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Key points Obesity can disrupt the structure and function of organ systems, including the olfactory system that is important for food selection and satiety. We designed dietary treatments in mice such that mice received fat, but the total calories provided were the same as in control diets so that they would not gain weight or increase adipose tissue. Mice that were not obese but consumed isocaloric fatty diets still lost olfactory neuronal circuits, had fewer numbers of olfactory neurons, had an elevation in inflammatory signals, and an intermediate ability to clear glucose (prediabetes). Mice were allowed access to running wheels while consuming fatty diets, yet still lost olfactory structures. We conclude that a long-term imbalance in nutrition that favors fat in the diet disrupts the olfactory system of mice in the absence of obesity. Abstract Excess nutrition causes loss of olfactory sensory neurons (OSNs) and reduces odor discrimination and odor perception in mice. To separate diet-induced obesity from the consumption of dietary fat, we designed pair-feeding experiments whereby mice were maintained on isocaloric diets for 5 months that prevented increased fat storage. To test our hypothesis that adiposity was not a prerequisite for loss of OSNs and bulbar projections, we used male and female mice with an odorant receptor-linked genetic reporter (M72tauLacZ; Olfr160) to visualize neural circuitry changes resulting from fat in the diet. Simultaneously we monitored glucose clearance (diagnostic for prediabetes), body fat deposition, ingestive behaviors, select inflammatory markers, and energy metabolism. Axonal projections to defined olfactory glomeruli were visualized in whole-mount brains and the number of OSNs were manually counted across whole olfactory epithelia. After being pair fed a moderately high-fat (MHF) diet, mice of both sexes had body weight, adipose deposits, energy expenditure, respiratory exchange ratios, and locomotor activity that were unchanged from control-fed mice. Despite this, they were still found to lose OSNs and associated bulbar projections. Even with unchanged adipocyte storage, pair-fed animals had an elevation in TNF cytokines and an intermediate ability for glucose clearance. Albeit improving health metrics, access to voluntary running while consuming an ad libitum fatty diet, still precipitated a loss of OSNs and associated axonal projections for male mice. Our results support that long-term macronutrient imbalance can drive anatomical loss in the olfactory system regardless of total energy expenditure. This article is protected by copyright. All rights reserved.

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp’s ability to reduce food intake and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacological dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food intake and water intake. Blockade of Gpr160 in the 4V, independent of pharmacological CART treatment, caused an increase in both overnight food intake and water intake. The decrease in food intake, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a glucagon-like peptide 1 (GLP-1) receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and nonneuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection and extend these findings to water drinking. Gpr160ir was observed in both neuronal and nonneuronal cell types in regions known to be important in the multiple pharmacological effects of CARTp, identifying those areas as targets for future compromise of function studies.

Alcoholism and high fat diet (HFD)-induced obesity individually promote insulin resistance and glucose intolerance in clinical populations, increasing risk for metabolic diseases. HFD can also stimulate alcohol intake in short-term clinical studies. Unfortunately, there is currently a disconnect between animal models and the clinical findings, as animal studies typically show that HFD decreases ethanol intake while ethanol intake mitigates HFD-induced effects on insulin and glucose dysfunction. However, most previous animal studies utilized forced or continuous HFD and/or ethanol. In three experiments we sought to determine whether HFD (HFD = 60% calories from fat) vs. control diet (chow = 16% fat) alters voluntary two-bottle choice ethanol intake in male C57Bl/6J mice given differing access schedules for 6–7 weeks, and we assessed the resultant impact on metabolic function via insulin and glucose tolerance tests. Experiment 1: Unlimited Access Ethanol + HFD (UAE + HFD; n = 15; 10% ethanol v/v, ad libitum diet and ethanol) or UAE + Chow (n = 15). Experiment 2: Limited Access Ethanol + HFD (LAE + HFD; n = 15; ethanol = 4 h/day; 3 days/week, ad libitum diet) or LAE + Chow (n = 15) with increasing ethanol concentrations (10%, 15%, 20%). Experiment 3: Intermittent HFD with limited access to ethanol (iHFD-E; HFD = single 24-h session/week; ethanol = 4 h/day; 4 days/week) (n = 10). UAE + HFD mice consumed significantly less ethanol and were insulin-resistant and hyperglycemic compared with UAE + Chow mice. LAE + HFD mice consumed ethanol similarly to LAE + Chow mice, but exhibited hyperglycemia, insulin resistance, and glucose intolerance. iHFD-E mice displayed binge eating-like behaviors and consumed significantly more ethanol than mice given ad libitum chow or HFD. iHFD-E mice did not have significantly altered body composition, but developed insulin insensitivity and glucose intolerance. These findings suggest that access schedules influence HFD effects on ethanol consumption and resultant metabolic dysfunction, ethanol intake does not improve HFD-induced metabolic dysfunction, and binge eating-like behaviors can transfer to binge drinking behaviors.

