Combining electrophysiology and behavioural tests to explore cellular and molecular mechanisms of behaviour and learning

弄清哺乳动物大脑中的行为和行为可塑性是如何产生的，是现代神经科学面临的主要挑战之一。我们将把体外电生理学与体内行为和药理学试验结合起来，以探索行为和学习背后的细胞和分子机制。我们使用一个建立良好的简单模型——哺乳动物惊吓反应——以便能够将细胞事件与行为联系起来。惊吓反应是由一条短而清晰的主要通路介导的，它很容易被量化，并受到感觉门控机制、情绪和学习的调节。一个突出的内在惊吓调节是对惊吓刺激重复呈现的习惯。习惯化被认为是最重要的学习任务之一，我们在日常生活中都在不知不觉中进行习惯化学习。在完善了关于惊吓反应的中枢通路的知识之后，我们现在对惊吓调节的细胞机制感兴趣。我们能够确定啮齿动物惊吓反应短期习惯化的细胞机制：初级惊吓通路内的次级感觉神经元在重复激活后会受到突触抑制。基于此，我们的研究目标是证明突触抑制和习惯化密切相关。我们进一步想要完全了解导致突触抑制并最终习惯化的分子过程。此外，我们想要确定不同的神经递质受体和通路，它们能够干扰惊吓通路，因此是介导感觉门控和情绪对惊吓的影响的候选人。我们的工作将首次全面描述哺乳动物的学习任务，这将有助于显著推进关于人类和动物大脑如何产生行为和行为可塑性的基本知识。

It is one of the major challenges for modern Neuroscience to find out how behaviour and behavioural plasticity is generated in the mammalian brain. We will combine in vitro electrophysiology with behavioural and pharmacological tests in vivo in order to explore cellular and molecular mechanisms underlying behaviour and learning. We use a well established simple model - the mammalian startle response - in order to be able to connect cellular events to behaviour. The startle response is mediated by a short and well described primary pathway, it can easily be quantified and it is modulated by sensory gating mechanisms, emotions and learning. One prominent intrinsic startle modulation is habituation to the repeated presentation of startle stimuli. Habituation is considered one of the most essential learning tasks and we all perform habituation learning throughout our daily life without noticing it.After refining the knowledge about the central pathway that mediates startle responses, we are now interested in cellular mechanisms of startle modulations. We were able to identify the cellular mechanism presumably underlying short-term habituation of startle responses in rodents: secondary sensory neurons within the primary startle pathway are subject to synaptic depression upon repeated activation. Based on this, the goal of our studies is to demonstrate that synaptic depression and habituation are closely realted. We further want to completely understand the molecular processes that lead to synaptic depression and eventually to habituation. In addition, we want to identify different neurotransmitter receptors and pathways that are able to interfere with the startle pathway and are therefore candidates to mediate sensory gating and emotional effects on startle. Our work will provide the first comprehensive description of a mammalian learning task and it will help to significantly advance the basic knowledge about how human and animal brains generate behaviour and behavioural plasticity.