Effects of expectation on gustatory cortical activity

描述(申请人提供)：根据动物是清醒的还是麻醉的，大脑处理感官刺激的方式不同。在麻醉的动物中，内部认知活动不会影响大脑，因此刺激是被动地接收和编码的，完全是为了它们的物理特性。另一方面，在清醒的受试者中，对刺激的反应在很大程度上受到正在进行的心理过程(即注意力、期望)的调节。例如，根据动物的预期，同样的刺激会有不同的解释：例如，人类--以及他们的大脑--预期的是一种温和的味道，可能会被“愚弄”，认为苦味比实际味道要温和。本提案旨在研究这类现象的神经和系统基础：尤其是，这里概述的实验将解决预期影响大脑背景活动和对感觉刺激的反应的程度。味觉刺激的内在奖赏/厌恶性质以及食物选择对动物生存的重要性使味觉成为在神经和行为水平上直接研究预期影响的理想感觉系统。建议的实验将在清醒的大鼠身上进行；单个神经元的集合将被记录在连接的已知涉及味觉和期望的区域(GC，眶前叶皮质[OFC]，基底外侧杏仁核[BLA])中的多个电极。预期的两个不同方面将被研究：对未知刺激的一般性预期(这一过程有点类似于注意)和对已知刺激的特定预期。首先，老鼠将接受训练，通过按下杠杆对音调做出反应来收集味道。在这个范例中，音调不会提供任何关于味觉认同的信息--它只会触发与对未知刺激的预期有关的注意力转移。另一方面，对特定刺激的期望将在另一组实验中解决，这些实验涉及使用两种音调，每种音调都与按下杠杆时不同的味道有关。在这些实验中，听觉线索将提供有关预期特定味道的信息。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，一个进行/不进行，其中一个音调暗示是否有可口的味道(蔗糖或氯化钠)，另一个是按下杠杆的惩罚(奎宁)，将揭示对具有相反情感价值的特定味道的期望的影响。第二个任务是两个音调，两个杠杆任务，每个音调与特定水平上的味道相关联，依赖于具有相似可口性的味道。这项任务将专门解决期望对情感价值相似但化学特性不同的刺激的影响。GC、OFC和BLA将记录自发活动、对预期提示的反应以及对意外和预期口味的反应，以分析一般和特定预期对味觉加工的影响。最后，将颅内导管植入OFC和BLA，在上述实验条件下，将研究这两个区域在调节GC活性方面的贡献。理解预期等内部状态在多大程度上塑造感觉反应是感觉神经科学领域的一个中心问题。对大脑如何对口味做出反应的理解将有助于揭示所有哺乳动物--包括人类--选择食物的复杂性，并将提供重要信息，这些信息可能会应用于肥胖和饮食失调的研究。 与公共健康相关：这项建议旨在理解对初始味觉刺激的预期的神经基础。期望在对食物的感知和评价中起着重要作用(Deliza和Macfie，1996年；Hulling and Shepherd，2003；Small 2008)；因此，这一主题对与公共健康有关的问题，如食物喜好和选择，具有重要影响。此外，了解期望的神经基础对于研究安慰剂的神经机制是相关的(Nitschke等人。2006a；Nitschke等人。2006b；Sarinopoulos等人。2006)--对神经科学日益感兴趣的领域(Petrovic等人。2005年；Ploghaus等人。1999年)。

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).