There are examples of physiological conditions under which thirst is inappropriately exaggerated, and the mechanisms for these paradoxical ingestive behaviors remain unknown. We are interested in thirst mechanisms across the female life cycle and have identified a novel mechanism through which ingestive behavior may be activated. We discovered a previously unrecognized endogenous hypothalamic peptide, phoenixin (PNX), identified physiologically relevant actions of the peptide in brain and pituitary gland to control reproductive hormone secretion in female rodents, and in the process identified the previously orphaned G protein-coupled receptor Gpr173 to be a potential receptor for the peptide. Labeled PNX binding distribution in brain parallels areas known to be important in ingestive behaviors as well in areas where gonadal steroids feedback to control estrous cyclicity (Stein LM, Tullock CW, Mathews SK, Garcia-Galiano D, Elias CF, Samson WK, Yosten GLC, Am J Physiol Regul Integr Comp Physiol 311: R489–R496, 2016). We have demonstrated upregulation of Gpr173 during puberty, fluctuations across the estrous cycle, and, importantly, upregulation during the last third of gestation. It is during this hypervolemic, hyponatremic state that both vasopressin secretion and thirst are inappropriately elevated in humans. Here, we show that central administration of PNX stimulated water drinking in both males and females under ad libitum conditions, increased water drinking after overnight fluid deprivation, and increased both water and 1.5% NaCl ingestion under fed and hydrated conditions. Importantly, losartan pretreatment blocked the effect of PNX on water drinking, and knockdown of Gpr173 by use of short interfering RNA constructs significantly attenuated water drinking in response to overnight fluid deprivation. These actions, together with the stimulatory action of PNX on vasopressin secretion, suggest that this recently discovered neuropeptide may impact the recruitment of critically important neural circuits through which ingestive behaviors and endocrine mechanisms that maintain fluid and electrolyte homeostasis are regulated.

C1q/TNF-related protein (CTRP) family comprises fifteen highly conserved secretory proteins with diverse central and peripheral functions. In zebrafish, mouse, and human, CTRP4 is most highly expressed in the brain. We previously showed that CTRP4 is a metabolically responsive regulator of food intake and energy balance, and mice lacking CTRP4 exhibit sexually dimorphic changes in ingestive behaviors and systemic metabolism. Recent single-cell RNA sequencing also revealed Ctrp4/C1qtnf4 expression in diverse neuronal cell types across distinct anatomical brain regions, hinting at additional roles in the central nervous system not previously characterized. To uncover additional central functions of CTRP4, we subjected Ctrp4 knockout (KO) mice to a battery of behavioral tests. Relative to wild-type (WT) littermates, loss of CTRP4 does not alter exploratory, anxiety-, or depressive-like behaviors, motor function and balance, sensorimotor gating, novel object recognition, and spatial memory. While pain-sensing mechanisms in response to thermal stress and mild shock are intact, both male and female Ctrp4 KO mice have increased sensitivity to pain induced by higher-level shock, suggesting altered nociceptive function. Importantly, CTRP4 deficiency impairs hippocampal-dependent associative learning and memory as assessed by trace fear conditioning paradigm. This deficit is sex-dependent, affects only female mice, and is associated with altered expression of learning and memory genes (Arc, c-fos, and Pde4d) in the hippocampus and cortex. Altogether, our behavioral and gene expression analyses have uncovered novel aspects of the CTRP4 function and provided a physiological context to further investigate its mechanism of action in the central and peripheral nervous system.

The parabrachial nucleus (PBN) has long been recognized as a sensory relay receiving an array of interoceptive and exteroceptive inputs relevant to taste and ingestive behavior, pain, and multiple aspects of autonomic control, including respiration, blood pressure, water balance, and thermoregulation. Outputs are known to be similarly widespread and complex. How sensory information is handled in PBN and used to inform different outputs to maintain homeostasis and promote survival is only now being elucidated. With a focus on taste and ingestive behaviors, pain, and thermoregulation, this review is intended to provide a context for analysis of PBN circuits involved in aversion and avoidance, and consider how information of various modalities, interoceptive and exteroceptive, is processed within PBN and transmitted to distinct targets to signal challenge, and to engage appropriate behavioral and physiological responses to maintain homeostasis.

Impulsivity and compulsivity are multidimensional constructs that are increasingly considered determinants of obesity. Studies using functional magnetic resonance imaging (fMRI) have provided insight on how differences in brain response during tasks exploring facets of impulsivity and compulsivity relate to the ingestive behaviors that support the etiology and maintenance of obesity. In this narrative review, we provide an overview of neuroimaging studies exploring impulsivity and compulsivity factors as they relate to weight status. Special focus will be placed on studies examining the impulsivity-related dimensions of attentional bias, delayed gratification and emotion regulation. Discussions of compulsivity within the context of obesity will be restricted to fMRI studies investigating habit formation and response flexibility under shifting contingencies. Further, we will highlight neuroimaging research demonstrating how alterations in neuroendocrine functioning are linked to excessive food intake and may serve as a driver of the impulsive and compulsive behaviors observed in obesity. Research on the associations between brain response with neuroendocrine factors, such as insulin, peptide YY (PYY), leptin, ghrelin and glucagon-like peptide 1 (GLP-1), will be reviewed.

