were adapted to and fed a high-concentrate diet with no supplemental Zn for 42 d. Heifers were then assigned to finishing diet treatments, with the same concentrations and sources of supplemental Zn as during the receiving period and fed for an average of 168 d. Serum samples also were obtained on d 0 and 56 of the finishing period and at the end of the study. During the receiving period, control heifers had a greater (P < or = 0.05) BW and G:F on d 35 than heifers in the other treatments, but no differences were observed among treatments for morbidity or serum Zn concentrations (P > or = 0.50). For the finishing period, DMI and ADG did not differ among treatments; however, overall G:F tended (P = 0.06) to be less for control heifers than for heifers in the 3 supplemental Zn treatments. On d 56 of the finishing period, control heifers tended (P = 0.06) to have a lower serum Zn concentration than heifers in the 3 supplemental Zn treatments. In Exp. 2, 24 crossbred beef heifers (initial BW = 291.1 kg) were fed the same 4 treatments as in Exp. 1 for a 21-d period. The humoral immune response to treatments was determined by measuring specific antibody titers after s.c. injection of ovalbumin on d 0 and 14. Body weights and blood samples for serum Zn concentration and ovalbumin IgG titers were collected on d 0, 7, 14, and 21. Serum Zn concentration and specific ovalbumin IgG titers did not differ (P > 0.10) among the 4 treatments on any sampling day. Results from these 2 studies showed no major differences among the sources of supplemental Zn for receiving period morbidity, ADG, DMI, and humoral immune response of beef heifers; however, a lack of supplemental Zn during an extended finishing period tended to negatively affect G:F.
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Formación de Anticuerpos/efectos de los fármacos , Bovinos/crecimiento & desarrollo , Ingestión de Energía , Aumento de Peso/efectos de los fármacos , Zinc/farmacología , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bovinos/inmunología , Enfermedades de los Bovinos/inmunología , Suplementos Dietéticos , Femenino , Ovalbúmina/inmunología , Distribución Aleatoria , Enfermedades Respiratorias/inmunología , Enfermedades Respiratorias/veterinaria , Oligoelementos/sangre , Oligoelementos/farmacología , Zinc/sangreRESUMEN
Two experiments were conducted to evaluate the effects of Cu and Zn source on performance, morbidity, and humoral immune response in lightweight, newly received beef heifers. A 2 x 2 factorial arrangement of treatments was used in both experiments, with either a sulfate or a polysaccharide mineral complex (SQM) source of both Cu and Zn as the factors. Supplemental Cu and Zn were included in the receiving diet at concentrations designed to provide 10 mg of Cu/kg and 75 mg of Zn/kg (DM basis). In Exp. 1, 219 newly received beef heifers (British x Continental, average initial BW = 208 kg) were given ad libitum access to a 65% concentrate diet for 35 d to determine treatment effects on DMI, ADG, G:F, and bovine respiratory disease (BRD) morbidity. In Exp. 2, 24 heifers (average initial BW = 272 kg) were fed a diet with no supplemental Cu or Zn for 35 d, followed by fasting-refeeding-fasting stress, after which the same treatment diets used in Exp. 1 were fed for 21 d to examine the effects on humoral immune response (plasma IgG titer determined by ELISA on d 7, 14, and 21) to an ovalbumin (OVA) vaccine given on d 0 and 14. Copper source x Zn source interactions were not detected in either experiment. In Exp. 1, neither Cu nor Zn source affected (P > 0.10) DMI, ADG, G:F, or BRD morbidity. In Exp. 2, d 14 (P = 0.02) and 21 (P = 0.06) OVA titers were greater for heifers that received SQM Zn compared with heifers receiving ZnSO4, but heifers receiving CuSO4 had greater OVA titers than did heifers on the SQM Cu treatment on d 14 (P = 0.01) and 21 (P = 0.001). In summary, neither supplemental Cu nor Zn source affected performance or morbidity of lightweight, newly received heifers; however, source of both Cu or Zn affected the humoral immune response to OVA, although source effects were not consistent for the two minerals.
