Effects of expectation on gustatory cortical 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和系统基础：特别是，这里概述的实验将解决预期影响大脑背景活动和对感官刺激的反应的程度。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多个电极植入已知与味觉和期望有关的连接区域（GC，眶额皮质[OFC]，基底外侧杏仁核[BLA]）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，老鼠将被训练通过按下一个杠杆来响应一个声音来收集味道。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涉及使用两种音调的实验中得到解决，每一种音调都与按下杠杆时不同味道的可用性有关。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。两个行为任务将用于研究特定期望的不同方面：第一个任务，一个音调提示可获得的美味（蔗糖或氯化钠），另一个音调提示在杠杆下的惩罚（奎宁），将揭示对具有相反情感价值的特定口味的预期的影响。第二个任务是两个音调，两个杠杆任务，其中每个音调都与特定杠杆上可用的味道相关联，它依赖于具有相似适口性的味道。本课题将专门研究具有相似情感价值但不同化学特性的刺激的期望效应。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在GC， OFC和BLA中记录，以分析一般和特定期望对味觉加工的影响。最后，在上述实验条件下，在OFC和BLA植入颅内插管，研究这两个区域在调节GC活性中的作用。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。

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 and systems 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 connected areas known to be involved in taste and expectation (GC, orbitofrontal cortex [OFC], basolateral amygdala [BLA]). 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 tastes 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 the availability of a different taste at a press of a lever. In these experiments, the auditory cues will provide information about the specific taste anticipated. Two behavioral tasks will be used to study different aspects of specific expectation: the first task, a go/no-go in which one tone cues the availability of a palatable taste (sucrose or NaCl) and the other a punishment (quinine) at a press of a lever, will reveal the effects of expectation of particular tastes having opposite affective value. The second task, a two tone, two levers task in which each tone is associated with a taste available at a specific lever, relies on tastes with similar palatability. This task will specifically address the effects of expectation for stimuli with similar affective value but different chemical identity. Spontaneous activity, responses to anticipatory cues, and responses to unexpected and expected tastes will be recorded in GC, OFC and BLA to parse the effects of generic and specific expectations on taste processing. Finally, intracranial cannulae will be implanted in OFC and BLA and the contribution of these two areas in modulating GC activity will be studied for 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. PUBLIC HEALTH RELEVANCE: This proposal is designed to understand the neural underpinnings of expectation of incipient taste stimuli. Expectation plays an important role in the perception of food and in its evaluation (Deliza and MacFie 1996; Hurling and Shepherd 2003; Small 2008); 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).