Synchronizing a Fear Regulation Circuit By Temporally Patterned Closed-LoopNeurostimulation

该项目将开发将两个大脑区域（边缘下皮层， IL和基底外侧杏仁核，BLA）。这个回路与恐惧和威胁反应有关，改变它可能会 改善恐惧调节。我们将通过脑电刺激来实现这一点， 严重精神疾病的新疗法使用大鼠作为临床前模型，我们希望证明我们可以 以一个频率改变两个特定的大脑区域，而不是像药物那样作用于整体的方法。 大脑一次。我们的假设是，连接将增加从“闭环”电刺激- 监控一个区域，当第一个区域变得活跃时刺激另一个区域。我们相信这将导致 两个区域紧密相连这应该意味着脑细胞的“集合”同步 IL和BLA之间的活性，特别是在θ（5-12 Hz）波段。 目的是开发可以改变大脑耦合的工具，然后测量这些工具的影响。 行为上的变化。对于大脑连接，我们将记录IL和BLA，并测量 这两个领域的活动相互关联。我们还将向每个区域注入电流， 另一个回答得多。对于行为，我们将使用条件反射范例，其中大鼠学习音调 预示着会有不愉快的电击然后我们将在老鼠 反复听到没有震动的音调，这个过程叫消光。如果我们的假设是正确的， 基于可塑性的刺激将使动物更能够记住这种新的“安全记忆”。 以后的日子。 我们将通过两个目标来实现这一目标。目标1是时域：我们将在一个 IL神经元放电的几毫秒增加。目标2是频域：我们将测量θ（5- 12 Hz）振荡，然后当IL θ达到临界相位时在BLA中用单脉冲刺激。 这两种技术应该以不同的方式改变IL-BLA连接，我们将测量其影响 电连接和防御行为。我们希望证明Aim 2的方法更好 增加θ波段的同步性通过研究多种类型的电气连接，我们希望 了解哪些因素对改变行为很重要。这最终应该与设计有关， 更好地治疗情绪和焦虑症。

This project will develop methods for linking together groups of cells in two brain areas (infralimbic cortex, IL, and basolateral amygdala, BLA). This circuit is related to fear and threat response, and changing it may improve fear regulation. We will do this with electrical brain stimulation, which has also shown promise as a new treatment for severe mental illness. Using rats as a pre-clinical model, we hope to show that we can alter two specific brain areas at a single frequency, as opposed to methods like drugs that act on the whole brain at once. Our Hypothesis is that connectivity will increase from "closed loop" electrical stimulation – monitoring one area and stimulating the other when the first becomes active. We believe this will cause the two areas to become strongly wired together. That should mean "ensembles" of brain cells synchronizing their activity between IL and BLA, especially in the theta (5-12 Hz) band. The Objective is to develop tools that can change brain coupling, then measure the effects of those changes on behavior. For brain connectivity, we will record IL and BLA and measure how strongly the activity in the two areas correlates. We will also inject electrical current into each area and measure how much the other responds. For behavior, we will use a conditioning paradigm where rats learn that a tone predicts an unpleasant electrical shock. We will then apply our electrical stimulations just before rats repeatedly hear the tone without the shock, a process called extinction. If our hypothesis is correct, our plasticity-based stimulations will make the animals more able to remember this new "safety memory" on later days. We will approach that Objective through two Aims. Aim 1 is time domain: we will make BLA active within a few milliseconds of an increase in IL neuron firing. Aim 2 is frequency domain: we will measure the theta (5- 12 Hz) oscillation in IL, then stimulate with single pulses in BLA when the IL theta reaches a critical phase. These two techniques should change IL-BLA connectivity in different ways, and we will measure the effects of both on electrical connectivity and defensive behavior. We expect to show that Aim 2's approach is better at increasing theta-band synchrony. By looking at multiple types of electrical connectivity, we hope to understand which ones matter for changing behaviors. That should ultimately be relevant for designing better treatments for mood and anxiety disorders.