CRCNS: Cortical network models of taste processing: dynamics and plasticity

描述（申请人提供）：研究人员将结合实验研究和计算模拟来揭示味觉处理的神经基础。在此过程中，他们将提供对感觉加工更一般方面的见解，如试验间可变性的因果关系，注意力对皮层活动的作用，以及先前美味的物质在与恶心单一联系后变得不美味的条件反射机制。这些研究将使用模拟来评估在一个尺度上的变异性如何在正常的皮质功能中增强或减少更大尺度上的变异性。这些研究还将使用模型和模拟来揭示神经元网络中连接或细胞特性的哪些变化会导致味觉学习中对感官刺激的行为反应发生改变。味觉是解决感官处理问题的重要方式，尽管尚未得到充分利用，因为它与行为和生存有很强的联系，可以产生强大、快速而持久的学习。此外，最近研究人员发现，在味觉处理过程中，神经活动的变化与动物的注意力状态有关。研究人员将测试这些依赖注意力的神经活动变化是如何产生的，并将使用模拟来评估这些变化可能的功能作用。这项研究的一个变革性作用将是改变人们看待试验间可变性的明显随机性的方式。作者的目的不是在观察神经数据时造成麻烦，而是表明这种可变性是神经活动的一个方面，既可以提供有关潜在活动的信息，又有利于神经处理的某些方面。理解噪音、可变性和振荡与注意力的调节将有助于解决感官加工所有领域的缺陷。更具体地说，这些关于大脑过程如何决定一种味道是令人满意的，而另一种味道是有害的的研究可能具有广泛的临床意义，例如，治疗某些形式的肥胖和减轻化疗引起的儿童味觉障碍。此外，我们对正常皮层活动及其由注意力（通过神经调节剂或大脑的执行区域）调节的理解的提高将有助于我们更好地解决皮层异常活动的问题，如癫痫和与精神分裂症相关的执行控制障碍。

DESCRIPTION (provided by applicant): The investigators will combine experimental studies with computational simulations to uncover the neural underpinnings of taste processing. In so doing, they will provide insight into more general facets of sensory processing, such as the cause and effect of trial-to-trial variability, the role of attentiveness on cortical activity and the mechanisms of conditioning whereby a previously palatable substance is rendered unpalatable following a single association with nausea. These studies will use simulations to assess how variability at one scale can either enhance or reduce variability at a larger scale during normal cortical functioning. The studies will also use models and simulations, to uncover what changes in connections or cellular properties in a network of neurons lead to the altered behavioral response to a sensory stimulus seen in taste learning. Taste is an important, though underutilized, modality for addressing issues of sensory processing, since it has a strong connection to behavior and survival and can produce strong, rapid yet long-lasting learning. Moreover, recently the investigators have uncovered correlated changes of neural activity with the state of attentiveness of an animal during taste processing. The investigators will test how these attention-dependent changes of neural activity arise and will use simulations to assess the possible functional role of such changes. A transformative role of the research will be to change the way the apparent randomness of trial-to-trial variability is viewed. Rather than being a nuisance in the observation of neural data, the authors aim to show that such variability is an aspect of neural activity that can both provide information about underlying activity and be beneficial for some aspects of neural processing. An understanding of the modulation of noise, variability and oscillations with attentiveness will be beneficial for addressing deficiencies in all areas of sensory processing. More specifically, these investigations of what brain processes are involved in making one tastant highly desirable and another noxious may have far-flung clinical implications for, for instance, the treatment of some forms of obesity and the alleviation of childhood taste disorders caused by chemotherapy. Furthermore, an improvement in our understanding of normal cortical activity and its modulation by attention (via neuromodulators or by executive areas of the brain) will help us better address problems of abnormal cortical activity such as epilepsy and disorders of executive control associated with schizophrenia.