RESUMEN
Exposure to loud noises results in neuroinflammatory responses in the central auditory pathway. Noise-induced neuroinflammation is implicated in auditory processing deficits such as impairment in gap detection. In this study, we examined whether strain differences between the FVB and C57BL/6 mice in noise-induced impairment in gap detection are correlated with strain differences in neuroinflammatory responses. We found that noise induced more robust TNF-α expression in C57BL/6 than in FVB mice. Noise-induced microglial deramification was observed in C57BL/6 mice, but not in FVB mice. Furthermore, noise exposure resulted in a reduction in parvalbumin-positive (PV+) neuron density in the C57BL/6 mice, but not in FVB mice. These results suggest that neuroinflammatory responses and loss of PV+ neurons may contribute to strain differences in noise-induced impairment in gap detection.
Asunto(s)
Trastornos de la Percepción Auditiva/genética , Ruido/efectos adversos , Parvalbúminas/metabolismo , Factor de Necrosis Tumoral alfa/genética , Animales , Trastornos de la Percepción Auditiva/etiología , Trastornos de la Percepción Auditiva/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Neuronas/metabolismo , Especificidad de la EspecieRESUMEN
Schizophrenia is a complex brain syndrome characterized by an array of positive symptoms (delusions, hallucinations, disorganized speech), negative symptoms (alogia, apathy, avolition) and cognitive impairments (memory, executive functions). Although investigations of the cognitive deficits in schizophrenia have primarily concentrated on disturbances affecting higher-order cognitive processes, there is an increasing realization that schizophrenia also affects early sensory processing, which might, in fact, play a significant role in the development of higher-order cognitive impairments. Recent evidence suggests that many of these early sensory processing impairments possibly arise from a dysregulation of plasticity regulators in schizophrenia, resulting in either reduced plasticity or excessive unregulated plasticity. The purpose of the present manuscript is to provide a concise overview of how the dysregulation of cortical plasticity mechanisms contributes to schizophrenia symptoms with an emphasis on auditory dysplasticity and to discuss its relevance for treatment outcomes. The idea that plasticity mechanisms are not constrained only within sensitive periods suggests that many functional properties of sensory neurons can be altered throughout the lifetime.
Asunto(s)
Trastornos de la Percepción Auditiva , Corteza Cerebral , Plasticidad Neuronal/fisiología , Esquizofrenia , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Percepción Auditiva/fisiopatología , Trastornos de la Percepción Auditiva/terapia , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatología , Esquizofrenia/terapiaRESUMEN
ABSTRACT Objective To compare performance in Avaliação Simplificada do Processamento Auditivo Central and Scale of Auditory Behaviors scores before and after auditory and motor training. Methods Sample comprising 162 children aged 9 to 11 years and attending public schools in the city of São Paulo (SP), Brazil; 122 out of 162 children were allocated to one of three experimental groups: Multisensory; Auditory/Motor and Motor/Auditory. Experimental groups were submitted to 8 hours of auditory, visuospatial and motor stimulation over the course of 8 weeks. The remaining 40 children formed the Control Group and received no stimulation. Results Relation between child behavior as perceived by school teachers and auditory test responses revealed that the better the performance in auditory processing assessment, the higher the Scale of Auditory Behaviors scores. Conclusion Auditory and motor training led to improvements in auditory processing skills as rated by Avaliação Simplificada do Processamento Auditivo Central and Scale of Auditory Behaviors; this intervention model proved to be a good tool for use in school settings.
