Neuronal mechanisms of multiplication and invariance

描述（由申请人提供）：本研究的长期目标是了解时变感觉刺激整合到单个神经元中的生物物理机制。当前的目标是提供详细的生物物理解释，说明单个神经元如何将两个输入相乘，以及它们如何实现对某些刺激属性的不变性。在脊椎动物和无脊椎动物的神经系统中，乘法已经涉及到许多神经计算，例如从视觉图像中提取运动信息。不变性是在高阶神经元中常见的属性，其选择性地响应于独立于其上下文的刺激特征。目前，人们对神经元如何完成这些计算还知之甚少。这些问题将在蝗虫的视觉系统中进行研究，蝗虫拥有一个神经元，即小叶巨型运动检测器（LGMD），它对在碰撞过程中出现的物体做出反应。这个神经元在撞击其树突的两个不同输入之间实现乘法运算，并表现出对隐约可见的物体的许多属性不变的响应。LGMD的许多特征使其成为生物物理研究的有利主题。该项目的具体目标是描述LGMD上突触输入的特性，包括背景突触活动在塑造其对迫在眉睫的刺激的反应中所起的作用。此外，几种活性膜电导的基本性质和它们在细胞树突树内突触输入整合中的作用也将被研究。还将评估视觉刺激期间LGMD树突隔室的时空激活模式。这些数据将用于建立细胞模型及其对迫在眉睫的刺激的反应。所采用的技术将包括刺激蝗虫复眼上的单个面-从而允许将复杂的视觉刺激分解为它们的基本组成部分-细胞内记录，药理学操作，钙成像和房室建模。该模型和实验数据将被用来确定在这个神经元的乘法和不变性的生物物理机制。由于在脊椎动物中枢神经系统中发现了非常相似的计算，因此该项目有望促进对乘法和不变性如何实现神经信息处理的一般理解。值得注意的是，乘法和不变性已被证明在视觉感知和注意力中发挥重要作用。因此，在这个模型系统中，表征生物物理和细胞机制的倍增和不变性也可能产生重要的见解，涉及感知和注意力障碍。公共卫生相关性本项目将在一个模型生物体中研究神经系统中常见的两种操作如何在单个神经元中实现：两个独立输入信号的乘法和对感官刺激特定属性的反应的不变性。乘法和不变性都被证明在视觉感知和注意力中起着重要作用。因此，表征倍增和不变性的生物物理和细胞机制可能会在涉及感知和注意力的疾病中产生重要的见解。

DESCRIPTION (provided by applicant): The long term objective of this research is to understand the biophysical mechanisms by which time-varying sensory stimuli are integrated in individual neurons. The immediate goal is to provide detailed biophysical explanations of how individual neurons multiply two inputs and how they implement invariance to certain stimulus attributes. Multiplication has been implicated in many neural computations, like the extraction of motion information from visual images, in both vertebrate and invertebrate nervous systems. Invariance is an attribute commonly found in higher order neurons that respond selectively to a stimulus feature independently of its context. Currently, there is little understanding of how these computations are accomplished by neurons. These issues will be investigated in the visual system of the locust, which possesses a neuron, the lobula giant movement detector (LGMD), that responds to objects looming on a collision course towards the animal. This neuron implements a multiplication operation between two distinct inputs impinging on its dendrites and exhibits responses that are invariant to many attributes of the looming object. Many features of the LGMD make it a favorable subject for biophysical studies. The specific aims of the project are to characterize the properties of synaptic inputs onto the LGMD, including the role played by background synaptic activity in shaping its responses to looming stimuli. In addition, the basic properties of several active membrane conductances and their role in the integration of synaptic inputs within the dendritic tree of the cell will be studied. The spatio-temporal activation pattern of the LGMD's dendritic compartments during visual stimulation will also be assessed. These data will be used to build a model of the cell and its response to looming stimuli. The techniques employed will include stimulation of single facets on the compound eye of the locust - thus allowing to decompose complex visual stimuli in their elementary components - intracellular recordings, pharmacological manipulations, calcium imaging and compartmental modeling. The model and experimental data will be used to identify the biophysical mechanisms underlying multiplication and invariance in this neuron. Because very similar computations are found in vertebrate central nervous systems, this project is expected to advance the general understanding of how multiplication and invariance are implemented for neural information processing. Notably, multiplication and invariance have been shown to play an important role in visual perception and attention. Thus, characterizing the biophysical and cellular mechanisms of multiplication and invariance in this model system may also yield important insights in disorders involving perception and attention. PUBLIC HEALTH RELEVANCE This project will study in a model organism how two operations commonly found in the nervous system are implemented within single neurons: the multiplication of two independent input signals and the invariance of responses to specific properties of sensory stimuli. Both multiplication and invariance have been shown to play an important role in visual perception and attention. Thus, characterizing the biophysical and cellular mechanisms of multiplication and invariance may yield important insights in disorders involving perception and attention.