RESUMEN

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17ß-estradiol (E2), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E2-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E2-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E2-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E2-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.

Asunto(s)

Cóclea , Estradiol/farmacología , Potenciales Evocados Auditivos/efectos de los fármacos , Pérdida Auditiva Provocada por Ruido , Animales , Cóclea/metabolismo , Cóclea/patología , Cóclea/fisiopatología , Femenino , Pérdida Auditiva Provocada por Ruido/metabolismo , Pérdida Auditiva Provocada por Ruido/patología , Pérdida Auditiva Provocada por Ruido/fisiopatología , Pérdida Auditiva Provocada por Ruido/prevención & control , Ratones , Ovariectomía

RESUMEN

Noise-induced hearing loss (NIHL) results from a complex interplay of damage to the sensory cells of the inner ear, dysfunction of its lateral wall, axonal retraction of type 1C spiral ganglion neurons, and activation of the immune response. We use RiboTag and single-cell RNA sequencing to survey the cell-type-specific molecular landscape of the mouse inner ear before and after noise trauma. We identify induction of the transcription factors STAT3 and IRF7 and immune-related genes across all cell-types. Yet, cell-type-specific transcriptomic changes dominate the response. The ATF3/ATF4 stress-response pathway is robustly induced in the type 1A noise-resilient neurons, potassium transport genes are downregulated in the lateral wall, mRNA metabolism genes are downregulated in outer hair cells, and deafness-associated genes are downregulated in most cell types. This transcriptomic resource is available via the Gene Expression Analysis Resource (gEAR; https://umgear.org/NIHL) and provides a blueprint for the rational development of drugs to prevent and treat NIHL.

Asunto(s)

Oído Interno/metabolismo , Células Ciliadas Auditivas/metabolismo , Pérdida Auditiva Provocada por Ruido/metabolismo , Pérdida Auditiva Provocada por Ruido/fisiopatología , Ganglio Espiral de la Cóclea/metabolismo , Animales , Cóclea/metabolismo , Cóclea/fisiopatología , Oído Interno/fisiopatología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva Provocada por Ruido/genética , Ratones , Neuronas/metabolismo , Ruido , Ganglio Espiral de la Cóclea/citología , Ganglio Espiral de la Cóclea/fisiopatología

RESUMEN

CONTEXT: Sound levels in fitness classes often exceed safe levels despite studies that show many participants find high sound levels stressful. AIMS: The objective is to determine if lower sound levels in spinning classes significantly impact exercise intensity and to determine if class participants prefer the music played at lower levels. SETTINGS AND DESIGN: Observational study of 1-hour group spin classes. METHODS AND MATERIALS: Sound levels were measured in 18 spin classes over two weeks. No adjustments were made in week-1 and sound levels were decreased by 3 dB in week-2. Participant preferences and data on post-class hearing changes were collected via post-class questionnaires (n = 213) and divided into three terciles based on the total sound exposure of corresponding classes. STATISTICAL ANALYSIS USED: Unweighted survey generalized linear models are used to sort the causal relationships between different variables simultaneously and participant responses. The Chi-square test is used to reveal statistically significant relationships between two or more categorical variables. RESULTS: When mean sound levels exceeded 98.4 dBC, respondents were 23 times more likely to report the music as too loud than too quiet (P < 0.05), and four times more likely to prefer a decrease, rather than an increase, in sound level (P < 0.05). There was no significant difference in respondents reporting high exercise intensity between the middle (95.7-98.1 dBC) and upper (98.4-101.0 dBC) terciles, 67.1% and 71.8%, respectively (P = 0.53). Overall, 25.9% of respondents reported auditory symptoms following classes. Analysis in the context of dBA and dBC produced congruent conclusions and interpretations. CONCLUSIONS: Sound levels in many fitness classes remain dangerously high. However, music level can be lowered without a significant impact on perceived exercise intensity and many participants prefer lower sound levels than current levels.

