Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, Massachusetts 02115.
Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, Massachusetts 02115.
eNeuro. 2024 Oct 3;11(10). doi: 10.1523/ENEURO.0179-23.2024. Print 2024 Oct.
Despite decades of preclinical investigation, there remains limited understanding of the etiology and biological underpinnings of anxiety disorders. Sensitivity to potential threat is characteristic of anxiety-like behavior in humans and rodents, but traditional rodent behavioral tasks aimed to assess threat responsiveness lack translational value, especially with regard to emotionally valenced stimuli. Therefore, development of novel preclinical approaches to serve as analogues to patient assessments is needed. In humans, the fearful face task is widely used to test responsiveness to socially communicated threat signals. In rats, ultrasonic vocalizations (USVs) are analogous social cues associated with positive or negative affective states that can elicit behavioral changes in the receiver. It is therefore likely that when rats hear aversive alarm call USVs (22 kHz), they evoke translatable changes in brain activity comparable with the fearful face task. We used functional magnetic resonance imaging in male and female rats to assess changes in BOLD activity induced by exposure to aversive 22 kHz alarm calls emitted in response to threatening stimuli, prosocial (55 kHz) USVs emitted in response to appetitive stimuli, or a computer-generated 22 kHz tone. Results show patterns of regional activation that are specific to each USV stimulus. Notably, limbic regions clinically relevant to psychiatric disorders (e.g., amygdala, bed nucleus of the stria terminalis) are preferentially activated by either aversive 22 kHz or appetitive 55 kHz USVs. These results support the use of USV playback as a promising translational tool to investigate affective processing under conditions of distal threat in preclinical rat models.
尽管经过了几十年的临床前研究，但人们对焦虑症的病因和生物学基础仍知之甚少。对潜在威胁的敏感是人类和啮齿动物焦虑样行为的特征，但传统的旨在评估威胁反应的啮齿动物行为任务缺乏转化价值，尤其是在涉及情绪性刺激时。因此，需要开发新的临床前方法来模拟患者评估。在人类中，恐惧面孔任务被广泛用于测试对社交传达的威胁信号的反应能力。在大鼠中，超声发声（USVs）是与积极或消极情绪状态相关的类似社交线索，可以引起接收者的行为变化。因此，当大鼠听到厌恶的警报声 USVs（22 kHz）时，它们可能会引发与恐惧面孔任务相当的可翻译的大脑活动变化。我们使用功能磁共振成像技术在雄性和雌性大鼠中评估了暴露于厌恶的 22 kHz 警报声（响应威胁刺激）、响应奖赏刺激的社交性 55 kHz USVs 或计算机生成的 22 kHz 音调引起的 BOLD 活动变化。结果显示出与每种 USV 刺激特异性相关的区域激活模式。值得注意的是，与精神障碍相关的边缘区域（例如杏仁核、终纹床核）被厌恶的 22 kHz 或奖赏的 55 kHz USVs 优先激活。这些结果支持使用 USV 回放作为一种有前途的转化工具，在临床前大鼠模型中研究远距离威胁条件下的情感处理。
