Effects of expectation on gustatory cortex activity

描述（由申请人提供）：根据动物是清醒还是麻醉，大脑处理感觉刺激的方式不同。在麻醉的动物中，没有内部认知活动影响大脑，因此刺激被被动地接受，并仅根据其物理特性进行编码。另一方面，在清醒的受试者中，对刺激的反应受到持续的心理过程（即注意力、期望）的严重调节。例如，同样的刺激，根据动物的预期，会有不同的解释：例如，人类和他们的大脑——导致预期温和的味道，可能会被“愚弄”，认为苦味比实际味道更温和。本提案旨在研究这种现象的神经基础：特别是，这里概述的实验将解决预期在多大程度上影响大脑的背景活动和对感官刺激的反应。味觉刺激固有的奖励/厌恶性质以及动物生存中食物选择的重要性，使味觉成为直接研究神经和行为层面预期效应的理想感觉系统。提出的实验将在清醒的大鼠中进行；单个神经元的集合将通过植入已知与味觉和期望有关的区域（GC，眶额皮质[OFC]，杏仁核[AM]）的多个电极来记录。期望的两个不同方面将被研究：对未知刺激的一般期望（一个有点类似于注意的过程）和对已知刺激的特定期望。首先，老鼠将接受训练，通过按下杠杆来对声音做出反应，从而收集一种味道。在这个范例中，音调不会提供任何关于味道的信息——它只会触发与未知刺激的预期相关的注意力转移。另一方面，对特定刺激的预期将在另一组实验中得到解决，这些实验涉及使用两种音调，每种音调都与不同的味道具体相关。在这些实验中，听觉线索将提供有关预期的特定味道的信息。自发活动，对预期线索的反应，以及对意外和预期口味的反应将被记录下来，以分析一般和特定期望对味道的影响。最后，电极也将植入OFC和AM -两个已知与期望有关的区域-这两个区域与GC之间的关系将在上述实验条件下进行研究。了解内部状态（如期望）在多大程度上影响感觉反应是感觉神经科学领域的一个核心问题。对大脑如何对口味预期作出反应的理解，将揭示包括人类在内的所有哺乳动物食物选择的复杂性，并将提供可能应用于肥胖和饮食失调研究的重要信息。这一建议旨在了解味觉刺激预期的神经基础。期望在食物的感知和评价中起着重要作用（Deliza和MacFie 1996； Hurling和Shepherd 2003）；因此，这一主题对与公共卫生有关的问题具有重要意义，例如食物喜好和选择选择。此外，了解预期的神经基础与安慰剂的神经机制研究有关（Nitschke et al. 2006a; Nitschke et al. 2006b; Sarinopoulos et al. 2006）——这是神经科学中一个日益增长的兴趣领域（Petrovic et al. 2005; Ploghaus et al. 1999）。

DESCRIPTION (provided by applicant): The brain processes sensory stimuli differently depending on whether an animal is awake or anesthetized. In anesthetized animals no internal cognitive activity influences the brain, and so stimuli are passively received and coded solely for their physical properties. In awake subjects, on the other hand, responses to stimuli are heavily modulated by ongoing mental processes (i.e. attention, expectation). The same stimulus, for instance, is interpreted differently depending on what the animal expects: humans - and their brains - led to expect a mild taste, for instance, can be "fooled" into thinking that a bitter taste is milder than it actually is. The present proposal is designed to study the neural underpinnings of such phenomena: in particular, the experiments outlined here will address the extent to which expectation influences background activity of the brain and responses to sensory stimuli. The intrinsic rewarding/aversive nature of gustatory stimuli and the importance of food selection for animal survival make taste an ideal sensory system for directly studying the effects of expectation at both the neural and behavioral level. The experiments proposed will be conducted in awake rats; ensembles of single neurons will be recorded with multiple electrodes implanted in areas known to be involved in taste and expectation (GC, orbitofrontal cortex [OFC], amygdala [AM]). Two different aspects of expectation will be investigated: generic expectation of an unknown stimulus (a process somewhat analogous to attention) and specific expectation of a known stimulus. For the first, rats will be trained to collect a taste by pressing a lever in response to a tone. In this paradigm, the tone will not provide any information regarding the identity of the taste-it will simply trigger an attentional shift related to the expectation of an unknown stimulus. Expectation of a specific stimulus, on the other hand, will be addressed in another subset of experiments involving the use of two tones, each specifically associated with a different taste. In these experiments, the auditory cues will provide information about the specific taste anticipated. Spontaneous activity, responses to anticipatory cues, and responses to unexpected and expected tastes will be recorded to parse the effects of generic and specific expectation on taste. Finally, electrodes will be implanted also in OFC and AM - two areas known to be involved in expectation - and the relationship between these two areas and GC will be studied in the experimental conditions described above. Understanding the degree to which internal states, such as expectation, shape sensory responses is a central question in the field of sensory neuroscience. The comprehension of how the brain responds to the expectation of tastes will shed light on the complexities of food selection choices of all mammals - including humans - and will provide important information which could potentially be applied to the study of obesity and eating disorders. This proposal is designed to understand the neural underpinnings of expectation of taste stimuli. Expectation plays an important role in the perception of food and in its evaluation (Deliza and MacFie 1996; Hurling and Shepherd 2003); as such, this subject has important implications on issues relevant to public health, such as food liking and selection choices. Additionally, understanding the neural basis of expectation is relevant for the study of the neural mechanisms of placebo (Nitschke et al. 2006a; Nitschke et al. 2006b; Sarinopoulos et al. 2006) - a growing field of interest in neuroscience (Petrovic et al. 2005; Ploghaus et al. 1999).