Lateral septo-hypothalamic regulation of behavioral defense in the rat

恐惧或许是我们最原始的情感。对引发恐惧的情况做出适应性行为反应可以提高存活率。错误的行为反应可能代价高昂。为了研究恐惧，我使用测试来挖掘老鼠对令人厌恶、威胁的情况的防御反应。所有动物，包括人类，都对威胁表现出一系列适应性防御反应，从提高警惕和风险评估到逃跑和防御性攻击。但是大脑如何选择最适合生存的反应呢？根据一种理论，外侧隔评估从海马体传入的感觉输入的情绪相关性，并将这些信息传递到控制对生存重要的行为表达的下丘脑区域。外侧隔区接受来自海马体的大量输入，大量证据证实这两个结构与恐惧有关。然而，关于外侧隔核和下丘脑是否共同选择适当的恐惧相关行为，我们所知的要少得多。外侧隔的特定区域与特定的下丘脑核团有独特的联系。我们最近的工作表明，外侧隔尾侧-下丘脑外侧回路影响大鼠对新的/开放环境的防御反应，而外侧隔头-下丘脑前部回路影响大鼠对离散的、局部的威胁刺激的防御反应。我计划通过有选择地中断各个电路上的信息流来进一步研究这种可能性。我可以通过向感兴趣区注射少量的麝香酚(一种类似于GABA的药物)来关闭每个回路的特定部分，然后观察这些局部注射如何改变大鼠对各种引发恐惧的情况的防御反应。通过使用免疫组织化学的技术，我可以确定这些回路的一些神经化学特征。这些实验的结果将对大脑如何处理有关威胁的信息和产生适当的防御行为提供更全面的理解。更广泛地说，这项工作将为理解大脑中可能导致人类病理性恐惧和焦虑症的一些变化提供一个总体框架。

Fear is perhaps our most primal emotion. Adaptive behavioral responses to fear-provoking situations promote survival. The wrong behavioral response can be costly. To study fear, I use tests that tap into rats' defensive responses to aversive, threatening situations. All animals, including humans, exhibit a spectrum of adaptive defensive responses to threat, ranging from increased vigilance and risk-assessment to escape and defensive attack. But how does the brain select the most appropriate response for survival? According to one theory, the lateral septum evaluates the emotional relevance of incoming sensory input from the hippocampus and conveys this information on to hypothalamic areas that control the expression of behaviors important to survival. The lateral septum receives massive input from the hippocampus, and extensive evidence confirms that those two structures contribute to fear. However, far less is known about whether the lateral septum and hypothalamus work together to select appropriate fear-related behaviors. Specific regions of the lateral septum are uniquely connected to specific hypothalamic nuclei. Our recent work suggests that the lateral septum caudal-lateral hypothalamic circuit influences rats' defensive responses to novel/open environments, whereas the lateral septum rostral-anterior hypothalamic circuit influences their defensive responses to discrete, localizable threat stimuli. I plan to further investigate this possibility by selectively interrupting the flow of information across the individual circuits. I can turn off specific parts of each circuit by injecting small amounts of muscimol (a drug that acts like GABA) into the area of interest and then observe how these local injections change rats' defensive responses to a variety of fear-provoking situations. By using techniques from immunohistochemistry, I can determine some of the neurochemical characteristics of the circuits. The results of these experiments will provide a fuller understanding into how the brain processes information about threats and produces appropriate defensive behavior. More broadly, this work will provide a general framework for understanding some of the changes in brain that might underlie pathological fears and anxiety disorders in humans.