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[PMID]:29287884
[Au] Autor:Kim BJ; Kim J; Park IY; Jung JY; Suh MW; Oh SH
[Ad] Endereço:Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul, South Korea.
[Ti] Título:Effects of transient auditory deprivation during critical periods on the development of auditory temporal processing.
[So] Source:Int J Pediatr Otorhinolaryngol;104:66-71, 2018 Jan.
[Is] ISSN:1872-8464
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The central auditory pathway matures through sensory experiences and it is known that sensory experiences during periods called critical periods exert an important influence on brain development. The present study aimed to investigate whether temporary auditory deprivation during critical periods (CPs) could have a detrimental effect on the development of auditory temporal processing. MATERIALS AND METHODS: Twelve neonatal rats were randomly assigned to control and study groups; Study group experienced temporary (18-20 days) auditory deprivation during CPs (Early deprivation study group). Outcome measures included changes in auditory brainstem response (ABR), gap prepulse inhibition of the acoustic startle reflex (GPIAS), and gap detection threshold (GDT). To further delineate the specific role of CPs in the outcome measures above, the same paradigm was applied in adult rats (Late deprivation group) and the findings were compared with those of the neonatal rats. RESULTS: Soon after the restoration of hearing, early deprivation study animals showed a significantly lower GPIAS at intermediate gap durations and a larger GDT than early deprivation controls, but these differences became insignificant after subsequent auditory inputs. Additionally, the ABR results showed significantly delayed latencies of waves IV, V, and interpeak latencies of wave I-III and wave I-V in study group. Late deprivation group didn't exhibit any deterioration in temporal processing following sensory deprivation. CONCLUSION: Taken together, the present results suggest that transient auditory deprivation during CPs might cause reversible disruptions in the development of temporal processing.
[Mh] Termos MeSH primário: Vias Auditivas/fisiologia
Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia
Reflexo de Sobressalto/fisiologia
Privação Sensorial/fisiologia
[Mh] Termos MeSH secundário: Animais
Limiar Auditivo
Período Crítico (Psicologia)
Testes Auditivos
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  2 / 7448 MEDLINE  
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[PMID]:28469562
[Au] Autor:Di Bonito M; Studer M
[Ad] Endereço:Université Côte d'Azur, CNRS, Inserm, iBVNice, France.
[Ti] Título:Cellular and Molecular Underpinnings of Neuronal Assembly in the Central Auditory System during Mouse Development.
[So] Source:Front Neural Circuits;11:18, 2017.
[Is] ISSN:1662-5110
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:During development, the organization of the auditory system into distinct functional subcircuits depends on the spatially and temporally ordered sequence of neuronal specification, differentiation, migration and connectivity. Regional patterning along the antero-posterior axis and neuronal subtype specification along the dorso-ventral axis intersect to determine proper neuronal fate and assembly of rhombomere-specific auditory subcircuits. By taking advantage of the increasing number of transgenic mouse lines, recent studies have expanded the knowledge of developmental mechanisms involved in the formation and refinement of the auditory system. Here, we summarize several findings dealing with the molecular and cellular mechanisms that underlie the assembly of central auditory subcircuits during mouse development, focusing primarily on the rhombomeric and dorso-ventral origin of auditory nuclei and their associated molecular genetic pathways.
[Mh] Termos MeSH primário: Vias Auditivas
Regulação da Expressão Gênica no Desenvolvimento/fisiologia
Neurônios/fisiologia
[Mh] Termos MeSH secundário: Animais
Vias Auditivas/citologia
Vias Auditivas/embriologia
Vias Auditivas/crescimento & desenvolvimento
Diferenciação Celular
Movimento Celular
Camundongos
Neurônios/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.3389/fncir.2017.00018