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Enfermedades de los Bovinos/inmunología , Bovinos/crecimiento & desarrollo , Bovinos/inmunología , Cobre/administración & dosificación , Enfermedades Respiratorias/veterinaria , Zinc/administración & dosificación , Animales , Formación de Anticuerpos/efectos de los fármacos , Cobre/farmacología , Sulfato de Cobre/administración & dosificación , Sulfato de Cobre/farmacología , Interacciones Farmacológicas , Ingestión de Alimentos/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Polisacáridos/administración & dosificación , Polisacáridos/farmacología , Distribución Aleatoria , Enfermedades Respiratorias/inmunología , Aumento de Peso/efectos de los fármacos , Zinc/farmacología , Óxido de Zinc/administración & dosificación , Óxido de Zinc/farmacologíaRESUMEN
Three experiments were conducted to evaluate the effects of roughage source and concentration on intake and performance by finishing heifers. In Exp. 1, 12 medium-framed beef heifers (average BW = 389 kg) were used in three simultaneous 4 x 4 Latin square intake trials to evaluate the effects of dietary NDF supply from alfalfa hay, sudan hay, wheat straw, or cottonseed hulls fed in each Latin square at 5, 10, or 15% of dietary DM. Within each roughage concentration, roughage NDF accounted for the majority of variation in NEg intake/kg of BW0.75 among the roughage sources. Averaged across roughage concentrations, NEg intake/kg of BW0.75 tended to be greater (P < 0.10) when heifers were fed cottonseed hulls, sudan hay, or wheat straw than when they were fed alfalfa. In Exp. 2, six medium-framed beef heifers (average BW = 273 kg) were used in a 3 x 3 Latin square design to determine whether diets containing 10% (DM basis) alfalfa, cottonseed hulls, or sudan silage differed in eating rate. Average DM eating rates did not differ (P > 0.10) among roughage sources, which we interpreted to suggest that 90% concentrate diets containing alfalfa, cottonseed hulls, and sudan silage do not differ in the amount of chewing required during eating. In Exp. 3, 105 medium-framed beef heifers (average BW = 275 kg) were used in a 140-d finishing trial to evaluate three methods of dietary roughage exchange. Alfalfa at 12.5% of the dietary DM (ALF12.5) was used as a standard, and cottonseed hulls and sudan silage were each fed at three different levels: exchanged with ALF12.5 on an equal percentage DM basis, an equal NDF basis, or an equal NDF basis, where only NDF from particles larger than 2.36 mm (retained NDF) were considered to contribute to the NDF. No differences (P > 0.10) in ADG, DMI, gain:feed ratio, or NEg intake/kg of BW0.75 were detected between alfalfa and cottonseed hulls exchanged on an equal NDF basis. For sudan silage, exchanging with ALF12.5 on an equal retained NDF basis resulted in no differences (P > 0.10) in ADG, DMI, or NEg intake/kg of BW0.75. These data provide a preliminary indication that depending on the roughage sources evaluated, roughage NDF content and(or) roughage NDF from particles larger than 2.36 mm might provide a useful index of roughage value in high-concentrate finishing diets.
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Alimentación Animal/análisis , Bovinos/crecimiento & desarrollo , Fibras de la Dieta/administración & dosificación , Ingestión de Energía , Crianza de Animales Domésticos/métodos , Animales , Composición Corporal , Bovinos/metabolismo , Fibras de la Dieta/metabolismo , Ingestión de Energía/fisiología , Femenino , Masticación , Tamaño de la Partícula , EnsilajeRESUMEN
The location of a sound source is derived by the auditory system from spatial cues present in the signals at the two ears. These cues include interaural timing and level differences, as well as monaural spectral cues generated by the external ear. The values of these cues vary with individual differences in the shape and dimensions of the head and external ears. We have examined the neurophysiological consequences of these intersubject variations by recording the responses of neurons in ferret primary auditory cortex to virtual sound sources mimicking the animal's own ears or those of other ferrets. For most neurons, the structure of the spatial response fields changed significantly when acoustic cues measured from another animal were presented. This is consistent with the finding that humans localize less accurately when listening to virtual sounds from other subjects. To examine the role of experience in shaping the ability to localize sound, we have studied the behavioural consequences of altering binaural cues by chronically plugging one ear. Ferrets raised and tested with one ear plugged learned to localize as accurately as control animals, which is consistent with previous findings that the representation of auditory space in the midbrain can accommodate abnormal sensory cues during development. Adaptive changes in behaviour were also observed in adults, particularly if they were provided with regular practice in the localization task. Together, these findings suggest that the neural circuits responsible for sound localization can be recalibrated throughout life.
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Corteza Auditiva/fisiología , Plasticidad Neuronal/fisiología , Percepción Espacial/fisiología , Animales , Humanos , Localización de Sonidos/fisiología , Colículos Superiores/fisiologíaRESUMEN
Conductive hearing loss produced by middle ear disease (MED) is very prevalent in the first 5 years of childhood. Both MED in children and prolonged ear plugging in animals lead to a binaural hearing impairment that persists beyond the duration of the peripheral impairment. However, after cessation of the MED, or removal of the ear plug, binaural hearing gradually improves. We suggest here that this improvement is a passive form of auditory learning. We also show that active auditory learning, through repetition of discrimination tasks, can accelerate performance increments, both after hearing loss and in unimpaired individuals. A more detailed understanding of auditory learning holds out the prospect of improving rehabilitation strategies for the language- and hearing-impaired.
