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由微小RNA调控的神经递质转换控制社交偏好的变化。

Neurotransmitter Switching Regulated by miRNAs Controls Changes in Social Preference.

作者信息

Dulcis Davide, Lippi Giordano, Stark Christiana J, Do Long H, Berg Darwin K, Spitzer Nicholas C

机构信息

Neurobiology Section, Division of Biological Sciences and Center for Neural Circuits and Behavior, Kavli Institute for Brain and Mind, University of California San Diego, La Jolla, CA 92093-0357, USA; Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093-0603, USA.

Neurobiology Section, Division of Biological Sciences and Center for Neural Circuits and Behavior, Kavli Institute for Brain and Mind, University of California San Diego, La Jolla, CA 92093-0357, USA.

出版信息

Neuron. 2017 Sep 13;95(6):1319-1333.e5. doi: 10.1016/j.neuron.2017.08.023. Epub 2017 Aug 31.

Abstract

Changes in social preference of amphibian larvae result from sustained exposure to kinship odorants. To understand the molecular and cellular mechanisms of this neuroplasticity, we investigated the effects of olfactory system activation on neurotransmitter (NT) expression in accessory olfactory bulb (AOB) interneurons during development. We show that protracted exposure to kin or non-kin odorants changes the number of dopamine (DA)- or gamma aminobutyric acid (GABA)-expressing neurons, with corresponding changes in attraction/aversion behavior. Changing the relative number of dopaminergic and GABAergic AOB interneurons or locally introducing DA or GABA receptor antagonists alters kinship preference. We then isolate AOB microRNAs (miRs) differentially regulated across these conditions. Inhibition of miR-375 and miR-200b reveals that they target Pax6 and Bcl11b to regulate the dopaminergic and GABAergic phenotypes. The results illuminate the role of NT switching governing experience-dependent social preference. VIDEO ABSTRACT.

摘要

两栖类幼体社会偏好的变化源于持续暴露于亲属气味剂。为了解这种神经可塑性的分子和细胞机制,我们研究了嗅觉系统激活对发育过程中副嗅球(AOB)中间神经元神经递质(NT)表达的影响。我们发现,长期暴露于亲属或非亲属气味剂会改变表达多巴胺(DA)或γ-氨基丁酸(GABA)的神经元数量,同时吸引力/厌恶行为也会相应改变。改变多巴胺能和GABA能AOB中间神经元的相对数量,或局部引入DA或GABA受体拮抗剂,会改变亲属偏好。然后,我们分离出在这些条件下差异调节的AOB微小RNA(miR)。对miR-375和miR-200b的抑制表明,它们靶向Pax6和Bcl11b以调节多巴胺能和GABA能表型。这些结果阐明了神经递质转换在调控经验依赖性社会偏好中的作用。视频摘要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7539/5893310/c2a24dd42528/nihms954226f1.jpg

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