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。神经科学研究试图了解这种相互作用。然而，在许多情况下，进展缓慢，因为零件列表太长，零件本身太复杂。这个项目利用了一种不同寻常的动物--一种会发出自己的电场的鱼，在这种动物中，个体的大脑结构足够简单和得到充分的研究，可以非常详细地了解它们之间的相互作用。该项目的具体目标是确定从感觉加工的高级阶段到低级阶段的反馈或“反向”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，并与自闭症等神经疾病有关，但我们的知识粗略、不足或设计治疗方法。通过在一个更简单的系统中提供关于这种相互作用的详细信息，该项目将成为理解更复杂系统(如人脑)中相互作用的基础。研究人员将利用该项目研究活动开发的资源，在区域、国家和国际范围内提高科学素养和教育水平。由于其易于处理的电感觉和电动马达系统，Mormyid FISH已被证明是连接神经电路中结构和功能的一个有价值的模型系统。对电感觉叶(ELL)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，一种实验测量的依赖于棘波时序的突触可塑性作用于描述良好的运动必然放电反应，以预测和抵消自我产生的感觉输入。解剖学研究描绘了中枢电感觉通路，行为研究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高级阶段进行生理学研究，以将结构和功能联系起来。这个项目的目标是提供第一个深入的中脑外侧核团(NL)的特征--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学、同步行为测量和电路操作。拟议的实验将测试关于NL功能的具体假设，同时解决神经科学中的一些一般问题，包括多模式整合、经常性反馈的功能，以及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.