  3 / 7448 MEDLINE  
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[PMID]:28450830
[Au] Autor:Elliott KL; Kersigo J; Pan N; Jahan I; Fritzsch B
[Ad] Endereço:Department of Biology, University of IowaIowa City, IA, USA.
[Ti] Título:Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking Peripheral and/or Central Target Differentiation.
[So] Source:Front Neural Circuits;11:25, 2017.
[Is] ISSN:1662-5110
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:We investigate the importance of the degree of peripheral or central target differentiation for mouse auditory afferent navigation to the organ of Corti and auditory nuclei in three different mouse models: first, a mouse in which the differentiation of hair cells, but not central auditory nuclei neurons is compromised ( ); second, a mouse in which hair cell defects are combined with a delayed defect in central auditory nuclei neurons ( ), and third, a mouse in which both hair cells and central auditory nuclei are absent ( ). Our results show that neither differentiated peripheral nor the central target cells of inner ear afferents are needed (hair cells, cochlear nucleus neurons) for segregation of vestibular and cochlear afferents within the hindbrain and some degree of base to apex segregation of cochlear afferents. These data suggest that inner ear spiral ganglion neuron processes may predominantly rely on temporally and spatially distinct molecular cues in the region of the targets rather than interaction with differentiated target cells for a crude topological organization. These developmental data imply that auditory neuron navigation properties may have evolved before auditory nuclei.
[Mh] Termos MeSH primário: Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência
Diferenciação Celular/genética
Células Ciliadas Auditivas/fisiologia
Malformações do Sistema Nervoso/patologia
Fator de Transcrição PAX2/deficiência
Rombencéfalo/patologia
Gânglio Espiral da Cóclea
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Vias Auditivas/embriologia
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Núcleo Coclear/citologia
Núcleo Coclear/embriologia
Núcleo Coclear/crescimento & desenvolvimento
Embrião de Mamíferos
Camundongos
Camundongos Knockout
Malformações do Sistema Nervoso/genética
Fator de Transcrição PAX2/genética
Gânglio Espiral da Cóclea/embriologia
Gânglio Espiral da Cóclea/crescimento & desenvolvimento
Gânglio Espiral da Cóclea/patologia
beta-Galactosidase/genética
beta-Galactosidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Atoh1 protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (PAX2 Transcription Factor); 0 (Pax2 protein, mouse); EC 3.2.1.23 (beta-Galactosidase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.3389/fncir.2017.00025


  4 / 7448 MEDLINE  
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[PMID]:27770624
[Au] Autor:Rocchi F; Dylla ME; Bohlen PA; Ramachandran R
[Ad] Endereço:Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
[Ti] Título:Spatial and temporal disparity in signals and maskers affects signal detection in non-human primates.
[So] Source:Hear Res;344:1-12, 2017 Feb.
[Is] ISSN:1878-5891
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Detection thresholds for auditory stimuli (signals) increase in the presence of maskers. Natural environments contain maskers/distractors that can have a wide range of spatiotemporal properties relative to the signal. While these parameters have been well explored psychophysically in humans, they have not been well explored in animal models, and their neuronal underpinnings are not well understood. As a precursor to the neuronal measurements, we report the effects of systematically varying the spatial and temporal relationship between signals and noise in macaque monkeys (Macaca mulatta and Macaca radiata). Macaques detected tones masked by noise in a Go/No-Go task in which the spatiotemporal relationships between the tone and noise were systematically varied. Masked thresholds were higher when the masker was continuous or gated on and off simultaneously with the signal, and lower when the continuous masker was turned off during the signal. A burst of noise caused higher masked thresholds if it completely temporally overlapped with the signal, whereas partial overlap resulted in lower thresholds. Noise durations needed to be at least 100 ms before significant masking could be observed. Thresholds for short duration tones were significantly higher when the onsets of signal and masker coincided compared to when the signal was presented during the steady state portion of the noise (overshoot). When signal and masker were separated in space, masked signal detection thresholds decreased relative to when the masker and signal were co-located (spatial release from masking). Masking release was larger for azimuthal separations than for elevation separations. These results in macaques are similar to those observed in humans, suggesting that the specific spatiotemporal relationship between signal and masker determine threshold in natural environments for macaques in a manner similar to humans. These results form the basis for future investigations of neuronal correlates and mechanisms of masking.
[Mh] Termos MeSH primário: Comportamento Animal
Sinais (Psicologia)
Ruído/efeitos adversos
Mascaramento Perceptivo
Nível de Percepção Sonora
Detecção de Sinal Psicológico
Localização de Som
[Mh] Termos MeSH secundário: Estimulação Acústica
Animais
Audiometria
Vias Auditivas/fisiologia
Limiar Auditivo
Macaca mulatta
Macaca radiata
Masculino
Modelos Animais
Periodicidade
Psicoacústica
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


