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Food palatability and hedonic value play central roles in nutrient intake. However, postingestive effects can influence food preferences independently of palatability, although the neurobiological bases of such mechanisms remain poorly understood. Of central interest is whether the same brain reward circuitry that is responsive to palatable rewards also encodes metabolic value independently of taste signaling. Here we show that trpm5-/- mice, which lack the cellular machinery required for sweet taste transduction, can develop a robust preference for sucrose solutions based solely on caloric content. Sucrose intake induced dopamine release in the ventral striatum of these sweet-blind mice, a pattern usually associated with receipt of palatable rewards. Furthermore, single neurons in this same ventral striatal region showed increased sensitivity to caloric intake even in the absence of gustatory inputs. Our findings suggest that calorie-rich nutrients can directly influence brain reward circuits that control food intake independently of palatability or functional taste transduction.

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The motivation to start or terminate a meal involves the continual updating of information on current body status by central gustatory and reward systems. Previous electrophysiological and neuroimaging investigations revealed region-specific decreases in activity as the subject's state transitions from hunger to satiety. By implanting bundles of microelectrodes in the lateral hypothalamus, orbitofrontal cortex, insular cortex, and amygdala of hungry rats that voluntarily eat to satiety, we have measured the behavior of neuronal populations through the different phases of a complete feeding cycle (hunger-satiety-hunger). Our data show that while most satiety-sensitive units preferentially responded to a unique hunger phase within a cycle, neuronal populations integrated single-unit information in order to reflect the animal's motivational state across the entire cycle, with higher activity levels during the hunger phases. This distributed population code might constitute a neural mechanism underlying meal initiation under different metabolic states.

The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5 ؊/؊ mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products. chorda tympani ͉ gustatory cortex ͉ neurophysiology ͉ preference ͉ discrimination

Summary Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD.Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed.Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time.Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.

Consumption of calorie-containing sugars elicits appetitive behavioral responses and dopamine release in the ventral striatum, even in the absence of sweet-taste transduction machinery. However, it is unclear if such reward-related postingestive effects reflect preabsorptive or postabsorptive events. In support of the importance of postabsorptive glucose detection, we found that, in rat behavioral tests, high concentration glucose solutions administered in the jugular vein were sufficient to condition a side-bias. Additionally, a lower concentration glucose solution conditioned robust behavioral responses when administered in the hepatic-portal, but not the jugular vein. Furthermore, enteric administration of glucose at a concentration that is sufficient to elicit behavioral conditioning resulted in a glycemic profile similar to that observed after administration of the low concentration glucose solution in the hepatic-portal, but not jugular vein. Finally using fast-scan cyclic voltammetry we found that, in accordance with behavioral findings, a low concentration glucose solution caused an increase in spontaneous dopamine release events in the nucleus accumbens shell when administered in the hepatic-portal, but not the jugular vein. These findings demonstrate that the postabsorptive effects of glucose are sufficient for the postingestive behavioral and dopaminergic reward-related responses that result from sugar consumption. Furthermore, glycemia levels in the hepatic-portal venous system contribute more significantly for this effect than systemic glycemia, arguing for the participation of an intra-abdominal visceral sensor for glucose.