Asunto(s)

Ciclismo/psicología , Ejercicio Físico/psicología , Pérdida Auditiva Provocada por Ruido/psicología , Música/psicología , Ruido/efectos adversos , Adulto , Umbral Auditivo , Femenino , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/etiología , Humanos , Masculino , Percepción , Sonido

RESUMEN

Cochlear damage is often thought to result in hearing thresholds shift, whether permanent or temporary. The report of tinnitus in the absence of any clear deficit in cochlear function was believed to indicate that hearing loss and tinnitus, while comorbid, could arise independently from each other. In all likelihood, tinnitus that is not of central nervous system origin is associated with hearing loss. As a correlate, although a treatment of most forms of tinnitus will likely emerge in the years to come, curing tinnitus will first require curing hearing loss.

Asunto(s)

Cóclea/fisiopatología , Potenciales Evocados Auditivos del Tronco Encefálico , Pérdida Auditiva Provocada por Ruido/etiología , Ruido/efectos adversos , Acúfeno/etiología , Estimulación Acústica , Umbral Auditivo , Audición , Pérdida Auditiva Provocada por Ruido/diagnóstico , Pérdida Auditiva Provocada por Ruido/fisiopatología , Humanos , Acúfeno/diagnóstico , Acúfeno/fisiopatología

Asunto(s)

Acúfeno/diagnóstico , Acúfeno/terapia , Audiología , Audífonos , Humanos

RESUMEN

Hearing loss is the most common form of sensory impairment in humans, with an anticipated rise in incidence as the result of recreational noise exposures. Hearing loss is also the second most common health issue afflicting military veterans. Currently, there are no approved therapeutics to treat sensorineural hearing loss in humans. While hearing loss affects both men and women, sexual dimorphism is documented with respect to peripheral and central auditory physiology, as well as susceptibility to age-related and noise-induced hearing loss. Physiological differences between the sexes are often hormone-driven, and an increasing body of literature demonstrates that the hormone estrogen and its related signaling pathways may in part, modulate the aforementioned differences in hearing. From a mechanistic perspective, understanding the underpinnings of the hormonal modulation of hearing may lead to the development of therapeutics for age related and noise induced hearing loss. Here the authors review a number of studies that range from human populations to animal models, which have begun to provide a framework for understanding the functional role of estrogen signaling in hearing, particularly in normal and aberrant peripheral auditory physiology.

Asunto(s)

Umbral Auditivo/fisiología , Estrógenos/metabolismo , Pérdida Auditiva Provocada por Ruido/fisiopatología , Audición/fisiología , Caracteres Sexuales , Percepción Auditiva , Sordera/fisiopatología , Pérdida Auditiva Sensorineural/fisiopatología , Pruebas Auditivas/métodos , Humanos , Masculino , Ruido

RESUMEN

BACKGROUND: Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice. METHODS: Here we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.3 kHz). Hearing was assessed by measuring auditory brainstem responses (ABR) at 8, 16, 24, and 32 kHz, 1 week before, as well as at 24 h and 15-21 days following exposure (baseline, compound threshold shift (CTS) and permanent threshold shift (PTS), respectively), followed by histologic analyses. RESULTS: We found significant differences in the CTS and PTS of the control (vehicle injected) mice to noise, where females had a significantly smaller CTS at 16 and 24 kHz (p < 0.0001) and PTS at 16, 24, and 32 kHz (16 and 24 kHz p < 0.001, 32 kHz p < 0.01). This sexual dimorphic effect could not be explained by a differential loss of sensory cells or synapses but was reflected in the amplitude and amplitude progression of wave I of the ABR, which correlates with outer hair cell (OHC) function. Finally, the frequency of the protective effect of SAHA differed significantly between males (PTS, 24 kHz, p = 0.002) and females (PTS, 16 kHz, p = 0.003), and the magnitude of the protection was smaller in females than in males. Importantly, the magnitude of the protection by SAHA was smaller than the effect of sex as a biological factor in the vehicle-injected mice. CONCLUSIONS: These results indicate that female mice are significantly protected from NIHL in comparison to males and that therapeutics for NIHL may have a different effect in males and females. The data highlight the importance of analyzing NIHL experiments from males and females, separately. Finally, these data also raise the possibility of effectors in the estrogen signaling pathway as novel therapeutics for NIHL.