RESUMO Objetivo Comparar as respostas da Avaliação Simplificada do Processamento Auditivo Central às da Scale of Auditory Behaviors antes e depois de um treinamento auditivo e de habilidades motoras. Métodos Participaram 162 escolares de 9 a 11 anos de escola pública municipal da cidade de São Paulo (SP), sendo 122 deles divididos em três grupos experimentais: Multissensorial; Auditivo/Motor e Motor/Auditivo. Eles receberam estimulação auditiva, visuoespacial e motora durante 8 semanas (8 horas). O Grupo Controle, que não recebeu estimulação, foi formado por 40 escolares. Resultados A relação entre a percepção dos professores sobre o comportamento dos alunos e suas respostas em testes auditivos mostrou que quanto melhor o resultado na avaliação do processamento auditivo, melhores os escores da Scale of Auditory Behaviors. Conclusão Após treinamento auditivo e motor, ocorreu melhora significativa das habilidades do processamento auditivo demonstradas pela Avaliação Simplificada do Processamento Auditivo Central e na Scale of Auditory Behaviors, e este modelo de intervenção consistiu em boa ferramenta para uso na escola.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Percepción Auditiva , Trastornos de la Percepción Auditiva/rehabilitación , Estimulación Acústica/métodos , Trastornos de la Percepción Auditiva/diagnóstico , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Audición/diagnósticoAsunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva , Trastornos de la Percepción Auditiva/fisiopatología , Tronco Encefálico/fisiología , Células Ciliadas Auditivas/fisiología , Trastornos de la Audición/fisiopatología , Transmisión Sináptica , Animales , Corteza Auditiva/metabolismo , Vías Auditivas/metabolismo , Vías Auditivas/fisiología , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Percepción Auditiva/psicología , Tronco Encefálico/metabolismo , Potenciales Evocados Auditivos del Tronco Encefálico , Células Ciliadas Auditivas/metabolismo , Trastornos de la Audición/metabolismo , Trastornos de la Audición/psicología , Humanos , Proteínas del Tejido Nervioso/metabolismoRESUMEN
The auxiliary subunit α2δ3 modulates the expression and function of voltage-gated calcium channels. Here we show that α2δ3 mRNA is expressed in spiral ganglion neurons and auditory brainstem nuclei and that the protein is required for normal acoustic responses. Genetic deletion of α2δ3 led to impaired auditory processing, with reduced acoustic startle and distorted auditory brainstem responses. α2δ3(-/-) mice learned to discriminate pure tones, but they failed to discriminate temporally structured amplitude-modulated tones. Light and electron microscopy analyses revealed reduced levels of presynaptic Ca(2+) channels and smaller auditory nerve fiber terminals contacting cochlear nucleus bushy cells. Juxtacellular in vivo recordings of sound-evoked activity in α2δ3(-/-) mice demonstrated impaired transmission at these synapses. Together, our results identify a novel role for the α2δ3 auxiliary subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.
Asunto(s)
Trastornos de la Percepción Auditiva/metabolismo , Canales de Calcio/metabolismo , Nervio Coclear/metabolismo , Aprendizaje Discriminativo/fisiología , Sinapsis/metabolismo , Animales , Trastornos de la Percepción Auditiva/genética , Trastornos de la Percepción Auditiva/fisiopatología , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Canales de Calcio/genética , Nervio Coclear/patología , Electrofisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Inmunohistoquímica , Hibridación in Situ , Ratones , Ratones Noqueados , Microscopía Electrónica de Transmisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ganglio Espiral de la Cóclea/metabolismo , Ganglio Espiral de la Cóclea/fisiología , Sinapsis/patología , Transmisión Sináptica/fisiologíaRESUMEN
This article reviews and synthesizes recent research regarding auditory processing, attention, and their roles in generating both adaptive and maladaptive behavioral responses. Research in these areas is beginning to converge on the role of polymorphisms associated with catecholamine metabolism and transport, particularly the neurotransmitter dopamine. The synthesis offered in this article appears to be the first to argue that genetic differences in dopamine metabolism may be the common factor in four disparate disorders that are often observed to be comorbid, i.e., attention-deficit hyperactivity disorder, auditory processing disorders, developmental language disorders, and reading disorders.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Atención/fisiología , Percepción Auditiva/fisiología , Trastornos de la Percepción Auditiva , Dislexia , Trastornos del Desarrollo del Lenguaje , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastornos de la Percepción Auditiva/genética , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Percepción Auditiva/fisiopatología , Dislexia/genética , Dislexia/metabolismo , Dislexia/fisiopatología , Humanos , Trastornos del Desarrollo del Lenguaje/genética , Trastornos del Desarrollo del Lenguaje/metabolismo , Trastornos del Desarrollo del Lenguaje/fisiopatologíaRESUMEN
Heterozygous mutations of the human FOXP2 gene are implicated in a severe speech and language disorder. Aetiological mutations of murine Foxp2 yield abnormal synaptic plasticity and impaired motor-skill learning in mutant mice, while knockdown of the avian orthologue in songbirds interferes with auditory-guided vocal learning. Here, we investigate influences of two distinct Foxp2 point mutations on vocalizations of 4-day-old mouse pups (Mus musculus). The R552H missense mutation is identical to that causing speech and language deficits in a large well-studied human family, while the S321X nonsense mutation represents a null allele that does not produce Foxp2 protein. We ask whether vocalizations, based solely on innate mechanisms of production, are affected by these alternative Foxp2 mutations. Sound recordings were taken in two different situations: isolation and distress, eliciting a range of call types, including broadband vocalizations of varying noise content, ultrasonic whistles and clicks. Sound production rates and several acoustic parameters showed that, despite absence of functional Foxp2, homozygous mutants could vocalize all types of sounds in a normal temporal pattern, but only at comparably low intensities. We suggest that altered vocal output of these homozygotes may be secondary to developmental delays and somatic weakness. Heterozygous mutants did not differ from wild-types in any of the measures that we studied (R552H ) or in only a few (S321X ), which were in the range of differences routinely observed for different mouse strains. Thus, Foxp2 is not essential for the innate production of emotional vocalizations with largely normal acoustic properties by mouse pups.
