Mechanisms for Internal Models in a Cerebellum-like Circuit

项目摘要/摘要 人类和其他动物学习和存储支配人类行为的因果关系的复杂模型 与世界的互动。这样的内部模型可能对转换模棱两可和延迟的内容至关重要 感官数据转化为稳定的感知和协调的运动。例如，区分外部 来自那些自我产生的感觉输入可以通过一个内部模型来完成，该模型预测 动物自身运动指令的感官后果。尽管它们对双方都具有潜在的重要性 正常的大脑功能和神经障碍，事实证明，理解内部模型是如何 实际上是在神经电路中实现的。这项续签提案结合了试验性和 具有独特优势的模型系统--弱电鱼类--的理论方法 这个问题。我们以前对电鱼的研究成功地开发了一个详细的机械模型 关于神经元在电感觉叶(ELL)处理的第一阶段如何预测和抵消 鱼自身的电子器官放电(EOD)的影响。然而，这些研究认为高度简化的 电感系统面临的真正问题的版本。在自然条件下，电感觉输入 根据鱼的运动(即，电子器官在体内的位置)而变化 尾巴与皮肤上的电感受器)以及由EOD发出的运动指令的时间模式 鱼。解决这个问题需要一个更复杂的内部模型，类似于被认为是在 哺乳动物的大脑。此外，过去的模型忽略了ELL电路的关键特性，例如 抑制性突触，可能在ELL和其他脊椎动物的大脑回路中扮演关键的功能角色。通过 针对这些问题，拟议的研究将提供对神经回路如何起作用的一般见解 以区分自身产生的刺激和外部刺激。拟议的研究还将提供直接联系 在神经表征、明确定义的回路、突触可塑性和行为相关系统之间 级别函数。尽管建立这样的联系是神经科学的主要目标，但在 它们实际上是可以制造出来的。

Project Summary/Abstract Humans and other animals learn and store sophisticated models of the causal relationships that govern their interactions with the world. Such internal models are likely critical for transforming ambiguous and delayed sensory data into stable perceptions and coordinated movements. For example, distinguishing external sensory input from those that are self-generated could be accomplished via an internal model that predicts the sensory consequences of an animal’s own motor commands. Despite their potential importance for both normal brain function and neurological disorders, it has proven challenging to understand how internal models are actually implemented in neural circuits. This renewal proposal applies a combination of experimental and theoretical approaches to a model system—the weakly electric fish—with unique advantages for addressing this question. Our previous studies of electric fish were successful in developing a detailed mechanistic model of how neurons at the first stage of processing in the electrosensory lobe (ELL) predict and cancel out the effects of the fish’s own electric organ discharge (EOD). However, these studies considered a highly simplified version of the true problem facing the electrosensory system. Under natural conditions, electrosensory inputs vary moment-to-moment depending both on the movements of the fish (i.e. the position of the electric organ in the tail versus electroreceptors on the skin) and the temporal pattern of EOD motor commands emitted by the fish. Solving this problem requires a more complex internal model, akin to those believed to be generated in the mammalian brain. In addition, past models ignored key features of ELL circuitry, such as plasticity of inhibitory synapses, which likely play key functional roles (both in ELL and in other vertebrate brain circuits). By addressing these issues the proposed research will provide general insights into how neural circuits contribute to distinguishing self-generated from external stimuli. The proposed studies will also provide direct links between neural representations, well-defined circuitry, synaptic plasticity, and a behaviorally relevant systems level function. Though forging such links is a primary goal of neuroscience, there are still relatively few cases in which they can actually be made.