  5 / 7448 MEDLINE  
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[PMID]:28947575
[Au] Autor:Goldwyn JH; McLaughlin M; Verschooten E; Joris PX; Rinzel J
[Ad] Endereço:Department of Mathematics, Ohio State University, Columbus, Ohio 43210, jhgoldwyn@gmail.com.
[Ti] Título:Signatures of Somatic Inhibition and Dendritic Excitation in Auditory Brainstem Field Potentials.
[So] Source:J Neurosci;37(43):10451-10467, 2017 Oct 25.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extracellular voltage recordings ( ; field potentials) provide an accessible view of neural activity, but proper interpretation of field potentials is a long-standing challenge. Computational modeling can aid in identifying neural generators of field potentials. In the auditory brainstem of cats, spatial patterns of sound-evoked can resemble, strikingly, generated by current dipoles. Previously, we developed a biophysically-based model of a binaural brainstem nucleus, the medial superior olive (MSO), that accounts qualitatively for observed dipole-like patterns in sustained responses to monaural tones with frequencies >∼1000 Hz (Goldwyn et al., 2014). We have observed, however, that patterns in cats of both sexes appear more monopole-like for lower-frequency tones. Here, we enhance our theory to accurately reproduce dipole and non-dipole features of responses to monaural tones with frequencies ranging from 600 to 1800 Hz. By applying our model to data, we estimate time courses of paired input currents to MSO neurons. We interpret these inputs as dendrite-targeting excitation and soma-targeting inhibition (the latter contributes non-dipole-like features to responses). Aspects of inferred inputs are consistent with synaptic inputs to MSO neurons including the tendencies of inhibitory inputs to attenuate in response to high-frequency tones and to precede excitatory inputs. Importantly, our updated theory can be tested experimentally by blocking synaptic inputs. MSO neurons perform a critical role in sound localization and binaural hearing. By solving an inverse problem to uncover synaptic inputs from patterns we provide a new perspective on MSO physiology. Extracellular voltages (field potentials) are a common measure of brain activity. Ideally, one could infer from these data the activity of neurons and synapses that generate field potentials, but this "inverse problem" is not easily solved. We study brainstem field potentials in the region of the medial superior olive (MSO); a critical center in the auditory pathway. These field potentials exhibit distinctive spatial and temporal patterns in response to pure tone sounds. We use mathematical modeling in combination with physiological and anatomical knowledge of MSO neurons to plausibly explain how dendrite-targeting excitation and soma-targeting inhibition generate these field potentials. Inferring putative synaptic currents from field potentials advances our ability to study neural processing of sound in the MSO.
[Mh] Termos MeSH primário: Estimulação Acústica/métodos
Vias Auditivas/fisiologia
Tronco Encefálico/fisiologia
Dendritos/fisiologia
Potenciais Evocados Auditivos/fisiologia
Inibição Neural/fisiologia
[Mh] Termos MeSH secundário: Animais
Vias Auditivas/citologia
Tronco Encefálico/citologia
Gatos
Feminino
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0600-17.2017


