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J Neurosci ; 38(19): 4598-4609, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29661967


In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB.SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell-cell adhesion between chain-forming neuroblasts, which involves adherens junction-like structures. Our results suggest that Fyn-mediated regulation of the cell-cell adhesion of neuroblasts is critical for their detachment from chains in the postnatal brain.

J Neurosci ; 37(25): 6149-6161, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28559384


Feedback signals from the primary auditory cortex (A1) can shape the receptive field properties of neurons in the ventral division of the medial geniculate body (MGBv). However, the behavioral significance of corticothalamic modulation is unknown. The aim of this study was to elucidate the role of this descending pathway in the perception of complex sounds. We tested the ability of adult female ferrets to detect the presence of a mistuned harmonic in a complex tone using a positive conditioned go/no-go behavioral paradigm before and after the input from layer VI in A1 to MGBv was bilaterally and selectively eliminated using chromophore-targeted laser photolysis. MGBv neurons were identified by their short latencies and sharp tuning curves. They responded robustly to harmonic complex tones and exhibited an increase in firing rate and temporal pattern changes when one frequency component in the complex tone was mistuned. Injections of fluorescent microbeads conjugated with a light-sensitive chromophore were made in MGBv, and, following retrograde transport to the cortical cell bodies, apoptosis was induced by infrared laser illumination of A1. This resulted in a selective loss of ∼60% of layer VI A1-MGBv neurons. After the lesion, mistuning detection was impaired, as indicated by decreased d' values, a shift of the psychometric curves toward higher mistuning values, and increased thresholds, whereas discrimination performance was unaffected when level cues were also available. Our results suggest that A1-MGBv corticothalamic feedback contributes to the detection of harmonicity, one of the most important grouping cues in the perception of complex sounds.SIGNIFICANCE STATEMENT Perception of a complex auditory scene is based on the ability of the brain to group those sound components that belong to the same source and to segregate them from those belonging to different sources. Because two people talking simultaneously may differ in their voice pitch, perceiving the harmonic structure of sounds is very important for auditory scene analysis. Here we demonstrate mistuning sensitivity in the thalamus and that feedback from the primary auditory cortex is required for the normal ability of ferrets to detect a mistuned harmonic within a complex sound. These results provide novel insight into the function of descending sensory pathways in the brain and suggest that this corticothalamic circuit plays an important role in scene analysis.

Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Retroalimentação Fisiológica/fisiologia , Furões/fisiologia , Tálamo/fisiologia , Estimulação Acústica , Animais , Córtex Auditivo/citologia , Córtex Auditivo/diagnóstico por imagem , Limiar Auditivo/fisiologia , Comportamento Animal/fisiologia , Sinais (Psicologia) , Discriminação (Psicologia)/fisiologia , Feminino , Corpos Geniculados/fisiologia , Som , Tálamo/citologia , Tálamo/diagnóstico por imagem
J Acoust Soc Am ; 139(6): EL246, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27369180


The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (± standard error of the mean) threshold for mistuning detection was 0.8 ± 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research.

Percepção Auditiva , Comportamento Animal , Sinais (Psicologia) , Furões/psicologia , Atividade Motora , Detecção de Sinal Psicológico , Estimulação Acústica , Animais , Vias Auditivas/fisiologia , Feminino , Furões/fisiologia , Psicoacústica , Tempo de Reação , Fatores de Tempo