The role of zinc signalling in the amygdala

我们不断地将效价归因于我们在浏览环境时遇到的感官信息，它是令人愉快的和有益的还是有害的和令人厌恶的？我们学会预测与这些经历相关的积极和消极结果，并做出适当的情绪和行为反应，以获得奖励并逃避/避免危险。这对我们的生存至关重要。大脑的一个区域，杏仁核基底外侧复合体（BLA），接收密集的感觉输入，并且已知是编码刺激效价所必需的。BLA中的神经元将投射发送到大脑的其他区域，这些区域负责做出适当的行为反应，并形成对厌恶事件和奖励关联的记忆。我的实验室感兴趣的是理解特定于情绪的信息在这些大脑区域中处理和传递的信号机制。 我们已经发现，BLA包含大量的神经元，这些神经元独特地使用锌作为神经递质。我们还看到，在这些神经元靶向的大脑区域，它们的突触中有非常高水平的锌，这表明锌的信号传导对这些神经元连接的正常功能很重要。本提案中概述的实验旨在评估锌信号是否对BLA神经元形成的回路中情感相关信息的处理至关重要。 我们最近获得了一种经过基因工程改造的小鼠，使我们能够选择性地靶向使用锌作为神经递质的神经元，用可见标记物标记它们，使用光激活通道增加或减少它们的活性，以及消除它们使用锌传递信号的能力。我们将分析这些小鼠的行为，同时以特定于电路的方式操纵特定锌神经元的活动，同时控制它们释放锌的能力，同时它们暴露于阴性或阳性实验环境。通过这种方式，我们将能够理解锌神经元，它们在大脑中形成的回路，以及它们传递的锌信号，如何有助于杏仁核处理情感相关信息的功能。 我把我的大部分学术生涯都投入到研究中，旨在了解含锌神经元的作用，以及锌作为哺乳动物大脑中的神经递质。作为世界上锌神经生物学的专家之一，获得这种革命性的基因工程小鼠为我提供了应用新的、最先进的细胞、生理、分子和遗传技术的手段，以更好地理解锌信号在大脑功能中的基本作用。

We are constantly attributing valence to sensory information that is encountered as we navigate our environment is it pleasant and rewarding or noxious and aversive? We learn to predict positive and negative outcomes that are tied to those experiences, and make appropriate emotional and behavioural responses, to approach rewards and to escape/avoid danger. This is essential for our survival. One region of the brain, the basolateral complex of the amygdala (BLA), receives dense sensory inputs and is known to be necessary for encoding stimulus valence. Neurons in the BLA send projections to other regions of the brain that are responsible for making appropriate behavioural responses and for forming memories for aversive events and reward associations. My laboratory is interested in understanding the signaling mechanisms whereby valence-specific emotional information is processed and conveyed among these brain regions. We have discovered that the BLA contains a large number of neurons that uniquely use zinc as a neurotransmitter. We also see that in regions of the brain that are targeted by these neurons, they have very high levels of zinc in their synapses, suggesting that signaling by zinc is important for the normal function of connections made by these neurons. The experiments outlined in this proposal are directed toward assessing whether zinc signaling is critical for processing of emotionally relevant information, in circuits formed by BLA neurons. We have recently acquired a strain of mouse that has been genetically engineered to allow us to selectively target neurons that use zinc as a neurotransmitter, to label them with a visible marker, increase or decrease their activity using light-activated channels, as well as to eliminate their ability to convey a signal using zinc. We will analyze the behaviour of these mice while manipulating the activity of specific zinc neurons in a circuit-specific manner, at the same time controlling their ability to release zinc, while they are exposed to negative or positive experimental contexts. In this way we will be able to understand how zinc neurons, the circuits they form in the brain, and the zinc signals that they transmit, contribute to the function of the amygdala in processing emotionally relevant information. I have devoted the majority of my academic life engaged in studies directed to understanding the role of zinc containing neurons, and zinc as a neurotransmitter in the mammalian brain. As one of the world's experts in zinc neurobiology, the acquisition of this revolutionary, genetically-engineered mouse provides me with the means to apply novel, state-of-the-art cellular, physiological, molecular and genetic techniques to developing a greater understanding of the fundamental role of zinc signaling in brain function.