Genetic background of experimental animals contributes mainly to the variations in the experimental outcomes. Therefore, quails of two lines of plumage color (brown and recessive white) were studied to investigate the impact of plumage color mutations on the morphological structures of the oropharyngeal roof and also on the ingestive behavior and quail performance. Feeding intake and feed conversion ratio were higher in the brown quails, associated with nonsignificant increase of the live body weight and body weight gain. In the recessive white quails, ingestive behaviors revealed significant declines. The roof of the oropharynx roof was significantly longer in the recessive white quails; however, the upper beak was significantly longer and narrower in the brown ones. The length of the palate and pharynx showed nonsignificant increase in the recessive white quails. The median palatine ridge was formed of rostral continuous and caudal interrupted parts, and the lengths of these parts were slightly higher in the recessive white quails, meanwhile the lateral palatine ridge length showed a slight increase in the brown birds. Openings of intraepithelial glands were more numerous in the recessive white quails. The brown quails demonstrated more detectable and larger caudally directed conical shaped palatine and pharyngeal papillae, in addition to more considerable palatine salivary glands openings. The infundibular cleft was significantly wider in the recessive white quails, where its edges were characterized by lack of the pharyngeal papillae. The findings of this study will be beneficial for the breeders during selection the suitable quail lines for meat production purposes.

The existence of the peptide encoded by the cocaine- and amphetamine-regulated transcript (Cartpt) has been recognized since 1981, but it was not until 1995, that the gene encoding CART peptide (CART) was identified. With the availability of the predicted protein sequence of CART investigators were able to identify sites of peptide localization, which then led to numerous approaches attempting to clarify CART's multiple pharmacologic effects and even provide evidence of potential physiologic relevance. Although not without controversy, a picture emerged of the importance of CART in ingestive behaviors, reward behaviors and even pain sensation. Despite the wealth of data hinting at the significance of CART, in the absence of an identified receptor, the full potential for this peptide or its analogs to be developed into therapeutic agents remained unrealized. There was evidence favoring the action of CART via a G protein-coupled receptor (GPCR), but despite multiple attempts the identity of that receptor eluded investigators until recently. Now with the identification of the previously orphaned GPCR, GPR160, as a receptor for CART, focus on this pluripotent neuropeptide will in all likelihood experience a renaissance and the potential for the development of pharmcotherapies targeting GPR160 seems within reach.

Ghrelin is a major appetite-stimulating neuropeptide found in circulation. While its role in increasing food intake is well known, its role in affecting taste perception, if any, remains unclear. In this study, we investigated the role of the growth hormone secretagogue receptor’s (GHS-R, a ghrelin receptor) activity in the peripheral taste system using feeding studies and conditioned taste aversion assays by comparing wild-type and GHS-R-knockout models. Using transgenic mice expressing enhanced green fluorescent protein (GFP), we demonstrated GHS-R expression in the taste system in relation phospholipase C ß2 isotype (PLCβ2, type II taste cell marker)- and glutamate decarboxylase type 67 (GAD67, type III taste cell marker)-expressing cells using immunohistochemistry. We observed high levels of co-localization between PLCβ2 and GHS-R within the taste system, while GHS-R rarely co-localized in GAD67-expressing cells. Additionally, following 6 weeks of 60% high-fat diet, female Ghsr−/− mice exhibited reduced responsiveness to linoleic acid (LA) compared to their wild-type (WT) counterparts, while no such differences were observed in male Ghsr−/− and WT mice. Overall, our results are consistent with the interpretation that ghrelin in the taste system is involved in the complex sensing and recognition of fat compounds. Ghrelin-GHS-R signaling may play a critical role in the recognition of fatty acids in female mice, and this differential regulation may contribute to their distinct ingestive behaviors.

Taste sensitivity and liking drive food choices and ingestive behaviors from childhood to adulthood, yet their longitudinal association with dietary intake and BMI is largely understudied. Here, we examined the longitudinal relationship between sugar and fat sensitivity, sugar and fat liking, habitual dietary intake, and BMI percentiles in a sample of 105 healthy-weight adolescents (baseline: BMI %tile 57.0 ± 24.3; age 14–16 years) over a 4-year period. Taste sensitivity was assessed via a triangle fat and sweet taste discrimination test. Taste liking were rated on a visual analog scale for four milkshakes that varied in sugar and fat contents (high-fat/high-sugar (HF/HS), low-fat/high-sugar (LF/HS), high-fat/low-sugar (HF/LS), low-fat/low-sugar (LF/LS) milkshakes). A modified version of the reduced Block Food Frequency Questionnaire (BFFQ) was used to assess dietary intake. All measurements were repeated annually. Repeated measures correlations and linear mixed effects models were used to model the associations between the variables. Sugar sensitivity was negatively associated with liking for the LF/HS milkshake over the 4-year period. Low sugar sensitivity at baseline predicted increases in BMI percentile over time, but this association didn’t survive a correction for multiple comparisons. Percent daily intake from fat was positively associated with liking for the HF/HS milkshake and negatively associated with liking for the LF/LS milkshake over 4 years. Together, these results demonstrate that lower sensitivity to sweet taste is linked to increased hedonic response to high-sugar foods and increased energy intake from fat seems to condition adolescents to show increased liking for high-fat/high-sugar foods.

