Mechanisms for Internal Models in a Cerebellum-like Circuit

项目概要/摘要 人类和其他动物学习并存储控制其行为的因果关系的复杂模型 与世界的互动。这种内部模型可能对于转变模棱两可和延迟的问题至关重要。 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内部模型来完成，该模型可以预测 动物自身运动命令的感官后果。尽管它们对双方都有潜在的重要性 正常的大脑功能和神经系统疾病，事实证明理解内部模型如何 实际上是在神经回路中实现的。该更新提案采用了实验性和 模型系统（弱电鱼）的理论方法具有解决问题的独特优势 这个问题。我们之前对电鱼的研究成功地开发了详细的机械模型 电感觉叶 (ELL) 处理第一阶段的神经元如何预测并抵消 鱼自身器官放电（EOD）的影响。然而，这些研究认为高度简化 电传感系统面临的真正问题的版本。在自然条件下，电传感输入 时刻变化取决于鱼的运动（即电器官的位置） 尾巴与皮肤上的电感受器）以及 EOD 运动命令的时间模式 鱼。解决这个问题需要一个更复杂的内部模型，类似于那些被认为是在 哺乳动物的大脑。此外，过去的模型忽略了 ELL 电路的关键特征，例如 抑制性突触，可能发挥关键功能作用（在 ELL 和其他脊椎动物脑回路中）。由 针对这些问题，拟议的研究将为神经回路如何发挥作用提供一般见解 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链接 神经表征、明确的电路、突触可塑性和行为相关系统之间 水平功能。尽管建立这种联系是神经科学的一个主要目标，但在神经科学中的案例仍然相对较少。 它们实际上是可以制造的。

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.