Asunto(s)

Pérdida Auditiva Provocada por Ruido/prevención & control , Ruido/efectos adversos , Sustancias Protectoras/farmacología , Caracteres Sexuales , Vorinostat/farmacología , Animales , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Masculino , Ratones

RESUMEN

Maintaining the vitality of the dental pulp, the highly innervated and highly vascular, innermost layer of the tooth, is a critical goal of any dental procedure. Upon injury, targeting the pulp with specific therapies is challenging because it is encased in hard tissues. This project describes a method that can effectively deliver therapeutic agents to the pulp. This method relies on the use of nanoparticles that can be actively steered using magnetic forces to the pulp, traveling through naturally occurring channels in the dentin (the middle layer of the tooth). This method can reduce the inflammation of injured pulp and improve the penetration of dental adhesives into dentin. Such a delivery method would be less expensive, and both less painful and less traumatic than existing therapeutic options available for treatment of injured dental pulp. This technique would be simple and could be readily translated to clinical use.

Asunto(s)

Antiinflamatorios/administración & dosificación , Pulpa Dental/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Inflamación/tratamiento farmacológico , Nanopartículas de Magnetita/administración & dosificación , Prednisolona/administración & dosificación , Enfermedades Estomatognáticas/tratamiento farmacológico , Animales , Antiinflamatorios/química , Femenino , Nanopartículas de Magnetita/química , Masculino , Prednisolona/química , Ratas , Ratas Long-Evans

RESUMEN

Delivery of therapy to the cochlea is a challenge and limits the efficacy of therapies meant to treat hearing loss, reverse tinnitus, and protect hearing from chemotherapy regimens. Magnetic injection is a technique that uses magnetic fields to inject nanoparticles from the middle ear into the cochlea, where they can then elute therapy to treat hearing disorders. To evaluate the safety of this treatment in the middle ear, 30 rats were subdivided into 6 groups and treated by single or multiple intratympanic injections of saline, prednisolone, nanoparticles, or nanoparticles loaded with prednisolone. A specially designed magnet array was used to magnetically inject the particles from the middle ear to the cochlea. Treatment began at study day 0, and animals were euthanized on study day 2, 30, or 90. Temporal bones were collected and prepared for histopathological examination. Intratympanic administration of magnetic nanoparticles and/or prednisolone resulted in minimal to mild inflammatory changes in all treated groups. The incidence and severity of the inflammatory changes observed appeared slightly increased in animals administered nanoparticles, with or without prednisolone, when compared to animals administered prednisolone alone. At study day 90, there was partial reversibility of the findings noted at study day 2 and 30. Repeat administration did not appear to cause greater inflammatory changes.

Asunto(s)

Antiinflamatorios/administración & dosificación , Cóclea , Sistemas de Liberación de Medicamentos/métodos , Fenómenos Magnéticos , Nanopartículas/administración & dosificación , Prednisolona/administración & dosificación , Animales , Compuestos Férricos/administración & dosificación , Masculino , Ratas , Ratas Long-Evans

RESUMEN

Cisplatin (cis-diamminedichloroplatinum) is widely used as a chemotherapeutic drug for genitourinary, breast, lung and head and neck cancers. Though effective in inducing apoptosis in cancer cells, cisplatin treatment causes severe hearing loss among patients. Steroids have been shown to mitigate cisplatin-induced hearing loss. However, steroids may interfere with the anti-cancer properties of cisplatin if administered systemically, or are rapidly cleared from the middle and inner ear and hence lack effectiveness when administered intra-tympanically. In this work, we deliver prednisolone-loaded nanoparticles magnetically to the cochlea of cisplatin-treated mice. This magnetic delivery method substantially reduced hearing loss in treated animals at high frequency compared to control animals or animals that received intra-tympanic methylprednisolone. The method also protected the outer hair cells from cisplatin-mediated ototoxicity.

