■自闭症患者的情感识别和感觉处理受损。然而,没有结合这些症状的自闭症小鼠模型,从而限制了对自闭症中情感识别和感觉加工之间关系的探索以及所涉及的分子机制。
■使用Negr1-/-鼠标,我们进行了情感状态辨别测试和气味习惯/排泄物测试。使用k均值聚类方法分析数据。我们还采用了全细胞膜片钳和溴脱氧尿苷掺入测定法来研究潜在的机制。
■当遇到暴露于束缚压力或慢性疼痛的小鼠时,野生型小鼠通过接近压力小鼠或避免痛苦的小鼠来区分它们,而Negr1-/-小鼠与它们表现出无偏见的社交互动。接下来,我们证明了野生型和Negr1-/-小鼠在实验环境中都使用它们的嗅觉进行社交互动,但是Negr1-/-小鼠表现出异常的嗅觉习惯和对社交气味的厌恶。在电生理学研究中,与野生型小鼠相比,Negr1-/-小鼠对嗅球二尖瓣细胞的抑制性输入增加,随后他们的兴奋性下降。作为一种潜在的潜在机制,我们发现Negr1-/-小鼠脑室下区的成年神经发生减少,这导致嗅球中新产生的抑制性神经元的整合减少。
■NEGR1有助于鼠标情感识别,可能通过调节嗅觉神经发生和随后的嗅觉感觉处理。我们提出了一种基于成人嗅觉神经发生中断的自闭症相关行为的新神经生物学机制。
情感歧视缺陷是自闭症谱系障碍的主要症状之一,其分子/细胞机制尚待探索。这里,我们证明了Negr1缺陷型自闭症相关小鼠与情感激发的小鼠没有表现出优先的社会互动(即,压力和疼痛),并显示其与其他小鼠的异常嗅觉处理有关。作为潜在的潜在细胞机制,我们发现成年出生的神经元减少,嗅球区域的兴奋性/抑制性失衡。这些结果表明,对Negr1和嗅觉处理的作用的进一步研究可以为自闭症的分子和细胞机制提供有价值的见解。
UNASSIGNED: Affective recognition and sensory processing are impaired in people with autism. However, no mouse model of autism comanifesting these symptoms is available, thereby limiting the exploration of the relationship between affective recognition and sensory processing in autism and the molecular mechanisms involved.
UNASSIGNED: With Negr1 -/- mice, we conducted the affective state discrimination test and an odor habituation/dishabituation test. Data were analyzed using the k-means clustering method. We also employed a whole-cell patch clamp and bromodeoxyuridine incorporation assay to investigate underlying mechanisms.
UNASSIGNED: When encountering mice exposed to restraint stress or chronic pain, wild-type mice discriminated between them by either approaching the stressed mouse or avoiding the painful mouse, whereas Negr1 -/- mice showed unbiased social interactions with them. Next, we demonstrated that both wild-type and Negr1 -/- mice used their olfaction for social interaction in the experimental context, but Negr1 -/- mice showed aberrant olfactory habituation and dishabituation against social odors. In electrophysiological studies, inhibitory inputs to the mitral cells in the olfactory bulb were increased in Negr1 -/- mice compared with wild-type mice, and subsequently their excitability was decreased. As a potential underlying mechanism, we found that adult neurogenesis in the subventricular zone was diminished in Negr1 -/- mice, which resulted in decreased integration of newly generated inhibitory neurons in the olfactory bulb.
UNASSIGNED: NEGR1 contributes to mouse affective recognition, possibly by regulating olfactory neurogenesis and subsequent olfactory sensory processing. We propose a novel neurobiological mechanism of autism-related behaviors based on disrupted adult olfactory neurogenesis.
A deficit in affective discrimination is one of the major symptoms of autism spectrum disorder, the molecular/cellular mechanisms of which have yet to be explored. Here, we demonstrated that Negr1-deficient autism-relevant mice did not show preferential social interaction with affectively provoked mice (i.e., stress and pain) and showed its association with aberrant olfactory processing for other mice. As a potential underlying cellular mechanism, we found a decrease in adult-born neurons and excitatory/inhibitory imbalance in the olfactory bulb region. These results suggest that further investigation into the role of Negr1 and olfactory processing could provide valuable insights into molecular and cellular mechanisms of autism.