Lateral septo-hypothalamic regulation of behavioral defense in the rat

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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.