Shiba Yoshiro, Santangelo Andrea M, Braesicke Katrin, Agustín-Pavón Carmen, Cockcroft Gemma, Haggard Mark, Roberts Angela C
Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK ; Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK.
Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK ; Department of Psychology, University of Cambridge Cambridge, UK.
Front Behav Neurosci. 2014 Apr 24;8:137. doi: 10.3389/fnbeh.2014.00137. eCollection 2014.
High trait anxiety is a risk factor for the development of anxiety disorders. Like the disorders themselves high trait anxiety has marked phenotypic variation at the level of symptomatology and neural circuits, suggesting that there may be different symptoms and distinct neural circuits associated with risk for these disorders. To address these issues, it is essential to develop reliable animal models of trait anxiety in a non-human primate whose brain bears structural and functional similarity to humans. The present study investigated individual variation in responsivity to fearful and anxiety provoking stimuli in the common marmoset monkey. Seven out of 27 animals failed to display discriminative, conditioned cardiovascular and behavioral responses on an auditory fear discrimination task, similar to that seen in high anxious humans and rodents. Their heightened emotionality to a rubber snake was consistent with the hypothesis that they were high in trait-like anxiety. Evidence for phenotypic variation in the high anxiety group was provided by the finding that discrimination failure was predicted early in conditioning by either hyper-vigilant scanning to the cues or a reduction in blood pressure to the context, i.e., test apparatus. Given that high trait anxiety in humans can be associated with altered prefrontal cognitive functioning and previously we implicated the marmoset anterior orbitofrontal (antOFC) and ventrolateral prefrontal cortex (vlPFC) in negative emotion regulation, we also tested the marmosets on two tests of cognitive flexibility differentially dependent on these two regions. While the high anxious group did not differ overall in their perseverative performance, the two distinct phenotypes were differentially correlated with reduced perseverative responding on the OFC- and vlPFC-dependent flexibility tests. Together, this study provides a new model of trait anxiety in marmosets amenable to analysis of phenotypic variation and neural circuitry.
高特质焦虑是焦虑症发展的一个风险因素。与这些疾病本身一样，高特质焦虑在症状学和神经回路水平上具有明显的表型变异，这表明可能存在与这些疾病风险相关的不同症状和独特神经回路。为了解决这些问题，在大脑结构和功能与人类相似的非人类灵长类动物中开发可靠的特质焦虑动物模型至关重要。本研究调查了普通狨猴对恐惧和焦虑诱发刺激反应性的个体差异。27只动物中有7只在听觉恐惧辨别任务中未能表现出有区别的、条件性心血管和行为反应，这与在高焦虑人类和啮齿动物中看到的情况类似。它们对橡胶蛇的情绪反应增强与它们具有高特质样焦虑的假设一致。高焦虑组表型变异的证据来自于这样的发现：在条件反射早期，辨别失败可由对线索的过度警惕扫描或对测试环境（即测试仪器）血压降低来预测。鉴于人类的高特质焦虑可能与前额叶认知功能改变有关，且之前我们认为狨猴眶额前皮质（antOFC）和腹外侧前额叶皮质（vlPFC）参与负性情绪调节，我们还在两项分别依赖于这两个区域的认知灵活性测试中对狨猴进行了测试。虽然高焦虑组在持续表现上总体没有差异，但这两种不同的表型在依赖于OFC和vlPFC的灵活性测试中与持续反应减少的相关性不同。总之，本研究提供了一种狨猴特质焦虑的新模型，适用于表型变异和神经回路分析。
