Striatal Amplifiers of Incentive Salience.

Research into the neural circuits that underlie the amplification of motivation has been focused on the traditional “reward pathway.” Recent work, however, has implicated another striatal level structure, the central nucleus of the amygdala, in the amplification of motivation. Here, I extend these findings and demonstrate mu opioid receptor activation of the central nucleus of the amygdala enhances the motivational power of cues associated with reward. Recent findings in from human imaging studies have hinted that another striatal level structure, the neostriatum, may also participate in the amplification of motivation. Here, I demonstrate that mu opioid receptor activation in neostriatum enhances motivation for learned cues and primary rewards. Mu opioid receptor activation in dorsolateral neostriatum potently enhanced the attractiveness of cues in a manner similar to amygdala activation and did so in a manner not consistent with a habit hypothesis. However, consumption of primary rewards was not enhanced. Here, I demonstrated for the first time that enkephalin in dorsomedial neostriatum surges when rats consume a sweet, fatty food. Further, this consumption can be stimulated by microinjection of a mu opioid receptor activating drug. Although, dorsomedial neostriatal activation participated in motivation for primary rewards, activation did not have an effect on motivation for learned cues. Finally, in ventrolateral neostriatum, mu opioid receptor activation enhanced the attractiveness of a contiguous cue and motivation to consume primary rewards. These findings extend the neural substrates of motivation beyond traditional reward structures and have implications for the description and treatment of disorders of intense motivation such as drug addiction and binge eating.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99850/1/agdife_1.pd

Social, clinical, and policy implications of ultra-processed food addiction

Key messages Ultra-processed foods high in refined carbohydrates and added fats are highly rewarding, appealing, and consumed compulsively and may be addictive Behaviours around ultra-processed food may meet the criteria for diagnosis of substance use disorder in some people •   Ultra-processed food addiction is estimated to occur in 14% of adults and 12% of children and is associated with biopsychological mechanisms of addiction and clinically significant problems Understanding of these foods as addictive could lead to novel approaches in the realm of social justice, clinical care, and policy approache

Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions.

Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions

Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity

Prior work suggests that actual, but not estimated, energy density drives the reinforcing value of food and that energy from fat and carbohydrate can interact to potentiate reward. Here we sought to replicate these findings in an American sample and to determine if the effects are influenced by body mass index (BMI). Thirty participants with healthy weight (HW; BMI 21.92 ± 1.77; M ± SD) and 30 participants with overweight/obesity (OW/OB; BMI 29.42 ± 4.44) rated pictures of common American snacks in 120-kcal portions for liking, familiarity, frequency of consumption, expected satiety, healthiness, energy content, energy density, and price. Participants then completed an auction task where they bid for the opportunity to consume each food. Snacks contained either primarily carbohydrate, primarily fat, or roughly equal portions of fat and carbohydrate (combo). Replicating prior work, we found that participants with HW bid the most for combo foods in linear mixed model analyses. This effect was not observed among individuals with OW/OB. Additionally, in contrast with previous reports, our linear regression analyses revealed a negative relationship between the actual energy density of the snacks and bid amount that was mediated by food price. Our findings support altered macronutrient reinforcement in obesity and highlight potential influences of the food environment on the regulation of food reward

Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement

Published in final edited form as: Nat Neurosci. 2019 April ; 22(4): 586–597. doi:10.1038/s41593-019-0341-3.Striatal pavalbumin (PV) and cholinergic (CHI) interneurons are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells has made it difficult to directly assess their contribution to activity in networks of MSNs during behavior. Here, we build upon recent improvements in single cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntarily locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.Accepted manuscrip

Addiction

Background: There is growing evidence that an addictive-eating phenotype may exist. There is significant debate regarding whether highly processed foods (HPFs; foods with refined carbohydrates and/or added fats) are addictive. The lack of scientifically grounded criteria to evaluate the addictive nature of HPFs has hindered the resolution of this debate. Analysis: The most recent scientific debate regarding a substance’s addictive potential centered around tobacco. In 1988, the Surgeon General issued a report identifying tobacco products as addictive based on three primary scientific criteria: their ability to (1) cause highly controlled or compulsive use, (2) cause psychoactive (i.e. mood-altering) effects via their effect on the brain and (3) reinforce behavior. Scientific advances have now identified the ability of tobacco products to (4) trigger strong urges or craving as another important indicator of addictive potential. Here, we propose that these four criteria provide scientifically valid benchmarks that can be used to evaluate the addictiveness of HPFs. Then, we review the evidence regarding whether HPFs meet each criterion. Finally, we consider the implications of labeling HPFs as addictive. Conclusion: Highly processed foods (HPFs) can meet the criteria to be labeled as addictive substances using the standards set for tobacco products. The addictive potential of HPFs may be a key factor contributing to the high public health costs associated with a food environment dominated by cheap, accessible and heavily marketed HPFs.A.G. DiFeliceantonio is an iTHRIV Scholar. The iTHRIV Scholars Program is supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health, Grant/Award Numbers: UL1TR003015, KL2TR003016Published versio

Validity and reliability of a new whole room indirect calorimeter to assess metabolic response to small calorie loads

To provide an overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads.Seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events to assess WRIC validity. In a crossover design, 16 participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and carbohydrate oxidation. Bayesian Hierarchical Modeling was also used to model postprandial carbohydrate oxidation trajectories for each participant and condition.Mean total error in infusions were 1.270.67% and 0.420.70% for VO2 and VCO2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions (=1.050.03 kcal/min, p=0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p=0.29), postprandial carbohydrate oxidation parameters were significantly lower for dextrose compared with sucrose or fructose.Here, we provide evidence of validation of our WRIC and a novel application of statistical methods useful for research using WRIC.</p