The role of non-canonical neural codes in behavior

项目摘要/摘要 (与资助父母奖不变)信息处理依赖于神经元放电率的想法 (速率编码)长期以来一直是神经生物学的中心教条。然而，其他非规范编码方案 (时间码和模拟码)已经被提出来承载有意义的信息，并且更加计算化 比速率编码更强大。重要的是，该领域一直缺乏强大的遗传模型系统来解开非 规范的编码过程，我通过在果蝇中定义两个神经回路来解决这个缺口 用于研究时间和模拟代码。我发现时间编码是昼夜节律的基础 在果蝇DN1p时钟神经元中睡眠，而模拟的和潜在的“混合”(模拟尖峰) 在果蝇DA-Wed摄食神经元中，编码被用来实现轴突特异性饥饿处理。 作为一个模型系统来理解尖峰时间代码如何影响分子信号和行为，我们 将重点放在具有特定尖峰模式的果蝇DN1p时钟神经元上，通过 突触可塑性的新形式，SPDP(棘波模式依赖可塑性)。为了研究分子过程 对于SPDP形成，我们将首先描述不规则尖峰内的时间结构的基本元素 DN1p中的模式，以及确定其生物物理来源。接下来，我们将研究分子机制 它们作用于突触前尖峰模式的下游，将电信号转换为生化反应。 我们还将利用果蝇遗传学的力量来描绘 DN1ps突触中的SPDP。 作为一个理解非尖峰神经元编码如何影响信号和行为的模型系统，我们将 重点研究具有局部可塑性的果蝇DA-Wed摄食神经元，以控制蛋白质饥饿行为。神经 编码范例通常侧重于“数字”的、要么全有要么全无的基于峰值的模型。在哺乳动物中，纯净 “模拟”编码发生在视网膜上，但最近的研究表明，模拟信号调制基于脉冲的信号 在海马区和大脑皮层发出信号(“混合”编码)。然而，这些编码在神经中的作用 可塑性和行为仍不清楚。我们最近发现“编码蛋白质”的轴突分支，但不是 “糖编码”轴突分支表现出DA-WEB摄食的亚阈值膜电位波动 神经元，在轻微的蛋白质剥夺之后。在严重的蛋白质缺乏之后，这样的模拟信号相互作用 通过尖峰事件产生“混合”加工，以实现更强和更持久的蛋白质喂养 行为。因此，我们将研究调节“模拟”和“混合”信号的分子过程以及如何 “混合”编码可能是局部分支特异性可塑性的基础。总而言之，这些使用果蝇的研究 DN1p时钟神经元和DA-Wed摄食神经元应阐明非规范的基本原理 神经密码，确定这些神经密码在长期行为和可塑性中的作用，并确定它们的 潜在的分子机制。

Project Summary/Abstract (Unchanged from the funded parent award) The idea that information processing depends on neuronal firing rate (rate coding) has long been a central dogma in neurobiology. However, other non-canonical coding schemes (temporal and “analog” codes) have been proposed to carry meaningful information and be more computationally powerful than rate coding. Importantly, the field has lacked powerful genetic model systems to disentangle non- canonical coding processes, and I addressed this gap by defining two neural circuits in Drosophila that can be used to study temporal and analog codes. I found that temporal coding underlies the circadian regulation of sleep in the Drosophila DN1p clock neurons, whereas analog and potentially “hybrid” (analog + spiking) codes are used to achieve axon-specific hunger processing in Drosophila DA-WED feeding neurons. As a model system to understand how spiking temporal codes impact molecular signaling and behavior, we will focus on Drosophila DN1p clock neurons having specific spiking patterns to control sleep quality through a novel form of synaptic plasticity, SPDP (Spike Pattern Dependent Plasticity). To examine the molecular process of SPDP formation, we will first characterize essential elements of the temporal structures within irregular spiking patterns in DN1ps, as well as identify their biophysical origins. Next, we will investigate molecular mechanisms that act downstream of presynaptic spiking patterns to transform electrical signals into biochemical responses. We will also leverage the power of Drosophila genetics to delineate the entire molecular pathway required for SPDP in DN1ps synapses. As a model system to understand how nonspiking neuronal codes impact signaling and behavior, we will focus on Drosophila DA-WED feeding neurons having local plasticity to control protein hunger behavior. Neural coding paradigms have generally focused on “digital” all-or-none spike-based models. In mammals, pure “analog” coding occurs in the retina, but recent work has shown that analog signaling modulates spike-based signaling (“hybrid” coding) in the hippocampus and cortex. However, the function of these codes in neural plasticity and behavior remains unclear. We recently discovered that the “protein coding” axonal branch, but not the “sugar coding” axonal branch, exhibits sub-threshold membrane potential fluctuations of DA-WED feeding neurons, following mild protein deprivation. Following severe protein deprivation, such analog signaling interacts with spiking events to generate “hybrid” processing to achieve stronger and longer-lasting protein feeding behavior. Thus, we will study the molecular processes mediating “analog” and “hybrid” signaling and how “hybrid” codes may underlie localized branch-specific plasticity. In conclusion, these studies using Drosophila DN1p clock neurons and DA-WED feeding neurons should elucidate fundamental principles for non-canonical neural codes, determine the role of these neural codes in long-lasting behaviors and plasticity, and identify their underlying molecular mechanisms.