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

我们感知、移动、思考和记忆的能力来自于大脑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，进展缓慢，因为零件清单太长，零件本身太复杂。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，其中个体的大脑结构非常简单，研究得很好，可以非常详细地理解它们之间的相互作用。该项目的具体目标是定义从感觉处理的较高阶段到较低阶段的反馈或“向后”连接的功能，以及小脑和感觉处理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，但我们的知识是粗略的，也不足以设计治疗方法。通过在一个更简单的系统中提供有关这种相互作用的详细信息，该项目将作为理解更复杂系统（如人脑）中相互作用的基础。研究人员将利用本项目研究活动开发的资源，提高区域、国家和国际的科学素养和教育。凭借其易处理的电感觉和电刺激系统，莫米里德鱼已被证明是一个有价值的模型系统，连接结构和功能的神经回路。对电感觉叶（ELL）中的电感觉的第一处理阶段的研究已经产生了一个相当完整和经过充分测试的模型，在该模型中，实验测量形式的尖峰时间依赖性突触可塑性作用于描述良好的运动推论放电响应，以预测和抵消自我产生的感觉输入。解剖学研究已经绘制了中枢电感觉通路，行为学研究已经证明了复杂的电定位能力，这些能力可能取决于更高层次的神经处理。然而，需要对电感觉处理的更高阶段进行生理学研究，以将结构和功能联系起来。该项目的目标是提供第一个深入表征的中脑外侧束核（NL）-ELL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学，同时行为测量和电路操作。 拟议的实验将测试特定的假设NL功能，而在同一时间解决了一些一般性的问题，包括神经科学的多模态集成，功能的经常性反馈，和小脑在感觉处理的作用。

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.