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，大脑对感觉刺激的处理方式不同。在麻醉的动物中，没有内部的认知活动影响大脑，因此刺激是被动地接收和编码的，仅仅是为了它们的物理特性。另一方面，在清醒的受试者中，对刺激的反应受到正在进行的心理过程（即注意力，期望）的严重调制。同样的刺激，例如，根据动物的期望，会有不同的解释：例如，人类--和他们的大脑--被引导去期望一种温和的味道，可能会被“愚弄”，认为苦味比实际上要温和。 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反应的程度。味觉刺激的内在奖励/厌恶性质和食物选择对动物生存的重要性使得味觉成为直接研究期望在神经和行为水平上的影响的理想感觉系统。 拟进行的实验将在清醒的大鼠中进行;单个神经元的集合将被植入已知涉及味觉和期望的连接区域（GC、眶额皮质[OFC]、基底外侧杏仁核[BLA]）中的多个电极记录。期望的两个不同方面将被调查：一个未知的刺激（有点类似于注意的过程）和特定的期望一个已知的刺激的一般性期望。首先，老鼠将被训练通过按压杠杆来响应音调来收集味道。在这个范例中，音调不会提供任何关于味道身份的信息-它只会引发与未知刺激预期相关的注意力转移。另一方面，对特定刺激的期望将在另一个实验子集中得到解决，该实验涉及使用两种音调，每种音调都与按下杠杆时不同口味的可用性有关。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。两个行为任务将被用来研究特定期望的不同方面：第一个任务，去/不去，其中一个音调提示可口的味道（蔗糖或氯化钠）的可用性和其他的惩罚（奎宁）在按下杠杆，将揭示具有相反的情感价值的特定口味的期望的影响。第二个任务是双音调、双杠杆任务，其中每个音调与特定杠杆处可用的味道相关联，依赖于具有相似适口性的味道。这项任务将专门解决具有相似的情感价值，但不同的化学身份的刺激的期望的影响。自发活动，对预期线索的反应，以及对意想不到和预期的味道的反应将被记录在GC，OFC和BLA中，以解析一般和特定期望对味觉加工的影响。最后，将颅内插管植入OFC和BLA中，并将在上述实验条件下研究这两个区域在调节GC活性方面的贡献。 了解内部状态（如期望）对感觉反应的影响程度是感觉神经科学领域的一个核心问题。理解大脑如何对味觉的期望做出反应将揭示所有哺乳动物（包括人类）食物选择的复杂性，并将提供重要的信息，这些信息可能适用于肥胖和饮食失调的研究。

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.