Measurement of drinking behavior in laboratory animals is an often utilized method in many areas of scientific research, including the study of ingestive behaviors and addictions. We have designed a system that measures drinking by continuously tracking fluid-filled bottle weights with load cells and calculating change in fluid weight per drinking bout. The load cells serve both as a contact sensor that detects mouse-spout contact, as well as a monitor of fluid weight change per contact bout. The design described here fulfills several key criteria, including automated and continuous recording of drinking in the home-cage, automated control of liquid access, and inexpensive/reproducible fabrication. These features may allow researchers to generate high-resolution, detailed information on drinking behavior in high-throughput experimental designs. Here, we provide an overview of the design and present results from tests to validate the system. C57BL/6J mice were offered water and ethanol concurrently, using this system. Consumption weights were determined by the system and independently by conventional approaches. The results indicated a near-perfect correlation between the two methods, indicating the system returned valid consumption weights. This system functions as a valid drinking monitor that provides temporally precise data with a low cost design.

Functional neuroimaging studies in obesity have identified alterations in the connectivity within the reward network leading to decreased homeostatic control of ingestive behavior. However, the neural mechanisms underlying sex differences in the prevalence of food addiction in obesity is unknown. The aim of the study was to identify functional connectivity alterations associated with: (1) Food addiction, (2) Sex- differences in food addiction, (3) Ingestive behaviors. 150 participants (females: N = 103, males: N = 47; food addiction: N = 40, no food addiction: N = 110) with high BMI ≥ 25 kg/m2 underwent functional resting state MRIs. Participants were administered the Yale Food Addiction Scale (YFAS), to determine diagnostic criteria for food addiction (YFAS Symptom Count ≥ 3 with clinically significant impairment or distress), and completed ingestive behavior questionnaires. Connectivity differences were analyzed using a general linear model in the CONN Toolbox and images were segmented using the Schaefer 400, Harvard–Oxford Subcortical, and Ascending Arousal Network atlases. Significant connectivities and clinical variables were correlated. Statistical significance was corrected for multiple comparisons at q

The biomechanical and adaptive significance of variation in craniodental and mandibular morphology in fossil hominins is not always clear, at least in part because of a poor understanding of how different feeding behaviors impact feeding system design (form–function relationships). While laboratory studies suggest that ingestive behaviors produce variable loading, stress, and strain regimes in the cranium and mandible, understanding the relative importance of these behaviors for feeding system design requires data on their use in wild populations. Here we assess the frequencies and durations of manual, ingestive, and masticatory behaviors from more than 1400 observations of feeding behaviors video-recorded in a wild population of bearded capuchins (Sapajus libidinosus) at Fazenda Boa Vista in Piauí, Brazil. Our results suggest that ingestive behaviors in wild Sapajus libidinosus were used for a range of food material properties and typically performed using the anterior dentition. Coupled with previous laboratory work indicating that ingestive behaviors are associated with higher mandibular strain magnitudes than mastication, these results suggest that ingestive behaviors may play an important role in craniodental and mandibular design in capuchins and may be reflected in robust adaptations in fossil hominins.

Objective:To characterize the prevalence of hyperpalatable foods (HPF) among baby foods in the U.S. and examine the prevalence of HPF exposure and consumption from both baby food and adult food sources among infants aged 9–15 months.Methods:A U.S. baby food database as well as baby foods from three 24-h dietary recalls of 147 infants were used to identify baby foods as HPF per previous publication. HPF exposure was defined as intake of any HPF during the 3-day measurement period. To determine the extent of HFP consumption, % kilocalorie (kcal) intake from HPF was characterized.Results:Only 12% of baby foods were HPF; however, nearly all participants (>90%) consumed HPF, primarily through exposure to adult foods. Younger infants (Conclusions:The prevalence of HPF among baby foods in the U.S. is low. However, almost all infants were exposed to HPF, and HPF comprised a substantial percentage of daily food kilocalorie in infants' diets. Findings highlight the transition to solid food consumption during complimentary feeding period is a critical time for early HPF exposure.

