Midbrain electrosensory processing in a mormyrid fish: multimodal integration, recurrent feedback, and cerebellar influence

我们感知、移动、思考和记忆的能力源于大脑中神经元网络之间的相互作用。神经科学研究试图理解这种相互作用。然而，在许多情况下，由于零件清单太长，零件本身太复杂，进展缓慢。这个项目利用了一种不寻常的动物——一种能发出自己电场的鱼，它的个体大脑结构非常简单，研究得很透彻，可以非常详细地理解它们之间的相互作用。这个项目的具体目标是定义从感觉加工的高到低阶段的反馈或“向后”连接的功能，以及小脑和感觉加工区域之间的连接的功能。反馈和小脑连接被认为对人类的感觉处理至关重要，并与自闭症等神经系统疾病有关，但我们的知识很粗略，在设计治疗方法方面也不够充分。通过提供简单系统中这种相互作用的详细信息，该项目将为理解更复杂系统（如人脑）中的相互作用奠定基础。研究者将利用从本项目研究活动中开发的资源来提高地区、国家和国际的科学素养和教育。由于其易于控制的电感觉和电运动系统，海马已被证明是连接神经回路结构和功能的有价值的模型系统。对电感觉叶（ELL）中电感觉的第一加工阶段的研究已经产生了一个相当完整且经过良好测试的模型，其中实验测量的依赖于脉冲时间的突触可塑性形式作用于描述良好的运动必然放电反应，以预测和抵消自产生的感觉输入。解剖学研究已经绘制了中央电感觉通路，行为学研究已经证明了复杂的电定位能力可能依赖于更高水平的神经处理。然而，需要对电感觉加工的更高阶段进行生理学研究，以将结构和功能联系起来。该项目的目标是首次深入表征中脑外侧支核（NL），这是ELL之后的下一个主要处理阶段。研究人员的方法将包括清醒准备中的细胞内和细胞外电生理，同时行为测量和电路操作。拟议的实验将测试有关NL功能的特定假设，同时解决神经科学中的一些一般问题，包括多模态整合、循环反馈功能和小脑在感觉处理中的作用。

Our ability to perceive, move, think, and remember arises from interactions between networks of neurons in the brain. Neuroscience research seeks to understand such interactions. However, in many cases, progress has been slow because the parts list is too long and the parts themselves are too complex. This project takes advantage of an unusual animal--a fish that emits its own electrical field, in which the individual brain structures are sufficiently simple and well-studied that their interactions can be understood in great detail. Specific goals of this project are to define the function of feedback or "backward" connections from higher to lower stages of sensory processing as well as the function of connections between the cerebellum and sensory processing regions. Feedback and cerebellar connections are believed to be critical for sensory processing in humans and have been implicated in neurological disorders such as autism, but our knowledge is sketchy and insufficient or designing treatments. By providing detailed information about such interactions in a simpler system, this project will serve as a foundation for understanding interactions in more complex systems such as the human brain. The investigator will use the resources developed from this project's research activities to improve science literacy and education regionally, nationally, and internationally. By virtue of their tractable electrosensory and electromotor systems mormyrid fish have proven to be a valuable model system for linking structure and function in neural circuits. Studies of the first processing stage for the electrosense in the electrosensory lobe (ELL) have produced a fairly complete and well-tested model in which an experimentally measured form of spike timing-dependent synaptic plasticity acts on well-described motor corollary discharge responses to predict and cancel out self-generated sensory inputs. Anatomical studies have mapped central electrosensory pathways and behavioral studies have documented sophisticated electrolocation abilities that likely depend on higher-level neural processing. However physiological studies of higher stages of electrosensory processing are needed to link structure and function. The goal of this project is to provide the first in depth characterization of the midbrain lateral toral nucleus (NL)--the next major processing stage after ELL. The investigators' approach will include intracellular and extracellular electrophysiology in awake preparations, simultaneous behavioral measurements, and circuit manipulations. Proposed experiments will test specific hypotheses regarding NL function while at the same time addressing a number of general issues in neuroscience including multimodal integration, functions of recurrent feedback, and roles of the cerebellum in sensory processing.