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Corteza Auditiva/fisiopatología , Pérdida Auditiva Central/fisiopatología , Pérdida Auditiva Central/rehabilitación , Pérdida Auditiva Conductiva/fisiopatología , Pérdida Auditiva Conductiva/rehabilitación , Umbral Auditivo/fisiología , Niño , Pérdida Auditiva Bilateral/etiología , Pérdida Auditiva Bilateral/fisiopatología , Pérdida Auditiva Bilateral/rehabilitación , Pérdida Auditiva Central/etiología , Pérdida Auditiva Conductiva/etiología , Humanos , Otitis Media/complicaciones , Enmascaramiento Perceptual/fisiología , Percepción del Habla/fisiologíaRESUMEN
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.
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Corteza Auditiva/fisiología , Plasticidad Neuronal , Adaptación Fisiológica , Animales , Audición/fisiología , Mamíferos/fisiologíaRESUMEN
Filial imprinting in the domestic chick occurs during a sensitive period of development. The exact timing of this period can vary according to the methods used to measure imprinting. Using our imprinting paradigm, we have shown that normal, dark-reared chicks lose the ability to imprint after the second day post-hatching. Further, we reported that chicks treated 10 h after hatching with a mixture of the noncompetitive NMDA receptor antagonist ketamine (55 mg/kg) and the alpha(2)-adrenergic receptor agonist xylazine (6 mg/kg) were able to imprint on day 8 after hatching, whereas controls treated with saline did not imprint. We now show that the effect of the ketamine-xylazine mixture can be mimicked by treating chicks with ketamine alone or with another noncompetitive NMDA receptor antagonist, MK-801 (5 mg/kg). Treating chicks with a single dose of ketamine (55 mg/kg) or with a single dose of xylazine (6 mg/kg) failed to produce the effect on the sensitive period. However, prolonging the action of ketamine by treating chicks with two doses of ketamine (at 10 and 12 h after hatching) did allow imprinting on day 8. In contrast, prolonging the action of xylazine had no effect on the sensitive period for imprinting. Chicks treated with MK-801 were also able to imprint on day 8. Thus, we have evidence that the NMDA receptor system is involved in the mechanisms that control the sensitive period for imprinting.
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Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Impronta Psicológica/efectos de los fármacos , Ketamina/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Agonistas alfa-Adrenérgicos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Pollos , Oscuridad , Relación Dosis-Respuesta a Droga , Impronta Psicológica/fisiología , Luz , Xilazina/farmacologíaRESUMEN
We have examined the effects on auditory spatial acuity in the horizontal plane of depriving ferrets of patterned visual cues by binocular eyelid suture in infancy or for a comparable period in adulthood. Minimum audible angles (MAAs) were measured for 500-, 100- and 40-ms broadband noise bursts at the midline and at 45 degrees to one side. A logistic regression analysis revealed no consistent difference between the midline MAAs of normal and infant lid-sutured ferrets. However, the lateral field MAAs of the infant-deprived group were significantly smaller and showed less inter-subject variability than those of normal-sighted ferrets. The animals deprived in adulthood were tested in the lateral field only, firstly 6 months after binocular eyelid suture and again after a further 10 months. For the first test, the MAAs achieved by these animals with 500- and 100-ms noise bursts were significantly smaller than the normal values and no different from those of the infant-deprived group. A significant improvement in performance at the two shortest stimulus durations (100 and 40 ms) was observed when the adult-deprived animals were re-tested. Their second-test MAAs did not differ from those of the infant-deprived group at any of the three stimulus durations used, and both groups achieved significantly better scores than the normal-sighted control animals. These results show that prolonged visual deprivation in both juvenile and adult ferrets can lead to a significant improvement in auditory spatial acuity in the lateral sound field. This is consistent with reports that congenitally blind humans can localize peripheral sounds more accurately than normal controls.