Activation of membrane-associated estrogen receptors (mER) decreases food and water intake in female rats. Additional studies suggest these effects are mediated, at least in part, by membrane-associated estrogen receptor alpha (ERα). Nevertheless, the critical site of action and the intracellular signaling required for the ingestive effects of ERα remain unclear. Estradiol given to the medial preoptic area (mPOA) decreases ingestive behaviors, and membrane-associated ERα has been shown to affect intracellular signaling through interactions with metabotropic glutamate receptor (mGluR) subtypes, but an involvement of this signaling pathway, in the mPOA, in ingestive behavior remains untested. To address these open questions, we first showed that activation of mER in the mPOA decreased both overnight food and water intake, and did so in a time course consistent with a genomic mechanism of action. Next, we tested the requirement of mGluR1a signaling in the mPOA for the anorexigenic and anti-dipsogenic effects of estradiol. As expected, estradiol in the mPOA decreased food intake, but only in the absence of an mGluR1a antagonist. The same was not true for estradiol effects on water intake, which were unaffected by an mGluR1a antagonist. These results suggest that estrogens require mGluR activation for at least some of their effects on ingestive behaviors, and indicate that the mPOA is a critical site of action. The results also reveal an interesting divergence in the estrogenic control of ingestive behavior by which mGluR signaling in the mPOA plays a role in the control of food intake, but not water intake.

Common dietary fatty acids, including palmitic acid, stearic acid, oleic acid, and polyunsaturated fatty acids, have been studied in the context of overall dietary fat and shown to impact on several types of behaviors, most prominently cognitive behaviors and ingestive behaviors. The independent effects of these fatty acids have been less well-delineated. Several studies implicate these common fatty acids in modulation of the CNS immune/inflammatory response as a key mediator of behavioral effects. However, signaling actions of the fatty acids to regulate cell structure and neuronal or synaptic function have been identified in numerous studies, and the relevance or contribution(s) of these to ingestive behavioral outcomes represent an area for future study. Finally, fatty acids are precursors of endocannabinoids and their structural congeners. Being highly dynamic and complex, the endocannabinoid system plays a key role ingestive behavior via cellular and synaptic mechanisms, thus representing another important area for future study.

The employment of explosive weaponry in modern warfare exposes populations to shock wave-induced and impact-related brain injuries. Among the most common clinical complaints resulting from traumatic brain injury (TBI) are sleep-wake disturbances. The current study assessed the acute effects of mild concussive brain injury (CBI) and mild blast wave-induced brain injury (BTBI) on mouse behavior and orexin-A expression. Male C57BL/6J mice were exposed to CBI, BTBI, or sham procedures. Injured animals and their shams were further divided into the following subgroups: 24-h survival in standard group (SG) housing, 72-h survival in SG housing, and 72-h survival in Any-Maze cages (AMc). AMc enabled continuous monitoring of home cage activities. BTBI caused significant but transient decreases in wheel running and ingestive behaviors 24 h post-injury (PI), while CBI transiently decreased running and water intake. BTBI resulted in general hypoactivity in the open field (OF) at both PI time points for SG-housed animals. In contrast, CBI did not cause hypoactivity. Mice subjected to CBI traveled more in the center of the OF at both time points PI, suggesting that CBI caused reduced anxiety in mice. Increased activity in the center of the OF was also seen at 24 h PI after BTBI. CBI treatment caused increased CD11b immunostaining. However, neither injury was accompanied by an alteration in the number of orexin-A hypothalamic neurons. Taken together, shock wave exposure and concussive injury transiently reduced mouse activities, but some differences between the two injuries were seen.

Arcuate hypothalamus-derived agouti-related protein (AgRP) and neuropeptide Y (NPY) are critical for maintaining energy homeostasis. Fasting markedly upregulates AgRP/NPY expression and circulating ghrelin, and exogenous ghrelin treatment robustly increases acute food foraging and food intake, and chronic food hoarding behaviors in Siberian hamsters. We previously demonstrated that 3rd ventricular AgRP injection robustly stimulates acute and chronic food hoarding, largely independent of food foraging and intake. By contrast, 3rd ventricular NPY injection increases food foraging, food intake, and food hoarding, but this effect is transient and gone by 24 h post-injection. Because of this discrepancy in AgRP/NPY-induced ingestive behaviors, we tested whether selective knockdown of AgRP blocks fasting and ghrelin-induced increases in food hoarding. AgRP gene knockdown by a novel DICER small interfering RNA (AgRP-DsiRNA) blocked food-deprivation induced increases in AgRP expression, but had no effect on NPY expression. AgRP-DsiRNA attenuated acute (1 day), and significantly decreased chronic (4-6 days), food deprivation-induced increases in food hoarding. In addition, AgRP-DsiRNA treatment blocked exogenous ghrelin-induced increases in food hoarding through day 3, but had no effect on basal food foraging, food intake, or food hoarding prior to ghrelin treatment. Lastly, chronic AgRP knockdown had no effect on body mass, fat mass, or lean mass in either food deprived or ad libitum fed hamsters. These data collectively suggest that the prolonged increase in food hoarding behavior following energetic challenges, and food deprivation especially, is primarily regulated by downstream AgRP signaling.

