Biophysical mechanisms and computational principles of weak signal detection.

神经密码的性质是神经科学的基本问题之一。要理解感觉系统的神经编码，既需要指定外部信号和由此产生的棘波序列之间的映射，也需要证明下游神经电路可以解释或解码这种映射，从而指导行为输出。通过将电生理学、建模和药理学结合起来，我想在细胞水平上明确了解下游神经元是如何执行对时间神经编码的解码的。弱电鱼类锥体细胞中微弱信号的检测是研究这一问题的一个很好的模型。神经解剖学研究已经彻底描述了电感觉回路的网络连通性。对PC的输入神经元(初级传入)进行了电生理学研究和非常详细的建模。使用相对简单的模型系统(例如，与哺乳动物皮层相比)将使我能够将细胞编码机制与特定的感觉任务联系起来，例如放大微弱信号。该项目将由三个主要要素组成：1)使用细胞外记录确定PC针对弱信号的神经元代码；2)使用这些数据开发将主要传入代码转换为PC代码的细胞动力学模型；3)使用该模型对解码的细胞基础做出强有力的预测，并通过细胞内记录和药物操作来测试这些预测。由于PC突触输入放大的细胞基础(例如，AMPA、NMDA和GABA受体加上各种电压门控离子通道)在所有哺乳动物的感觉系统中都被发现，I将开发的解码算法应该是普遍适用的，研究其他系统的神经科学家将能够评估它是通过视觉、听觉或躯体感觉系统的突触动力学实现的。

The nature of the neural code is one of the fundamental questions in neuroscience. Understanding the neural code for sensory systems requires both specifying a map between external signals and the resulting spike trains and demonstrating that downstream neural circuits can interpret or decode this mapping and therefore direct behavioral output. By combining electrophysiology, modeling and pharmacology I want to understand explicitly on a cellular level how decoding of a temporal neural code is performed by downstream neurons. Weak signal detection in pyramidal cells (PC) of weakly electric fish is an excellent model to study this question. Neuroanatomical work has thoroughly described the network connectivity of the electrosensory circuits. The input neurons (primary afferents) to PCs have been investigated electrophysiologically and modeled in great detail. Using a relatively simple model system (e.g. as compared to mammalian cortex) will enable me to link cellular coding mechanisms to a specific sensory task, e.g. amplification of weak signals. The project will consist of three major elements: 1) determining the neuronal code of PCs for weak signals using extracellular recordings; 2) using these data to develop a model of the cellular dynamics that transforms the primary afferent code into the PC code; 3) using the model to make strong predictions as to the cellular basis of decoding and testing these predictions by intracellular recordings and pharmacological manipulations. Since the cellular basis of PC synaptic input amplification (e.g. AMPA, NMDA and GABA receptors plus various voltage-gated ion channels) is found in all mammalian sensory systems, the decoding algorithm I will develop should be generally applicable and neuroscientists working on other systems will be able to evaluate whether it is realized by the synaptic dynamics in the visual, auditory or somatosensory system.