Synaptic mechanisms of amygdala-dependent behaviors

杏仁核通过分析传入的信息并触发防御反应来运作。我们研究的第一个问题是，杏仁核如何在突触水平上区分来自大脑不同区域的信号，那些处理感觉信息的信号，以及那些提供执行控制的信号。为了解决这个问题，人们需要通过有选择地刺激来自特定大脑区域的纤维来询问特定的输入。为了解决这个问题，我们建立了基于视蛋白的技术，选择性地激活或抑制杏仁核的输入，这些输入来自传递感觉信息的皮质区TEA和与影响、疼痛和认知有关的前扣带皮质。这两种输入以相同的杏仁核神经元为目标，并混合在杏仁核内。我们发现这两条通路在突触可塑性方面存在显著差异。虽然从周边皮质传入的长时程增强突触传递(LTP)需要抑制GABAA受体介导的抑制，但ACC-杏仁核通路中的LTP不需要。此外，切断外囊和杏仁核之间的联系，即使在GABAA受体介导的抑制存在的情况下，也能使来自周边皮质的LTP进入。此外，我们发现这两种输入与杏仁核抑制神经元的连接方式不同。ACC能更有效地激活表达5-羟色胺受体3的中间神经元，而TEA能更有效地招募囊周细胞。这些发现具有有趣的意义：首先，外囊的多巴胺依赖的抑制神经元似乎在杏仁核周围皮质的输入中通向可塑性，而基底外侧核内的5-羟色胺依赖的中间神经元则通向来自ACC的高度精炼的信息。 我们目前的目标是确定相同的杏仁核输入如何调节自由活动动物的恐惧行为。此外，我们正在研究杏仁核中间神经元如何控制传入的感觉信息，并在防御反应的产生中做出贡献。

Amygdala operates by analyzing incoming information and triggering defensive responses. The first question of our investigation is how amygdala distinguishes, at the synaptic level, between signals which arrive from different areas of the brain, those which process sensory information, and those which provide executive control. To address this question, one needs to interrogate a specific input by selectively stimulating fibers coming from a specific brain area. To address this question we established opsin-based techniques for selective activation or silencing of amygdala inputs from cortical area TeA which transmits sensory information, and from the anterior cingulate cortex, which is implicated in affect, pain and cognition. Both inputs target same amygdala neurons and are intermingled inside amygdala. We found significant difference in synaptic plasticity between the two pathways. While long-term potentiation of synaptic transmission (LTP) in the input from perirhinal cortex required suppression of GABAa receptor-mediated inhibition, LTP in the ACC-amygdala pathway did not. Moreover, severing connections between external capsule and amygdala enabled LTP in the input from perirhinal cortex even in the presence of GABAa receptor-mediated inhibition. In addition, we found that these two inputs exhibit differential connectivity to the amygdala inhibitory neurons. The ACC input was more effective in activating interneurons that express serotonin receptor 3, whereas the TeA input was more effective in recruiting the pericapsular cells. These findings have interesting implications: first, dopamine-dependent inhibitory neurons of the external capsule appear to gate plasticity in the amygdala input from perirhinal cortex, whereas serotonin-dependent interneurons inside the basolateral nucleus gate the highly refined information from ACC. Our current goal is to determine how the same amygdala inputs modulate fear behaviors in free-moving animals. In addition, we are investigating how amygdala interneurons gate the incoming sensory information and contribute in generation of defensive response.