Feeding is critical for survival and disruption in the mechanisms that govern food intake underlie disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation in rodent home-cages: The Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs.

A considerable amount of evidence shows that reactive oxygen species (ROS) in the mammalian brain are directly responsible for cell and tissue function and dysfunction. Excessive reactive oxygen species contribute to various conditions including inflammation, diabetes mellitus, neurodegenerative diseases, tumor formation, and mental disorders such as depression. Increased intracellular calcium levels have toxic roles leading to cell death. However, the exact connection between reactive oxygen production and high calcium stress is not yet fully understood. In this review, we focus on the role of reactive oxygen species and calcium stress in hypothalamic arcuate neurons controlling feeding. We revisit the role of NPY and POMC neurons in the regulation of appetite and energy homeostasis, and consider how ROS and intracellular calcium levels affect these neurons. These novel insights give a new direction to research on hypothalamic mechanisms regulating energy homeostasis and may offer novel treatment strategies for obesity and type-2 diabetes.

Abstract:A considerable amount of evidence shows that reactive oxygen species (ROS) in the mammalian brain are directly responsible for cell and tissue function and dysfunction. Excessive reactive oxygen species contribute to various conditions including inflammation, diabetes mellitus, neurodegenerative diseases, tumor formation, and mental disorders such as depression. Increased intracellular calcium levels have toxic roles leading to cell death. However, the exact connection between reactive oxygen production and high calcium stress is not yet fully understood. In this review, we focus on the role of reactive oxygen species and calcium stress in hypothalamic arcuate neurons controlling feeding. We revisit the role of NPY and POMC neurons in the regulation of appetite and energy homeostasis, and consider how ROS and intracellular calcium levels affect these neurons. These novel insights give a new direction to research on hypothalamic mechanisms regulating energy homeostasis and may offer novel treatment strategies for obesity and type-2 diabetes.

SummaryFeeding is critical for survival and disruption in the mechanisms that govern food intake underlie disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation: The Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs. In this paper we demonstrate the utility of FED3 in a range of experimental paradigms.In BriefUsing a novel, high-throughput home cage feeding platform, FED3, Matikainen-Ankney et al. quantify food intake and operant learning in groups of mice conducted at multiple institutions across the globe. Results include rates of operant efficiency, circadian feeding patterns, and operant optogenetic self-stimulation.HighlightsThe Feeding Experimentation Device version 3(FED3) records food intake and operant behavior in rodent home cages.Analysis of food intake includes total intake, meal pattern analysis, and circadian analysis of feeding patterns.FED3 also allows for operant behavioral assays to examine food learning and motivation.

This study investigated whether the PRL surge that precedes parturition is accompanied by a decrease in activity of hypothalamic tuberoinfundibular dopamine (TIDA) neurons, as occurs during the PRL surges of early pregnancy. Serial blood samples were collected at regular intervals during early and late pregnancy via chronic indwelling jugular cannulae, and concentrations of plasma PRL were determined by RIA. In addition, pregnant rats were killed at either 1200 and 0300 h on different days throughout pregnancy. Levels of TIDA neuronal activity were estimated using concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence as an index of dopamine metabolism. During early pregnancy, plasma PRL concentrations showed characteristic diurnal and nocturnal surges peaking at 1700 and 0300 h, respectively, whereas during late pregnancy, there was a broad nocturnal surge throughout the night preceding parturition. During early pregnancy, DOPAC was elevated at 1200 h, associated with suppressed plasma PRL, whereas at 0300 h, during the nocturnal PRL surge, DOPAC was significantly reduced (P < 0.05). On the last day of pregnancy DOPAC levels were significantly reduced at both 1200 and 0300 h compared with those at 1200 h in early pregnancy regardless of the PRL concentration. This experiment was repeated with additional groups to further characterize the timing of the fall in TIDA activity during late pregnancy. DOPAC concentrations were elevated throughout the second half of pregnancy, then fell significantly between 0300-1200 h on day 21, approximately 36 h before parturition. As in the previous experiment, the timing of changes in DOPAC concentrations in the median eminence was dissociated from the antepartum PRL surge. These data indicate that the regulation of PRL secretion during late pregnancy is different from that of early pregnancy. Despite the prolonged reduction in activity of TIDA neurons during late pregnancy, PRL secretion still occurs as a nocturnal surge, suggesting that dopamine is not the only regulator of PRL secretion at this time.