神经科学
生物
海马结构
海马体
血清素转运体
锥体细胞
树突棘
索马
神经发育
自闭症
心理学
血清素
发展心理学
基因
遗传学
受体
作者
Roberto De Gregorio,Galadu Subah,Jennifer C Chan,Luisa Speranza,Xiaolei Zhang,Aarthi Ramakrishnan,Li Shen,Ian Maze,Patric K Stanton,Ji Y. Sze
摘要
ABSTRACT Neurodevelopmental disorders ranging from autism to intellectual disability display sex-biased prevalence and phenotypical presentations. Despite increasing knowledge about temporospatial cortical map development and genetic variants linked to neurodevelopmental disorders, when and how sex-biased neural circuit derailment may arise in diseased brain remain unknown. Here, we identify in mice that serotonin uptake transporter (SERT) in non-serotonergic neurons – hippocampal and prefrontal pyramidal neurons – confers sex-biased effects specifically during neural circuit development. A set of gradient-patterned CA3 pyramidal neurons transiently express SERT to clear extracellular serotonin, coinciding with hippocampal synaptic circuit establishment. Ablating pyramidal neuron SERT (SERTPyramidΔ) alters dendritic spine developmental trajectory in the hippocampus, and precipitates sex-biased impairments in long-term activity-dependent hippocampal synaptic plasticity and cognitive behaviors. Transcriptomic analyses identify sex-biased alterations in gene sets associated with autism, dendritic spine structure, synaptic function and male-specific enrichment of dysregulated genes in glial cells in early postnatal SERTPyramidΔ hippocampus. Our data suggest that SERT function in these pyramidal neurons underscores a temporal- and brain region-specific regulation of normal sex-dimorphic circuit development and a source for sex-biased vulnerability to cognitive and behavioral impairments. This article has an associated ‘The people behind the papers’ interview.
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