The neuronal logic of how internal states control food choice

A given stimulus can induce a pleasant or unpleasant sensation depending on the subject's internal state. The word alliesthesia is proposed to describe this phenomenon. It is, in itself, an adequate motivation for behavior such as food intake or thermoregulation. Therefore, negative regulatory feedback systems, based upon oropharingeal or cutaneous thermal signals are peripheral only in appearance, since the motivational component of the sensation is of internal origin. The internal signals seem to be complex and related to the set points of some regulated variables of the "milieu interieur," like set internal temperature in the case of thermal sensation (15). Alliesthesia can therefore explain the adaptation of these behaviors to their goals. Only three sensations have been studied- thermal, gustatory, and olfactory, but it is probable that alliesthesia also exists in such simple ways as in bringing a signal, usually ignored, to the subject's attention. For example, gastric contractions, not normally perceived, are felt in the state of hunger (16). Since alliesthesia relies on an internal input, it is possible that alliesthesia exists only with sensations related to some constants of the "milieu interieur" and therefore would not exist in visual or auditory sensations. As a matter of fact, luminous or auditory stimuli can be pleasing or displeasing in themselves, but there seems to be little variation of pleasure in these sensations, that is, no alliesthesia. There may be some esthetic value linked to these stimuli but it is a striking coincidence that they are in themselves rather neutral and that it is difficult to imagine a constant of the "milieu interieur" which could be possibly modified by a visual or an auditive stimulus-such as light of a certain wavelength or sound of a given frequency. In the light of this theory, it is possible to reconsider the nature of the whole conscious experience. The existence of alliesthesia implies the presence of internal signals modifying the concious sensations aroused from peripheral receptors. It is therefore necessary to question the existence of sensations aroused by direct stimulation of central receptors, such as hypothalamic temperature detectors, osmoreceptors, and others. Does their excitation arouse sensations of their own, or does the sensation have to pass through peripheral senses? Only human experimentation could answer this question. In the same way, it is possible that selfstimulation of the brain is pleasant, not by giving a sensation in itself, but because the electrical stimulus (17), renders peripheral stimuli pleasant.

The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. Copyright © 2014 Elsevier Inc. All rights reserved.

SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information.