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Umbral Auditivo/fisiología , Localización de Sonidos/fisiología , Estimulación Acústica , Animales , Señales (Psicología) , Hurones , Movimientos de la Cabeza , Aprendizaje , Tiempo de Reacción , Análisis de Regresión , Privación Sensorial , Percepción VisualRESUMEN
We investigated the behavioral consequences of removing the pinna and concha of the external ear bilaterally in infancy on the sound localization ability of adult ferrets. Altering spectral cues in this manner has previously been shown to disrupt the development of the neural representation of auditory space in the superior colliculus. Using broadband noise stimuli, we tested pinnae-removed ferrets and normal ferrets in three sound localization tasks. In each case, we found that both groups of animals performed significantly better when longer duration noise bursts were used. In a relative localization task, we measured the acuity with which the ferrets could discriminate between two speakers in the horizontal plane. The speakers were placed symmetrically either around the anterior midline or around a position 45 degrees lateral to the midline. In this task, the pinnae-removed ferrets achieved very similar scores to the normal ferrets. By contrast, in another relative localization task that measured localization ability in the midsagittal plane, pinnae-removed ferrets performed less well than normals. In an absolute localization task, 12 speakers were spaced at 30 degrees intervals in the horizontal plane at the level of the ferrets' ears. Overall, the pinnae-removed ferrets also performed poorly in this task compared with normal ferrets: they made significantly fewer correct responses, larger localization errors and more front-back errors. Both normal and pinnae-removed animals showed an improvement in performance with practice, although the pattern of improvement differed for each group. The largest improvements in localization accuracy were achieved by the pinnae-removed ferrets, particularly at the frontal positions, and their performance eventually approached that of the normal animals. Nevertheless, some intergroup differences were still present. In particular, the pinnae-removed ferrets continued to make significantly more front-back errors than the normals. These deficits can be attributed to differences in the spectral localization cues available to the animals. Acoustical measurements showed that, compared with normal animals, the head-related transfer functions in the horizontal plane were largely ambiguous around the interaural axis and also contained fewer location-dependent features in the midsagittal plane.
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Envejecimiento/fisiología , Vías Auditivas/fisiología , Tronco Encefálico/fisiología , Señales (Psicología) , Neuronas/fisiología , Localización de Sonidos/fisiología , Estimulación Acústica , Animales , Percepción Auditiva/fisiología , Oído Externo , Femenino , Hurones , Masculino , Percepción Espacial , Colículos Superiores/fisiologíaRESUMEN
Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7-15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90 degrees to the right, that was masked by two sources of broad-band noise. In one condition ("control"), both noise sources were 90 degrees right and, in the second condition ("bilateral"), one noise source was moved to 90 degrees left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.
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Percepción Auditiva/fisiología , Pérdida Auditiva Conductiva/fisiopatología , Audición/fisiología , Estimulación Acústica , Animales , Hurones , Lateralidad Funcional , SonidoRESUMEN
Precocial animals, such as the chick, exhibit a form of learning termed filial imprinting. The chick's sensitive period for filial imprinting is restricted to the first few days after hatching. The neural mechanism that terminates the sensitive period is not fully understood. It is thought to be an experience-dependent event because once a chick has imprinted, it will not readily imprint on another stimulus. However, even dark-reared chicks eventually lose the ability to imprint, which suggests that the ending of the sensitive period may not be entirely experience-dependent. The present study investigates factors that may contribute to the ending of the sensitive period. In our experiments, dark-reared chicks were unable to imprint after Day 2 posthatching, but chicks treated 10 h after hatching with an intramuscular injection of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (55 mg/kg) and the alpha2-adrenoceptor agonist xylazine (6 mg/kg) (KX) imprinted on a stuffed hen 8 days after hatching. Similarly treated chicks did not imprint on a red and black box, although the box was an effective imprinting stimulus for Day 2 chicks. Chicks treated with KX at 20 or 40 h posthatching or on Day 4 or 7 as well as controls treated with pyrogen-free saline were unable to imprint on Day 8.
Asunto(s)
Pollos/fisiología , Impronta Psicológica/efectos de los fármacos , Agonistas alfa-Adrenérgicos/farmacología , Envejecimiento/psicología , Animales , Animales Recién Nacidos , Oscuridad , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Ketamina/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Xilazina/farmacologíaRESUMEN
We report a role for the tectal and posterior commissural system (TC/PC) in functional lateralization of the chicken brain. Unlike the corpus callosum of mammals which is thought to generate lateralization, the TC/PC in the chicken brain is shown to suppress lateralization. The TC/PC was sectioned on day 2 post-hatching. The performance of this TC/PC-sectioned group on a battery of monocular, behavioural tests was compared to a sham-lesioned group and an untreated group. The first of these tests measured pecking and fear responses to a small bead. In both the sham-lesioned group and the untreated group there was no change in the pecking response over repeated presentations of the bead, nor was there a left eye/right eye difference in either of these groups. In contrast, the TC/PC-sectioned group showed increased pecking of the bead each time it was presented. This increase in the pecking response was significantly greater for those chicks tested using the right eye than for those tested using the left eye. That is, sectioning the TC/PC caused a lateralized response which was not seen in either of the control groups, demonstrating that the intact TC/PC suppresses lateralization at the tectal level. In the other tasks (latency to peck at a mealworm and a visual discrimination learning task) the untreated controls showed clear left eye/right eye differences while the sham-lesioned group and the TC/PC-sectioned group showed no lateralization. It is suggested that for these two tasks the loss of lateralization is due to lesioning an area in the midbrain but not to sectioning the TC/PC.