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[PMID]:28866362
[Au] Autor:Fritzsch B; Elliott KL
[Ad] Endereço:University of Iowa, Department of Biology, Iowa City, IA 52242, United States. Electronic address: bernd-fritzsch@uiowa.edu.
[Ti] Título:Gene, cell, and organ multiplication drives inner ear evolution.
[So] Source:Dev Biol;431(1):3-15, 2017 11 01.
[Is] ISSN:1095-564X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We review the development and evolution of the ear neurosensory cells, the aggregation of neurosensory cells into an otic placode, the evolution of novel neurosensory structures dedicated to hearing and the evolution of novel nuclei in the brain and their input dedicated to processing those novel auditory stimuli. The evolution of the apparently novel auditory system lies in duplication and diversification of cell fate transcription regulation that allows variation at the cellular level [transforming a single neurosensory cell into a sensory cell connected to its targets by a sensory neuron as well as diversifying hair cells], organ level [duplication of organ development followed by diversification and novel stimulus acquisition] and brain nuclear level [multiplication of transcription factors to regulate various neuron and neuron aggregate fate to transform the spinal cord into the unique hindbrain organization]. Tying cell fate changes driven by bHLH and other transcription factors into cell and organ changes is at the moment tentative as not all relevant factors are known and their gene regulatory network is only rudimentary understood. Future research can use the blueprint proposed here to provide both the deeper molecular evolutionary understanding as well as a more detailed appreciation of developmental networks. This understanding can reveal how an auditory system evolved through transformation of existing cell fate determining networks and thus how neurosensory evolution occurred through molecular changes affecting cell fate decision processes. Appreciating the evolutionary cascade of developmental program changes could allow identifying essential steps needed to restore cells and organs in the future.
[Mh] Termos MeSH primário: Evolução Biológica
Orelha Interna/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Animais
Vias Auditivas/crescimento & desenvolvimento
Vias Auditivas/fisiologia
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia
Orelha Interna/anatomia & histologia
Orelha Interna/fisiologia
Evolução Molecular
Duplicação Gênica
Células Ciliadas Auditivas/citologia
Células Ciliadas Auditivas/fisiologia
Audição/genética
Audição/fisiologia
Mecanorreceptores/citologia
Mecanorreceptores/fisiologia
Modelos Biológicos
Células Receptoras Sensoriais/citologia
Células Receptoras Sensoriais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170904
[St] Status:MEDLINE


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[PMID]:28863144
[Au] Autor:Peng K; Peng YJ; Wang J; Yang MJ; Fu ZY; Tang J; Chen QC
[Ad] Endereço:School of Life Sciences and Hubei Key Lab of Genetic Regulation & Integrative Biology, Central China Normal University, Wuhan, China.
[Ti] Título:Latency modulation of collicular neurons induced by electric stimulation of the auditory cortex in Hipposideros pratti: In vivo intracellular recording.
[So] Source:PLoS One;12(9):e0184097, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the auditory pathway, the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from the lower auditory nuclei, contralateral IC, and auditory cortex (AC), and then uploads these inputs to the thalamus and cortex. Meanwhile, the AC modulates the sound signal processing of IC neurons, including their latency (i.e., first-spike latency). Excitatory and inhibitory corticofugal projections to the IC may shorten and prolong the latency of IC neurons, respectively. However, the synaptic mechanisms underlying the corticofugal latency modulation of IC neurons remain unclear. Thus, this study probed these mechanisms via in vivo intracellular recording and acoustic and focal electric stimulation. The AC latency modulation of IC neurons is possibly mediated by pre-spike depolarization duration, pre-spike hyperpolarization duration, and spike onset time. This study suggests an effective strategy for the timing sequence determination of auditory information uploaded to the thalamus and cortex.
[Mh] Termos MeSH primário: Córtex Auditivo/fisiologia
Vias Auditivas/fisiologia
Quirópteros/fisiologia
Estimulação Elétrica
Colículos Inferiores/fisiologia
Neurônios/fisiologia
[Mh] Termos MeSH secundário: Estimulação Acústica
Acústica
Animais
Percepção Auditiva/fisiologia
Peso Corporal
Córtex Cerebral/fisiologia
Ecolocação
Feminino
Masculino
Som
Tálamo/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184097


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[PMID]:28823727
[Au] Autor:Kim WB; Cho JH
[Ad] Endereço:Department of Molecular, Cell, and Systems Biology, University of California, Riverside, Riverside, CA 92521, USA.
[Ti] Título:Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.
[So] Source:Neuron;95(5):1129-1146.e5, 2017 Aug 30.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT.
[Mh] Termos MeSH primário: Tonsila do Cerebelo/fisiologia
Discriminação (Psicologia)/fisiologia
Medo/fisiologia
Potenciação de Longa Duração/fisiologia
Memória/fisiologia
[Mh] Termos MeSH secundário: Estimulação Acústica
Animais
Vias Auditivas/fisiologia
Condicionamento (Psicologia)/fisiologia
Estimulação Elétrica
Extinção Psicológica/fisiologia
Feminino
Depressão Sináptica de Longo Prazo/fisiologia
Masculino
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE


