Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model,Genes, Brain and Behavior

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Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2021-05-12 , DOI: 10.1111/gbb.12750
Kayla R Nygaard _{1,

2} , Raylynn G Swift _{1,

2} , Rebecca M Glick _{1,

2} , Rachael E Wagner ₂ , Susan E Maloney _{2,

3} , Georgianna G Gould ₄ , Joseph D Dougherty _{1,

2,

3}

Affiliation

Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, oxytocin (OT) dysregulation is hypothesized to be involved as some studies have shown elevated blood OT and altered OT receptor expression in patients. A “Complete Deletion” (CD) mouse, modeling the hemizygous deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These CD mice also exhibit impaired fear responses in the conditioned fear task. Here, we address whether OT dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an OT receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in CD mice. Thus, increased OT signaling is not acutely responsible for this phenotype. We also evaluated OT receptor and serotonin transporter availability in regions related to fear learning, memory and sociability using autoradiography in wild type and CD mice. While no differences withstood correction, we identified regions that may warrant further investigation. There was a nonsignificant decrease in OT receptor expression in the lateral septal nucleus and nonsignificant lowered serotonin transporter availability in the striatum and orbitofrontal cortex. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.

中文翻译：

催产素受体激活不会介导威廉姆斯综合症模型中的联想恐惧缺陷

威廉姆斯综合症会导致不同的行为表型，包括学习障碍、焦虑、恐惧症增加和过度社交。虽然驱动这部分表型的潜在机制尚不清楚，但假设催产素 (OT) 失调参与其中，因为一些研究表明患者血液 OT 升高和 OT 受体表达改变。一种“完全缺失”(CD) 小鼠模拟了威廉姆斯综合征中的半合子缺失，概括了人类存在的许多表型。这些 CD 小鼠在条件性恐惧任务中也表现出受损的恐惧反应。在这里，我们讨论 OT 失调是否是造成这种受损的联想恐惧记忆反应的原因。我们显示将 OT 受体拮抗剂直接递送至中枢神经系统并不能挽救 CD 小鼠中减弱的情境或提示恐惧记忆反应。因此，增加的 OT 信号并不是这种表型的直接原因。我们还使用野生型和 CD 小鼠的放射自显影评估了恐惧学习、记忆和社交能力相关区域中 OT 受体和血清素转运蛋白的可用性。虽然没有差异经得起校正，但我们确定了可能需要进一步调查的区域。外侧隔核中 OT 受体表达无显着降低，纹状体和眶额皮质中血清素转运蛋白可用性无显着降低。一起，

更新日期：2021-05-12

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