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).