Asunto(s)
Envejecimiento/genética , Factores de Transcripción Forkhead/deficiencia , Factores de Transcripción Forkhead/genética , Proteínas Represoras/deficiencia , Proteínas Represoras/genética , Vocalización Animal/fisiología , Estimulación Acústica , Envejecimiento/fisiología , Animales , Trastornos de la Percepción Auditiva/genética , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Percepción Auditiva/patología , Codón sin Sentido/genética , Femenino , Factores de Transcripción Forkhead/fisiología , Regulación del Desarrollo de la Expresión Génica , Tamización de Portadores Genéticos , Humanos , Masculino , Ratones , Ratones Mutantes , Mutación Missense/genética , Plasticidad Neuronal/genética , Proteínas Represoras/fisiologíaRESUMEN
Mechanosensory hair cells of the organ of Corti transmit information regarding sound to the central nervous system by way of peripheral afferent neurons. In return, the central nervous system provides feedback and modulates the afferent stream of information through efferent neurons. The medial olivocochlear efferent system makes direct synaptic contacts with outer hair cells and inhibits amplification brought about by the active mechanical process inherent to these cells. This feedback system offers the potential to improve the detection of signals in background noise, to selectively attend to particular signals, and to protect the periphery from damage caused by overly loud sounds. Acetylcholine released at the synapse between efferent terminals and outer hair cells activates a peculiar nicotinic cholinergic receptor subtype, the alpha9alpha10 receptor. At present no pharmacotherapeutic approaches have been designed that target this cholinergic receptor to treat pathologies of the auditory system. The potential use of alpha9alpha10 selective drugs in conditions such as noise-induced hearing loss, tinnitus and auditory processing disorders is discussed.
Asunto(s)
Células Ciliadas Auditivas/fisiología , Receptores Nicotínicos/fisiología , Acetilcolina/metabolismo , Animales , Trastornos de la Percepción Auditiva/tratamiento farmacológico , Trastornos de la Percepción Auditiva/metabolismo , Cóclea/anatomía & histología , Cóclea/fisiología , Dislexia/tratamiento farmacológico , Dislexia/metabolismo , Pérdida Auditiva/tratamiento farmacológico , Pérdida Auditiva/etiología , Humanos , Ruido/efectos adversos , Núcleo Olivar/fisiología , Subunidades de Proteína/fisiología , Transmisión Sináptica , Acúfeno/tratamiento farmacológico , Acúfeno/metabolismoRESUMEN
Abnormal auditory gating is a symptom of schizophrenia which has been proposed to be mediated through the alpha7 nicotinic acetylcholine receptor (nAChR). It has been shown that the non-selective nicotinic agonist nicotine has an influence on auditory gating in part by acting on the alpha4beta2 nAChR. The goal of this study was to determine the effect of 5-I A-85380, an agonist for the alpha4beta2 nAChR, in an inbred mouse model with a deficiency for auditory gating. Anesthetized DBA/2 mice were administered 5-I A-85380 alone and in combination with the alpha4beta2 nAChR antagonist, dihydro-beta-erythroidine, or the alpha7 nAChR antagonist, alpha-bungarotoxin. A recording electrode in the CA3 region of the hippocampus recorded P20-N40 waveforms in response to two auditory stimuli. The amplitudes of the response to the first and second clicks were used to determine TC ratios, the measure of auditory gating. 5-I A-85380 significantly decreased the TC ratios by selectively increasing the response amplitudes to the first click with no significant influence on the response amplitudes to the second click. The effect was blocked by dihydro-beta-erythroidine whereas alpha-bungarotoxin had no effect on response amplitude to either click. Although the alpha7 nAChR may mediate the hippocampal response of DBA/2 mice to the second click, the alpha4beta2 nAChR appears to modulate the response to the first click. Thus, the present study implicates the involvement of more than one subtype of nAChR in the auditory gating of DBA/2 mice, specifically the alpha4beta2 nAChR, and its role in the response amplitude to the first stimulus.
