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

对感官刺激的行为反应会根据内部和外部因素，包括以往的经验和刺激类型，以灵活的方式变化。即使是像药用水蛭这样简单的生物，在神经元和行为反应上也会发生活动依赖性的变化。在由一个水蛭神经节和一块体壁组成的半完整制剂中，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，有时甚至是游泳。这些行为反应是由神经节中400个实验可获得的、单独表征的神经元的子集控制的。我们之前的研究表明，T（触觉）细胞是最敏感的机械感受器，在引发触觉刺激的行为反应中起着重要作用。此外，我们得出结论，T细胞至少有一个尖峰起始区用于编码皮肤的触觉刺激，一个用于处理靠近体细胞的突触输入。此外，我们确定了一种细胞内在的可塑性机制，它可以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备中进行实验。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了网络活动和肌肉运动的行为。在我们的“重放实验”中，触觉皮肤刺激与体细胞电流注入对T细胞交替进行，引发与前一次触觉刺激完全相同的T细胞尖峰序列，而不诱导其他机械感受器的活动。比较这两种情况使我们能够确定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态外，我们将在大量T细胞刺激导致细胞内在可塑性后进行相同的分析。本项目分为四个子项目，以以下假设为指导：1。细胞水平：在多个尖峰起始区发生的细胞内在可塑性机制的相互作用导致不同计算任务相对影响的灵活转变（即皮肤附近的感觉编码与细胞体附近的突触整合）。行为层面：T细胞对的相对尖峰时间，被证明编码触摸位置，被网络解码以控制局部弯曲。网络水平：当皮肤被触摸时，T细胞尖峰首先激活预备网络，然后形成局部弯曲反应。各级：T细胞反应的活动依赖性灵活性驱动行为灵活性。通过这些实验，我们以水蛭为例，确定了细胞内在可塑性对神经元行为控制的影响。

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.