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催产素受体表达于谷氨酸能前额皮质神经元,其选择性调节社会识别。

Oxytocin Receptors Are Expressed by Glutamatergic Prefrontal Cortical Neurons That Selectively Modulate Social Recognition.

机构信息

Department of Pharmacodynamics, College of Pharmacy.

Department of Psychiatry, College of Medicine.

出版信息

J Neurosci. 2019 Apr 24;39(17):3249-3263. doi: 10.1523/JNEUROSCI.2944-18.2019. Epub 2019 Feb 25.

Abstract

Social recognition, the ability to recognize individuals that were previously encountered, requires complex integration of sensory inputs with previous experience. Here, we use a variety of approaches to discern how oxytocin-sensitive neurons in the PFC exert descending control over a circuit mediating social recognition in mice. Using male mice with Cre-recombinase directed to the oxytocin receptor gene (), we revealed that oxytocin receptors (OXTRs) are expressed on glutamatergic neurons in the PFC, optogenetic stimulation of which elicited activation of neurons residing in several mesolimbic brain structures. Optogenetic stimulation of axons in the BLA arising from OXTR-expressing neurons in the PFC eliminated the ability to distinguish novel from familiar conspecifics, but remarkably, distinguishing between novel and familiar objects was unaffected. These results suggest that an oxytocin-sensitive PFC to BLA circuit is required for social recognition. The implication is that impaired social memory may manifest from dysregulation of this circuit. Using mice, we demonstrate that optogenetic activation of the neurons in the PFC that express the oxytocin receptor gene () impairs the ability to distinguish between novel and familiar conspecifics, but the ability to distinguish between novel and familiar objects remains intact. Subjects with autism spectrum disorders (ASDs) have difficulty identifying a person based on remembering facial features; however, ASDs and typical subjects perform similarly when remembering objects. In subjects with ASD, viewing the same face increases neural activity in the PFC, which may be analogous to the optogenetic excitation of oxytocin receptor (OXTR) expressing neurons in the PFC that impairs social recognition in mice. The implication is that overactivation of OXTR-expressing neurons in the PFC may contribute to ASD symptomology.

摘要

社交识别,即识别之前遇到过的个体的能力,需要将感觉输入与先前的经验进行复杂的整合。在这里,我们使用多种方法来辨别 PFC 中的催产素敏感神经元如何对介导小鼠社交识别的回路施加下行控制。使用具有定向到催产素受体基因 (Cre-recombinase) 的雄性小鼠 (),我们揭示了 PFC 中的催产素受体 (OXTR) 表达在谷氨酸能神经元上,光遗传学刺激这些神经元会引发几个中脑边缘脑结构中的神经元激活。光遗传学刺激来自 PFC 中 OXTR 表达神经元的 BLA 中的轴突消除了区分新异和熟悉同种动物的能力,但引人注目的是,区分新异和熟悉物体的能力不受影响。这些结果表明,催产素敏感的 PFC 到 BLA 回路是社交识别所必需的。这意味着社交记忆受损可能是由于该回路的失调而表现出来的。使用小鼠,我们证明光遗传学激活表达催产素受体基因 () 的 PFC 中的神经元会损害区分新异和熟悉同种动物的能力,但区分新异和熟悉物体的能力保持不变。患有自闭症谱系障碍 (ASD) 的受试者在基于记忆面部特征来识别个体方面有困难;然而,在记忆物体方面,ASD 和典型受试者的表现相似。在 ASD 受试者中,观看相同的面孔会增加 PFC 中的神经活动,这可能类似于光遗传学刺激 PFC 中表达催产素受体 (OXTR) 的神经元,从而损害小鼠的社交识别能力。这意味着 PFC 中 OXTR 表达神经元的过度激活可能导致 ASD 症状。

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