Asunto(s)
Trastornos de la Percepción Auditiva/tratamiento farmacológico , Azetidinas/farmacología , Hipocampo/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Agonistas Nicotínicos/farmacología , Piridinas/farmacología , Receptores Nicotínicos/efectos de los fármacos , Acetilcolina/metabolismo , Estimulación Acústica , Animales , Percepción Auditiva/efectos de los fármacos , Percepción Auditiva/fisiología , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Percepción Auditiva/fisiopatología , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Ratones , Ratones Endogámicos DBA , Inhibición Neural/fisiología , Antagonistas Nicotínicos/farmacología , Receptores Nicotínicos/metabolismo , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatología , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Receptor Nicotínico de Acetilcolina alfa 7RESUMEN
Congenital deafness is a severe, incurable and hardly correctable inherited disease. Mutations in GCB2 and GJB6 genes are most prevalent causes of deafness and occur in patients with hereditary and sporadic deafness all over the world. Some ethnic groups exhibit high rate of heterozygous carriage of most frequent GJB2 mutations (35delG, 167delT, 235delC). Definite association of hereditary deafness and mutational alterations in genes of connexins 26, 30 and 31 shows high informative value of molecular-genetic methods which diagnose hereditary deafness, carriage of mutations in GJB2, GJB3 and GJB6 genes, provide definite probability of the disease in medico-genetic consulting. Further progress in genetics of hereditary hearing loss will raise efficacy of deafness diagnosis at early stages of fetal development and prevent birth of babies with congenital defects of sound perception.
Asunto(s)
Trastornos de la Percepción Auditiva/genética , Trastornos de la Percepción Auditiva/metabolismo , Conexinas/genética , Trastornos de la Percepción Auditiva/etnología , Conexina 26 , Conexina 30 , Etnicidad/estadística & datos numéricos , Células Ciliadas Auditivas Externas/metabolismo , Humanos , Mutación Puntual/genética , Polimorfismo Genético/genéticaRESUMEN
We investigated whether a 2-month dietary supplementation of antioxidants, in the form of blueberry phytochemicals, could reverse or retard the age-related decline in temporal processing speed observed in the aged rat. To this end, extracellular single unit responses to frequency modulated (FM) sweeps were recorded in the primary auditory cortex (AI) of aged rats that had been placed on either a blueberry-supplemented or control diet 2 months prior to the physiological recordings. Results showed that most cells recorded from the blueberry-fed rats responded most vigorously to fast FM sweeps, similar to that observed in young rats. In contrast, the majority of cells recorded from the control rats showed a preference for slow FM sweep rates. These results suggest that age-related changes in temporal processing speed in A1 may be reversed by dietary supplementation of blueberry phytochemicals.