RESUMEN

Objectives To update the medical literature on recent cellular and molecular advances in otitis media disease models with a principal focus on developments in the past 5 years. We also aim to explain recent translational advances in cellular and molecular biology that have influenced our understanding and management of otitis media. Data Sources PubMed-indexed peer-reviewed articles. Review Methods A comprehensive review of the literature was conducted with the term otitis media and the following search terms: molecular biology, cell biology, innate immunity, oxidative stress, mucins, molecular diagnostics. Included articles were published in the English language from January 1, 2010, to July 31, 2015. Implications for Practice The molecular understanding of otitis media disease progression has rapidly advanced over the last 5 years. The roles of inflammation, mucins, and cell signaling mechanisms have been elucidated and defined. Advances in the field provide a plethora of opportunities for innovative molecular targeting in the development of novel therapeutic strategies for otitis media.

Asunto(s)

Otitis Media , Animales , Congresos como Asunto , Progresión de la Enfermedad , Sistemas de Liberación de Medicamentos , Predisposición Genética a la Enfermedad , Inmunidad Innata , Otitis Media/diagnóstico por imagen , Otitis Media/tratamiento farmacológico , Otitis Media/inmunología , Otitis Media/fisiopatología , Transducción de Señal , Tomografía de Coherencia Óptica

RESUMEN

This article presents a method to investigate how magnetic particle characteristics affect their motion inside tissues under the influence of an applied magnetic field. Particles are placed on top of freshly excised tissue samples, a calibrated magnetic field is applied by a magnet underneath each tissue sample, and we image and quantify particle penetration depth by quantitative metrics to assess how particle sizes, their surface coatings, and tissue resistance affect particle motion. Using this method, we tested available fluorescent particles from Chemicell of four sizes (100 nm, 300 nm, 500 nm, and 1 µm diameter) with four different coatings (starch, chitosan, lipid, PEG/P) and quantified their motion through freshly excised rat liver, kidney, and brain tissues. In broad terms, we found that the applied magnetic field moved chitosan particles most effectively through all three tissue types (as compared to starch, lipid, and PEG/P coated particles). However, the relationship between particle properties and their resulting motion was found to be complex. Hence, it will likely require substantial further study to elucidate the nuances of transport mechanisms and to select and engineer optimal particle properties to enable the most effective transport through various tissue types under applied magnetic fields.

RESUMEN

Magnetic nanoparticles (MNPs) have been used as effective vehicles for targeted delivery of theranostic agents in the brain. The advantage of magnetic targeting lies in the ability to control the concentration and distribution of therapy to a desired target region using external driving magnets. In this study, we investigated the behavior and safety of MNP motion in brain tissue. We found that MNPs move and form nanoparticle chains in the presence of a uniform magnetic field, and that this chaining is influenced by the applied magnetic field intensity and the concentration of MNPs in the tissue. Using electrophysiology recordings, immunohistochemistry and fluorescent imaging we assessed the functional health of neurons and neural circuits and found no adverse effects associated with MNP motion through brain tissue. FROM THE CLINICAL EDITOR: Much research has been done to test the use of nanocarriers for gaining access across the blood brain barrier (BBB). In this respect, magnetic nanoparticles (MNPs) are one of the most studied candidates. Nonetheless, the behavior and safety of MNP once inside brain tissue remains unknown. In this article, the authors thus studied this very important subject.

Asunto(s)

Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/efectos adversos , Nanopartículas de Magnetita/administración & dosificación , Neuronas/efectos de los fármacos , Animales , Barrera Hematoencefálica/efectos de los fármacos , Humanos , Campos Magnéticos , Nanopartículas de Magnetita/efectos adversos , Nanopartículas de Magnetita/química , Ratones , Nanomedicina Teranóstica , Distribución Tisular/efectos de los fármacos

RESUMEN

Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 ( P244R/ ) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells.

