EXPERIENCE AND DECISION-MAKING IN A REAL NEURAL NETWORK

虽然在阐明感觉处理和运动模式生成的神经基础方面已经取得了巨大的进展，但对运动程序启动的机制知之甚少。运动程序启动是决定特定行为是否发生的决策过程。这个话题很有意思，既是因为决策是任何神经系统执行的最高级别的功能之一，也因为许多神经系统疾病明确地破坏了我们启动行为的能力。第一个具体目标将测试一组三个假设，这些假设是关于海洋软体动物Tritonia diomedea如何决定是否开始逃逸游泳以应对厌恶的刺激。该项目旨在确定导致动物高静息行为阈值的电路机制，特别是感官输入如何克服这一阈值并启动持续的行为反应。第二个具体目标将考察决策中最有趣的方面之一背后的机制--过去的经验可以强烈影响下一次机会出现时启动特定行为的可能性。该项目将试图确定两种形式的非联想学习--习惯化和敏感化--如何作用于具体目标1中描述的阈值机制，从而使决策以一种方式与另一种方式相比较。敏感化训练使Tritonia更有可能游泳，而习惯化训练使其不太可能。该项目还将研究脉冲前抑制(PPI)的细胞基础，这是一种行为可塑性的形式，无害的前刺激可以防止或减少通常由强测试刺激引发的行为反应。PPI的缺陷被认为是精神分裂症的一些认知障碍的基础，因此PPI的生理基础引起了人们的极大兴趣。这些实验将测试初步数据表明，PPI是由突触前抑制介导的可能性，这些抑制直接作用于游泳回路的前四个层次--正是这些元素与三叉神经节的决策关系最大。每个目标都将采用电生理学和真实计算机模拟相结合的方法。

While tremendous progress has been made in elucidating the neural bases of sensory processing and motor pattern generation, far less is known about the mechanismws underlying motor program initiation-the decision-making process that determines whether a particular behavioral act will occur. This topic is of considerable interest, both because decision-making is one of the highest-level functions performed by any nervous system, and because a number of neurological diseases specifically disrupt our ability to initiate behavior. The first Specific Aim will test a set of three hypotheses about how the marine mollusc, Tritonia diomedea, decides whether or not to initiate an escape swim in response to an aversive stimulus. The project aims to identify the circuit mechanisms responsible for the animal's high resting behavioral threshold, and in particular, how sensory input acts to overcome this threshold and initiate a sustained behavioral response. The second Specific Aim will examine the mechanisms underlying one of the most interesting aspects of decision-making-the fact that past experience can strongly influence the likelihood that a particular behavior will be initiated the next time opportunity presents itself. The project will attempt to determine how two forms of nonassociative learning, habituation and sensitization, act on the threshold mechanisms described in Specific Aim 1 to bias decision-making one way versus another. Sensitization training makes Tritonia more likely to swim, while habituation training makes it less likely. The project will also investigate the cellular basis of prepulse inhibition (PPI), a form of behavioral plasticity in which an innocuous pre-stimulus prevents or reduces the behavioral response normally elicited by a strong test stimulus. Deficits in PPI have been suggested to underlie some of the cognitive disturbances in schizophrenia, thus the physiological basis of PPI is of considerable interest. The experiments will test the possibility, suggested by preliminary data, that PPI is mediated by presynaptic inhibition directed onto the first four hierarchical levels of the swim circuit-the very elements that have the most to do with decision-making in Tritonia. Each aim will employ the combined methodologies of electrophysiology and realistic computer simulations.