  9 / 7448 MEDLINE  
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[PMID]:28760859
[Au] Autor:Sinclair JL; Fischl MJ; Alexandrova O; Heß M; Grothe B; Leibold C; Kopp-Scheinpflug C
[Ad] Endereço:Division of Neurobiology, Department Biology II, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany.
[Ti] Título:Sound-Evoked Activity Influences Myelination of Brainstem Axons in the Trapezoid Body.
[So] Source:J Neurosci;37(34):8239-8255, 2017 Aug 23.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Plasticity of myelination represents a mechanism to tune the flow of information by balancing functional requirements with metabolic and spatial constraints. The auditory system is heavily myelinated and operates at the upper limits of action potential generation frequency and speed observed in the mammalian CNS. This study aimed to characterize the development of myelin within the trapezoid body, a central auditory fiber tract, and determine the influence sensory experience has on this process in mice of both sexes. We find that conduction speed doubles following hearing onset and the ability to support high-frequency firing increases concurrently. Also in this time, the diameter of trapezoid body axons and the thickness of myelin double, reaching mature-like thickness between 25 and 35 d of age. Earplugs were used to induce ∼50 dB elevation in auditory thresholds. If introduced at hearing onset, trapezoid body fibers developed thinner axons and myelin than age-matched controls. If plugged during adulthood, the thickest trapezoid body fibers also showed a decrease in myelin. These data demonstrate the need for sensory activity in both development and maintenance of myelin and have important implications in the study of myelin plasticity and how this could relate to sensorineural hearing loss following peripheral impairment. The auditory system has many mechanisms to maximize the dynamic range of its afferent fibers, which operate at the physiological limit of action potential generation, precision, and speed. In this study we demonstrate for the first time that changes in peripheral activity modifies the thickness of myelin in sensory neurons, not only in development but also in mature animals. The current study suggests that changes in CNS myelination occur as a downstream mechanism following peripheral deficit. Given the required submillisecond temporal precision for binaural auditory processing, reduced myelination might augment sensorineural hearing impairment.
[Mh] Termos MeSH primário: Estimulação Acústica/métodos
Vias Auditivas/fisiologia
Axônios/fisiologia
Potenciais Evocados Auditivos/fisiologia
Fibras Nervosas Mielinizadas/fisiologia
Corpo Trapezoide/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Animais
Vias Auditivas/citologia
Tronco Encefálico/citologia
Tronco Encefálico/fisiologia
Feminino
Masculino
Camundongos
Camundongos Endogâmicos CBA
Técnicas de Cultura de Órgãos
Som
Corpo Trapezoide/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3728-16.2017


  10 / 7448 MEDLINE  
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[PMID]:28674175
[Au] Autor:Garcia-Pino E; Gessele N; Koch U
[Ad] Endereço:Institute of Biology, Neurophysiology, Freie Universität Berlin, 14195 Berlin, Germany, and.
[Ti] Título:Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.
[So] Source:J Neurosci;37(31):7403-7419, 2017 Aug 02.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social interactions, contributing to their isolation. Here, a mouse model of FXS was used to investigate the auditory brainstem where basic sound information is first processed. Loss of the Fragile X mental retardation protein leads to excessive excitatory compared with inhibitory inputs in neurons extracting information about sound levels. Functionally, this elevated excitation results in increased firing rates, and abnormal coding of frequency and binaural sound localization cues. Imbalanced early-stage sound level processing could partially explain the auditory processing deficits in FXS.
[Mh] Termos MeSH primário: Vias Auditivas/fisiopatologia
Percepção Auditiva
Tronco Encefálico/fisiopatologia
Potenciais Evocados Auditivos do Tronco Encefálico
Síndrome do Cromossomo X Frágil/fisiopatologia
Transtornos da Audição/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Córtex Auditivo/fisiopatologia
Potenciais Pós-Sinápticos Excitadores
Feminino
Proteína do X Frágil de Retardo Mental/genética
Masculino
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fmr1 protein, mouse); 139135-51-6 (Fragile X Mental Retardation Protein)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2310-16.2017



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