Asunto(s)

Audición/fisiología , Receptores de Hialuranos/metabolismo , Células Laberínticas de Soporte/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Animales , Animales Recién Nacidos , Biomarcadores/metabolismo , Sordera/genética , Oído Interno/crecimiento & desarrollo , Perfilación de la Expresión Génica , Humanos , Receptores de Hialuranos/genética , Ratones , Ratones Noqueados , Isoformas de Proteínas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

RESUMEN

Neurons in the primary auditory cortex (AI) encode complex features of the spectral content of sound, such as direction selectivity. Recent findings of temporal symmetry in AI predict a specific organization of the subcortical input into the cortex that contributes to the emergence of direction selectivity. We demonstrate two subpopulations of neurons in the central nucleus of the inferior colliculus, which differ in their steady-state temporal response profile: lagged and non-lagged. The lagged cells (23%) are shifted in temporal phase with respect to non-lagged cells, and are characterized by an 'inhibition first' and delayed excitation in their spectro-temporal receptive fields. Non-lagged cells (77%) have a canonical 'excitation first' response. However, we find no difference in the response onset latency to pure tone stimuli between the two subpopulations. Given the homogeneity of tonal response latency, we predict that these lagged cells receive inhibitory input mediated by cortical feedback projections.

Asunto(s)

Percepción Auditiva/fisiología , Colículos Inferiores/fisiología , Neuronas/fisiología , Estimulación Acústica , Potenciales de Acción , Animales , Vías Auditivas/fisiología , Electrodos Implantados , Hurones , Microelectrodos , Inhibición Neural/fisiología , Factores de Tiempo

RESUMEN

Disrupted ontogeny of forebrain inhibitory interneurons leads to neurological disorders, including epilepsy. Adult mice lacking the urokinase plasminogen activator receptor (Plaur) have decreased numbers of neocortical GABAergic interneurons and spontaneous seizures, attributed to a reduction of hepatocyte growth factor/scatter factor (HGF/SF). We report that by increasing endogenous HGF/SF concentration in the postnatal Plaur null mouse brain maintains the interneuron populations in the adult, reverses the seizure behavior and stabilizes the spontaneous electroencephalogram activity. The perinatal intervention provides a pathway to reverse potential birth defects and ameliorate seizures in the adult.

Asunto(s)

Susceptibilidad a Enfermedades/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Interneuronas/fisiología , Inhibición Neural/fisiología , Convulsiones/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Análisis de Varianza , Animales , Animales Modificados Genéticamente , Animales Recién Nacidos , Reacción de Prevención/fisiología , Encéfalo/citología , Encéfalo/metabolismo , Electroencefalografía/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Proteína Ácida Fibrilar de la Glía/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Interneuronas/efectos de los fármacos , Ratones , Parvalbúminas/metabolismo , Pentilenotetrazol , Tiempo de Reacción/efectos de los fármacos , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Convulsiones/inducido químicamente , Convulsiones/genética , Convulsiones/patología

RESUMEN

Auditory gratings (also called auditory ripples) are a family of complex, broadband sounds with sinusoidally modulated logarithmic amplitudes and a drifting spectral envelope. These stimuli have been studied both physiologically in mammals and psychophysically in humans. Auditory gratings share spectro-temporal properties with many natural sounds, including species-specific vocalizations and the formant transitions of human speech. We successfully trained zebra finches and budgerigars, using operant conditioning methods, to discriminate between flat-spectrum broadband noise and noises with ripple spectra of different densities that moved up or down in frequency at various rates. Results show that discrimination thresholds (minimum modulation depth) increased as a function of increasing grating periodicity and density across all species. Results also show that discrimination in the two species of birds was better at those grating periodicities and densities that are prominent in their species-specific vocalizations. Budgerigars were generally more sensitive than both zebra finches and humans. Both bird species showed greater sensitivity to descending auditory gratings, which mirrors the main direction in their vocalizations. Humans, on the other hand, showed no directional preference even though speech is somewhat downward directional. Overall, our results are suggestive of both common strategies in the processing of complex sounds between birds and mammals and specialized, species-specific variations on that processing in birds.