Asunto(s)
Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Antioxidantes/farmacología , Corteza Auditiva/efectos de los fármacos , Corteza Auditiva/metabolismo , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Antioxidantes/uso terapéutico , Percepción Auditiva/efectos de los fármacos , Percepción Auditiva/fisiología , Trastornos de la Percepción Auditiva/tratamiento farmacológico , Trastornos de la Percepción Auditiva/metabolismo , Trastornos de la Percepción Auditiva/prevención & control , Arándanos Azules (Planta)/química , Potenciales Evocados Auditivos/efectos de los fármacos , Potenciales Evocados Auditivos/fisiología , Alimentos Formulados , Masculino , Neuronas/efectos de los fármacos , Neuronas/fisiología , Ratas , Ratas Long-Evans , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiologíaRESUMEN
The dopamine (DA) system has long been associated with the pathophysiology of psychosis. The DA theory of schizophrenia continues to find support in neuroreceptor imaging and ligand-binding studies that show excess DA transmission in patients, as compared to controls. The pathways that regulate the primate DA system, however, have yet to be fully elucidated. The amygdala, including its extended amygdala component, is involved in evaluating the emotional value of sensory stimuli. Since emotionally relevant sensory stimuli are distorted during psychotic episodes, we hypothesize that amygdaloid influences are likely to be significant modulators of the DA system. We reviewed evidence for direct projections from the central extended amygdala to specific subpopulations of DA neurons, and we discuss how these pathways may serve as important conduits of emotionally relevant information that can have immediate and long-term effects on DA regulation.
Asunto(s)
Amígdala del Cerebelo/fisiología , Dopamina/fisiología , Amígdala del Cerebelo/anatomía & histología , Animales , Trastornos de la Percepción Auditiva/metabolismo , Humanos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Neuronas/metabolismo , Sustancia Negra/anatomía & histología , Sustancia Negra/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Normal sensory transduction requires the efficient disposal of acid (H+) generated by neuronal and sensory receptor activity. Multiple highly sensitive transport mechanisms have evolved in prokaryotic and eukaryotic organisms to maintain acidity within strict limits. It is currently assumed that the multiplicity of these processes provides a biological robustness. Here we report that the visual and auditory systems have a specific requirement for H+ disposal mediated by the sodium bicarbonate cotransporter NBC3 (refs. 7,8). Mice lacking NBC3 develop blindness and auditory impairment because of degeneration of sensory receptors in the eye and inner ear as in Usher syndrome. Our results indicate that in certain sensory organs, in which the requirement to transduce specific environmental signals with speed, sensitivity and reliability is paramount, the choice of the H+ disposal mechanism used is limited.
Asunto(s)
Trastornos de la Percepción Auditiva/etiología , Ceguera/etiología , Simportadores de Sodio-Bicarbonato/deficiencia , Animales , Apoptosis , Trastornos de la Percepción Auditiva/metabolismo , Ceguera/metabolismo , Electrorretinografía , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Angiografía con Fluoresceína , Marcación de Gen , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Endogámicos C57BL , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patología , Degeneración Retiniana/etiología , Degeneración Retiniana/metabolismo , Degeneración Retiniana/patología , Simportadores de Sodio-Bicarbonato/fisiologíaAsunto(s)
Trastornos de la Percepción Auditiva/fisiopatología , Dopamina/fisiología , Alucinaciones/fisiopatología , Esquizofrenia/fisiopatología , Corteza Auditiva/metabolismo , Trastornos de la Percepción Auditiva/metabolismo , Dopamina/metabolismo , Alucinaciones/metabolismo , Humanos , Esquizofrenia/metabolismo , Psicología del EsquizofrénicoRESUMEN
OBJECTIVE: This study asks whether auditory hallucinations are reflected in a distinctive metabolic map of the brain. METHOD: Regional brain metabolism was measured by positron emission tomography with [18F]-fluorodeoxyglucose in 12 DSM-III schizophrenic patients who experienced auditory hallucinations during glucose uptake and 10 who did not. All patients were free of neuroleptics and 19 had never been treated with neuroleptics. Nine patients were reexamined after 1 year to assess effects of neuroleptic treatment. RESULTS: Compared with the patients who did not experience hallucinations, the patients who did experience hallucinations had significantly lower relative metabolism in auditory and Wernicke's regions and a trend toward higher metabolism in the right hemisphere homologue of Broca's region. Hallucination scores correlated positively and significantly with relative metabolism in the striatum and anterior cingulate regions. Neuroleptic treatment resulted in a significant increase in striatal metabolism and a reduced frontal-parietal ratio, which was significantly correlated with a decrease in hallucination scores. CONCLUSIONS: Auditory hallucinations involve language regions of the cortex in a pattern similar to that seen in normal subjects listening to their own voices but different in that left prefrontal regions are not activated. The striatum plays a critical role in auditory hallucinations.