RESUMO
Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Assuntos
Animais , Humanos , Camundongos , Modelos Animais de Doenças , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Camundongos Knockout , Neurônios/metabolismoRESUMO
Objective: To study whether the orientation behavior of rats is affected by multi-sensory information. Methods: SD rats were randomly divided into 2 groups: the audio-visual integration group and pure audio group. The orientation behaviors of rats were observed after given single modal and multi-modal sensory cues with spatial disparities. Results: We found that when the temporal and spatial audio cues were coincident to a target visual cue, the rats had a markedly reduced reaction time and increased success rate in orientation behaviors; there was an obvious audio-visual integration effect. The integration effect was more obvious when the intensity of target visual cue was weak, with the enhancement efficiency being (87.3 ± 8.5)%, significantly higher than that when the intensity of target visual cue was stronger (27.6%, P< 0.05). Conclusion: Rat auditory-visual integration behaviors also follow the multi-sensory integration rules.
RESUMO
Objective:To study whether the orientation behavior of rats is affected by multi-sensory information.Methods: SD rats were randomly divided into 2 groups:the audio-visual integration group and pure audio group.The orientation behaviors of rats were observed after given single modal and multi-modal sensory cues with spatial disparities.Results:We found that when the temporal and spatial audio cues were coincident to a target visual cue,the rats had a markedly reduced reaction time and increased success rate in orientation behaviors;there was an obvious audio-visual integration effect.The integration effect was more obvious when the intensity of target visual cue was weak,with the enhancement efficiency being(87.3?8.5)%, significantly higher than that when the intensity of target visual cue was stronger(27.6%,P