期刊
NEUROPHARMACOLOGY
卷 165, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2019.107931
关键词
Autism; Prefrontal cortex; Synapse; E/I balance; Serotonin; Interneuron; 5-HT2 receptor
资金
- MEXT KAKENHI [16H06316, 16H06463, S0801035]
- Japan Science and Technology Agency (Core Research for Evolutional Science and Technology)
- MEXT
The prefrontal cortex (PFC) has been extensively studied in autism spectrum disorder (ASD) in an attempt to understand the deficits in executive and other higher brain functions related to sociability and emotion. Disruption of the excitatory/inhibitory (E/I) balance of cortical circuits is thought to underlie the pathophysiology of ASD. Recently, we showed that 15q dup mice (a model for ASD with human chromosome 15q11-13 paternal duplication) exhibit disruption of the E/I balance in layer 2/3 pyramidal neurons of the somatosensory cortex due to a decrease in the number of inhibitory synapses. However, whether there is a pathological abnormality in E/I balance in the PFC of 15q dup mice remains unknown. In this study, we found that 15q dup facilitates the activity-induced LTP of glutamate synapses onto layer 5 pyramidal neurons by shifting the E/I balance to an excitatory state, which this was associated with differences in synaptic glutamatergic and GABAergic inputs onto GABAergic fast-spiking interneurons (FSINs). Furthermore, we found that FSIN excitability was well-modulated and regulated by the constitutive activation of 5-HT 2 receptors in PFC microcircuits. These results provide new insights into the cellular mechanisms underlying maintenance of optimal E/I balance in the PFC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据