Asunto(s)

Vías Auditivas/fisiología , Percepción Auditiva , Pinzones/fisiología , Melopsittacus/fisiología , Patrones de Reconocimiento Fisiológico , Discriminación de la Altura Tonal , Detección de Señal Psicológica , Estimulación Acústica , Animales , Umbral Auditivo , Condicionamiento Operante , Femenino , Humanos , Masculino , Psicoacústica , Espectrografía del Sonido , Especificidad de la Especie , Factores de Tiempo , Vocalización Animal

RESUMEN

This study examined the perception and cortical representation of harmonic complex tones, from the perspective of the spectral fusion evoked by such sounds. Experiment 1 tested whether ferrets spontaneously distinguish harmonic from inharmonic tones. In baseline sessions, ferrets detected a pure tone terminating a sequence of inharmonic tones. After they reached proficiency, a small fraction of the inharmonic tones were replaced with harmonic tones. Some of the animals confused the harmonic tones with the pure tones at twice the false-alarm rate. Experiment 2 sought correlates of harmonic fusion in single neurons of primary auditory cortex and anterior auditory field, by comparing responses to harmonic tones with those to inharmonic tones in the awake alert ferret. The effects of spectro-temporal filtering were accounted for by using the measured spectrotemporal receptive field to predict responses and by seeking correlates of fusion in the predictability of responses. Only 12% of units sampled distinguished harmonic tones from inharmonic tones, a small percentage that is consistent with the relatively weak ability of the ferrets to spontaneously discriminate harmonic tones from inharmonic tones in Experiment 1.

Asunto(s)

Estimulación Acústica , Corteza Auditiva/fisiología , Hurones/fisiología , Percepción , Percepción de la Altura Tonal , Animales , Percepción Auditiva , Corteza Cerebral/fisiología , Modelos Biológicos , Sonido , Vigilia

RESUMEN

Neurons in primary auditory cortex (AI) in the ferret (Mustela putorius) that are well described by their spectrotemporal response field (STRF) are found also to have a distinctive property that we call temporal symmetry. For temporally symmetric neurons, every temporal cross-section of the STRF (impulse response) is given by the same function of time, except for a scaling and a Hilbert rotation. This property held in 85% of neurons (123 out of 145) recorded from awake animals and in 96% of neurons (70 out of 73) recorded from anesthetized animals. This property of temporal symmetry is highly constraining for possible models of functional neural connectivity within and into AI. We find that the simplest models of functional thalamic input, from the ventral medial geniculate body (MGB), into the entry layers of AI are ruled out because they are incompatible with the constraints of the observed temporal symmetry. This is also the case for the simplest models of functional intracortical connectivity. Plausible models that do generate temporal symmetry, from both thalamic and intracortical inputs, are presented. In particular, we propose that two specific characteristics of the thalamocortical interface may be responsible. The first is a temporal mismatch between the fast dynamics of the thalamus and the slow responses of the cortex. The second is that all thalamic inputs into a cortical module (or a cluster of cells) must be restricted to one point of entry (or one cell in the cluster). This latter property implies a lack of correlated horizontal interactions across cortical modules during the STRF measurements. The implications of these insights in the auditory system, and comparisons with similar properties in the visual system, are explored.

Asunto(s)

Corteza Auditiva/citología , Vías Auditivas/fisiología , Red Nerviosa/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Estimulación Acústica/métodos , Animales , Corteza Auditiva/fisiología , Mapeo Encefálico , Simulación por Computador , Hurones , Modelos Neurológicos , Análisis Espectral , Visión Ocular/fisiología

RESUMEN

It is known that anesthesia depresses neural activity and inhibits cortico-cortical interactions and cortical output. Hence, it is important to record from awake animals in order to better understand the full dynamic range of neural responses. We have developed a preparation for chronic, multi-electrode physiological recording in the cortex of the awake ferret. This paper discusses several of the advantages and disadvantages of the technique as well as procedures used to overcome potential complications associated with chronic implants in the ferret. Our solutions are well suited to the special species requirements, yet are also easily generalizable to other species.

Asunto(s)

Corteza Auditiva/fisiología , Electrodos Implantados , Electrofisiología/instrumentación , Potenciales Evocados Auditivos/fisiología , Vigilia , Estimulación Acústica/métodos , Animales , Corteza Auditiva/citología , Hurones