Impact of cell-intrinsic plasticity on the neuronal control of behavior

细胞内在可塑性对神经元行为控制的影响

• 批准号: 450070471
• 负责人: Professorin Dr. Jutta Kretzberg
• 金额: --
• 依托单位: Arbeitsgruppe Computational Neuroscience
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/450070471?language=en
• 关键词: Impact; cell; intrinsic; plasticity; neuronal

Behavioral responses to sensory stimuli change in a flexible way depending on both internal and external factors, including previous experience and stimulation types. Even simple organisms like the medicinal leech feature activity-dependent changes in neuronal and behavioral responses. The cellular basis of stimulus avoidance behaviors can be studied well in in a semi-intact preparation consisting of one leech ganglion and a piece of the body wall. Light touch usually causes the body wall to bend away locally, and sometimes even swimming. These behavioral responses are controlled by subsets of the 400 experimentally accessible, individually characterized neurons in the ganglion. Our previous studies suggest that T (touch) cells, the most sensitive mechanoreceptors, play a major role in eliciting behavioral responses to tactile stimulation. Moreover, we concluded that a T cell has at least one spike initiation zone for encoding tactile stimulation of the skin and one for processing synaptic inputs close to the soma. Furthermore, we identified a cell-intrinsic plasticity mechanism which alters spiking patterns depending on previous activity.To identify how cell-intrinsic plasticity influences the control of behavior, we plan to perform experiments in semi-intact body wall preparations. Simultaneously to intracellular T cell double recordings, we record the network activity with voltage-sensitive dyes and the muscle movement of the resulting behavior. In our “replay experiments”, tactile skin stimulation is alternated with the somatic current injection to the pair of T cells, eliciting exactly the same T cell spike trains as the preceding touch stimulus, without inducing activity of the other mechanoreceptors. Comparing the two conditions allows us to identify the impact of T cell spiking on network activity and behavioral responses. In addition to the steady-state with long recovery time between stimuli, we will perform the same analysis after massive T cell stimulation that causes cell-intrinsic plasticity. The project is structured into four sub-projects, guided by the following hypotheses:1. Cellular level: The interaction of cell-intrinsic plasticity mechanisms occurring at multiple spike-initiation zones causes a flexible shift in the relative impact of different computational tasks (i.e. sensory coding near the skin vs. synaptic integration near the cell body).2. Behavioral level: The relative spike timing of T cell pairs, which was shown to encode touch location, is decoded by the network to control local bending.3. Network level: When the skin is touched, T cell spikes first activate the preparatory network and later shape the local bending response.4. All levels: The activity-dependent flexibility of T cell responses drives behavioral flexibility.With these experiments, we identify the impact of cell-intrinsic plasticity on the neuronal control of behavior for the example of the leech.

对感觉刺激的行为反应根据内部和外部因素，包括先前的经验和刺激类型，以一种灵活的方式改变。即使是像药用水蚤这样的简单生物体，神经元和行为反应也会出现依赖活动的变化。在由一个水蛭神经节和一段体壁组成的半完整的准备中，可以很好地研究刺激回避行为的细胞基础。轻触通常会导致体壁局部弯曲，有时甚至会游泳。这些行为反应由神经节中400个可通过实验获得的独立特征神经元的子集控制。我们以前的研究表明，T(触摸)细胞是最敏感的机械感受器，在诱发对触觉刺激的行为反应中发挥着重要作用。此外，我们得出结论，T细胞至少有一个用于编码皮肤触觉刺激的棘波起始区，以及一个用于处理靠近胞体的突触输入的刺激区。此外，我们确定了一种细胞内在可塑性机制，它根据先前的活动改变尖峰模式。为了确定细胞内在可塑性如何影响行为控制，我们计划在半完整的体壁制剂中进行实验。同时对细胞内T细胞进行双重记录，我们用电压敏感染料记录网络活动以及由此产生的肌肉运动行为。在我们的“重放实验”中，触觉皮肤刺激与体细胞电流注入T细胞对交替进行，引发与前一次触摸刺激完全相同的T细胞尖峰序列，而不会诱导其他机械感受器的活动。通过比较这两种情况，我们可以确定T细胞尖峰对网络活动和行为反应的影响。除了刺激之间恢复时间较长的稳定状态外，我们还将在大规模T细胞刺激后进行同样的分析，这会导致细胞内在可塑性。该项目在以下假设的指导下被分成四个子项目：1.细胞水平：发生在多个棘波起始区的细胞内在可塑性机制的相互作用导致不同计算任务(即皮肤附近的感觉编码与细胞体附近的突触整合)的相对影响的灵活转移。行为水平：T细胞对的相对尖峰时间被网络解码以控制局部弯曲，该时间被显示为编码触摸位置。网络层面：当皮肤被触摸时，T细胞尖峰首先激活准备网络，然后形成局部弯曲反应。所有层面：T细胞反应的活性依赖的灵活性驱动行为灵活性。通过这些实验，我们以水蚤为例，确定了细胞内在可塑性对神经元行为控制的影响。