Objectives Taste disorders are relatively common, but it is unknown whether taste variations are related to ingestive behaviors and general health. We used genetic manipulation of functional chemosensory receptor neurons in the model organism Drosophila melanogaster (fruit fly) to determine how NaCl taste disorder leads to various changes in its behavior and lifespan. Materials and methods Two types of flies with peripheral taste deficiency were prepared and analyzed: 1) Gr5a-rpr transgenic flies, which have partially defective receptor neurons that undergo apoptosis, and 2) ΔXbs6 flies, a homeotic Pox neuro mutant that exhibits specific ablation of external taste organs, including most taste neurons, with other organs remaining intact. These flies were compared with wild-type control flies ( w 1118 ) in terms of feeding and breeding (egg-laying) behaviors, both controlled by inputs from salt-sensitive taste neurons. Results Control and Gr5a-rpr flies consumed NaCl in a dose-dependent manner, peaking at 80 mM. The ΔXbs6 flies showed significantly decreased consumption in both sexes. NaCl-based selection of egg-laying sites was almost absent in ΔXbs6 females until the fourth day after emergence, with partial inhibition thereafter. However, there was no difference in lifespan between ΔXbs6 and control flies. Conclusions The results of this study suggest that although NaCl taste disorder results in reduced feeding and breeding behaviors in Drosophila , it does not impact lifespan.

The RumiWatch System (Itin+Hoch GmbH, Liestal, Switzerland) is a sensor system that enables quantification of ingestive behaviors of cattle that may be useful, amongst other things, for estimating dry matter intake. There are currently multiple versions of the RumiWatch Converter software used to convert the recorded data into specific animal behaviors through the use of algorithms. The objective of this research was to evaluate the use of RumiWatch System noseband sensors for quantifying the number of prehension bites and mastication chews in grazing and stall-fed dairy cows using RumiWatch Converter software versions 0.7.3.36 (RWC36) and 0.7.4.13 (RWC13). Two experiments using lactating Holstein-Friesian dairy cattle were conducted. In Experiment I, ten cows grazed perennial ryegrass pasture (Lolium perenne L.) in individual plots that measured 35 m2, with a pasture mass of 2500 kg DM/ha and pasture allowance of 28 kg DM/d. In Experiment II, 14 cows were offered 16 kg DM/d of perennial ryegrass pasture silage in individual indoor feed stalls. In both experiments, ingestive behaviors were quantified with the jaw movement halters and through visual observation using video recordings. The performance of the RumiWatch Converter software was evaluated through Lin’s concordance correlation coefficients with video observation. For grazing cows, there was greater concordance between the RumiWatch System and video observation for the number of prehension bites (0.94 for RWC36 and 0.75 for RWC13) than for the number of mastication chews (0.20 for RWC36 and 0.14 for RWC13). In cows fed in stalls, there was also greater concordance for the number of prehension bites (0.54 for RWC36 and 0.64 for RWC13) than for the number of mastication chews (0.46 for RWC36 and 0.58 for RWC13). However, the RWC36 was more accurate for quantifying feeding behaviors of grazing cows than the RWC13, while for stall fed cows the reverse was true. Overall, both RumiWatch Converters were better at quantifying prehension bites in grazing cows than in stall fed cows, but better at quantifying mastication chews in stall fed cows than grazing cows. These data enable a new understanding of the how these RumiWatch sensors should best be used for measuring cows' feeding behaviors in different feeding systems.

Determining ingestive behaviors of dairy cows is critical to evaluate their productivity and health status. The objectives of this research were to (1) develop the relationship between forage species/heights and sound characteristics of three different ingestive behaviors (bites, chews, and chew-bites), (2) comparatively evaluate three deep learning models and optimization strategies for classifying the three behaviors, and (3) examine the ability of deep learning modeling for classifying the three ingestive behaviors under various forage characteristics. The results show that the amplitude and duration of the bite, chew, and chew-bite sounds were mostly larger for tall forages (tall fescue and alfalfa) compared to their counterparts. The long short-term memory network using a filtered dataset with balanced duration and imbalanced audio files offered better performance than its counterparts. The best classification performance was over 0.93, and the best and poorest performance difference was 0.4–0.5 under different forage species and heights. In conclusion, the deep learning technique could classify the dairy cow ingestive behaviors but was unable to differentiate between them under some forage characteristics using acoustic signals. Thus, while the developed tool is useful to support precision dairy cow management, it requires further improvement.

