Lateral septo-hypothalamic regulation of behavioral defense in the rat

恐惧也许是我们最原始的情感。对引发恐惧的情况的适应性行为反应促进了生存。错误的行为反应可能代价高昂。为了研究恐惧，我使用了一些测试，利用老鼠对厌恶、威胁情况的防御反应。所有动物，包括人类，对威胁都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攻击。但是大脑是如何选择最合适的生存反应的呢？根据一种理论，外侧隔膜评估来自海马体的传入感觉输入的情感相关性，并将该信息传递到下丘脑区域，下丘脑区域控制对生存重要的行为表达。侧隔接收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，关于侧隔和下丘脑是否一起工作来选择适当的恐惧相关行为，人们知之甚少。外侧隔的特定区域与特定的下丘脑核有独特的联系。我们最近的研究表明，外侧隔尾侧-外侧下丘脑回路影响大鼠对新颖/开放环境的防御反应，而外侧隔喙侧-前下丘脑回路影响它们对离散的、可定位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之间的信息流来进一步研究这种可能性。我可以通过向感兴趣的区域注射少量的muscimol（一种作用类似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老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技术，我可以确定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并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的一些变化提供一个总体框架，这些变化可能是人类病理性恐惧和焦虑障碍的基础。

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.