Amylin is produced in the pancreas and the brain, and acts centrally to reduce feeding and body weight. Recent data show that amylin can act in the ventral tegmental area (VTA) to reduce palatable food intake and promote negative energy balance, but the behavioral mechanisms by which these effects occur are not fully understood. The ability of VTA amylin signaling to reduce intake of specific palatable macronutrients (fat or carbohydrate) was tested in rats in several paradigms, including one-bottle acceptance tests, two-bottle choice tests, and a free-choice diet. Data show that VTA amylin receptor activation with the amylin receptor agonist salmon calcitonin (sCT) preferentially and potently reduces intake of fat, with more variable suppression of sucrose intake. Intake of a non-nutritive sweetener is also decreased by intra-VTA administration of sCT. As several feeding-related signals that act in the mesolimbic system also impact motivated behaviors besides feeding, we tested the hypothesis that the suppressive effects of amylin signaling in the VTA extend to other motivationally relevant stimuli. Results show that intra-VTA sCT reduces water intake in response to central administration of the dipsogenic peptide angiotensin II, but has no effect on ad libitum water intake in the absence of food. Importantly, open field and social interaction studies show that VTA amylin signaling does not produce anxiety-like behaviors. Collectively, these findings reveal a novel ability of VTA amylin receptor activation to alter palatable macronutrient intake, and also demonstrate a broader role of VTA amylin signaling for the control of motivated ingestive behaviors beyond feeding.

In order to examine genetic influences on fluid ingestion, 20-min intake of either water or 0.1 M sucrose was measured in a lickometer in 18 isogenic strains of mice, including 15 inbred strains and 3 F1 hybrid crosses. Intake and licking data were examined at a number of levels, including lick rate as defined by mean or median interlick interval, as well as several microstructural parameters (i.e. burst-pause structure). In general, strain variation for ingestive phenotypes were correlated across water and sucrose in all strains, indicating fundamental, rather than stimulus-specific, mechanisms of intake. Strain variation was substantial and robust, with heritabilities for phenotypes ranging from 0.22 to 0.73. For mean interlick interval (MPI; a measure of lick rate) strains varied continuously from 94.3 to 127.0 ms, a range consistent with previous studies. Furthermore, variation among strains for microstructural traits such as burst size and number suggested that strains possess different overall ingestive strategies, with some favoring more short bursts, and others favoring fewer, long bursts. Strains also varied in cumulative intake functions, exhibiting both linear and decelerated rates of intake across the session.

There exists diversity among individuals in difficulty controlling body weight. Body weight control, or obesity prevention, requires cognitive control over ingestive behavior, which may account for the diverse ability of body weight control. The caudate nuclei, especially the dorsal area, have been shown to play critical roles in ingestive behaviors, which significantly influences body weight control. However, the practice of body weight control is dependent on the body weight status, because the current obesity status determines the need for body weight control. To elucidate the underlying neural mechanism that accounts for individual differences in obesity prevention, we aimed to isolate functional caudate connectivity responsible for the underlying tendency of obesity prevention, independent of the current obesity status, using resting state fMRI data, body mass index (BMI), and assessment of ingestive behavior from 185 individuals from the NKI-Rockland sample. The underlying tendency of obesity prevention was estimated from BMI and behavioral and cognitive components of food intake. Functional connectivities between the caudate head and the whole brain were tested as a function of the estimated tendency in a voxel-wise manner. The bilateral precuneus showed inverse association between its connectivity to the caudate and the estimated tendency. Caudate-precuneus connectivity may have significant implications to understanding personal differences that accounts for the success in body weight control.

Objective This preliminary study explored whether differences in meal-stimulated insulin or amylin release are linked to altered ingestive behaviors in individuals with bulimia nervosa (BN) or purging disorder (PD). Method Women with BN (n = 15), PD (n = 16), or no eating disorder (n = 18) underwent structured clinical interviews and assessments of gut hormone and subjective responses to a fixed test meal. Multilevel model analyses were used to explore whether gut hormone responses contribute to subjective responses to the test meal and whether these associations differed by group. Results Insulin and amylin levels significantly increased following the test meal. Women with PD showed greater insulin release compared to those with BN, but not controls. Multilevel models support significant group X insulin interactions predicting subjective ratings of nausea and urge to vomit, with a stronger association between higher insulin responses and higher nausea and urge to vomit in women with PD and BN. Amylin responses did not differ by group. Conclusion Increased sensitivity to the effects of insulin on nausea and urge to vomit may be linked to purging in both PD and BN. Differences in postprandial insulin levels may be linked to purging behavior in the absence versus presence of binge eating.

Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including cardiovascular tone, pain processing, ingestive behaviors, locomotor drive, sleep, addiction and social behaviors. Yet, there is incomplete understanding about how the various populations of Nts neurons distributed throughout the brain mediate such physiology. This knowledge gap largely stemmed from the inability to simultaneously identify Nts cell bodies and manipulate them in vivo. One means of overcoming this obstacle is to study Nts(Cre) mice crossed onto a Cre-inducible green fluorescent reporter line (Nts(Cre);GFP mice), as these mice permit both visualization and in vivo modulation of specific populations of Nts neurons (using Cre-inducible viral and genetic tools) to reveal their function. Here we provide a comprehensive characterization of the distribution and relative densities of the Nts-GFP populations observed throughout the male Nts(Cre);GFP mouse brain, which will pave the way for future work to define their physiologic roles. We also compared the distribution of Nts-GFP neurons with Nts-In situ Hybridization (Nts-ISH) data from the adult mouse brain. By comparing these data sets we can distinguish Nts-GFP populations that may only transiently express Nts during development but not in the mature brain, and hence which populations may not be amenable to Cre-mediated manipulation in adult Nts(Cre);GFP mice. This atlas of Nts-GFP neurons will facilitate future studies using the Nts(Cre);GFP line to describe the physiological functions of individual Nts populations and how modulating them may be useful to treat disease.

Central serotonin (5-HT) pathways are known to influence feeding and other ingestive behaviors. Although the ventral tegmentum is important for promoting the seeking and consumption of food and drugs of abuse, the roles of 5-HT receptor subtypes in this region on food intake have yet to be comprehensively examined. In these experiments, food restricted rats were given 2-hr access to rat chow; separate groups of non-restricted animals had similar access to a sweetened fat diet. Feeding and locomotor activity were monitored following ventral tegmentum stimulation or blockade of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, or 5-HT2C receptors. 5-HT1A receptor stimulation transiently inhibited rearing behavior and chow intake in food-restricted rats, and had a biphasic effect on non-restricted rats offered the palatable diet. 5-HT1B receptor agonism transiently inhibited feeding in restricted animals, but did not affect intake of non-restricted rats. In contrast, 5-HT1B receptor antagonism decreased palatable feeding. Although stimulation of ventral tegmental 5-HT2B receptors with BW723C86 did not affect hunger-driven food intake, it significantly affected palatable feeding, with a trend for an increasing intake at 2.0 μg/side but not at 5.0 μg/side. Antagonism of the same receptor modestly but significantly inhibited feeding of the palatable diet at 5.0 μg/side ketanserin. Neither stimulation nor blockade of 5-HT2A or 5-HT2C receptors caused prolonged effects on intake or locomotion. These data suggest that serotonin’s effects on feeding within the ventral tegmentum depend upon the specific receptor targeted, as well as whether intake is motivated by food restriction or the palatable nature of the offered diet.

Background Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to decrease ethanol (EtOH) drinking in rodent assays. The GLP-1 system also powerfully modulates food and fluid intake, gastrointestinal functions, and metabolism. To begin to understand the neurobiological mechanisms by which GLP-1 receptor ligands may be able to control EtOH intake, it is important to ascertain whether they can modulate the direct reinforcing effects of EtOH, without the confound of effects on ingestive behaviors generally. Methods We trained experimentally naive, free-fed C57BL/6J mice to self-administer EtOH intravenously. Once stable EtOH intake was acquired, we tested the effect of acute pretreatment with the GLP-1 receptor agonist Exendin-4. Effect of Exendin-4 on operant behavior reinforced by a palatable liquid food was similarly evaluated as a control. Results Intravenous EtOH functioned as a positive reinforcer in over half the mice tested. In mice that acquired self-administration, EtOH intake was high, indeed, reaching toxic doses; 3.2 μg/kg Exendin-4 decreased intravenous EtOH intake by at least 70%, but had no significant effect on food-maintained operant responding. Conclusions This experiment produced 2 main conclusions. First, although technically challenging and yielding only moderate throughput, the intravenous self-administration procedure in mice is feasible, and sensitive to pharmacological manipulations. Second, GLP-1 receptor agonists can powerfully attenuate voluntary EtOH intake by directly modulating the reinforcing effects of EtOH. These findings support the potential usefulness of GLP-1 receptor ligands in the treatment of alcohol use disorder.

Feeding is a highly complex behavior that is influenced by learned associations between external and internal cues. The type of excessive feeding behavior contributing to obesity onset and metabolic deficit may be based, in part, on conditioned appetitive and ingestive behaviors that occur in response to environmental and/or interoceptive cues associated with palatable food. Therefore, there is a critical need to understand the neurobiology underlying learned aspects of feeding behavior. The stomach-derived “hunger” hormone, ghrelin, stimulates appetite and food intake and may function as an important biological substrate linking mnemonic processes with feeding control. The current review highlights data supporting a role for ghrelin in mediating the cognitive and neurobiological mechanisms that underlie conditioned feeding behavior. We discuss the role of learning and memory on food intake control (with a particular focus on hippocampal-dependent memory processes) and provide an overview of conditioned cephalic endocrine responses. A neurobiological framework is provided through which conditioned cephalic ghrelin secretion signals in neurons in the hippocampus, which then engage orexigenic neural circuitry in the lateral hypothalamus to express learned feeding behavior.

The present study aimed to evaluate the effects of pharmacological manipulation of α-adrenergic agonists in the dorsal raphe nucleus (DR) on food intake in satiated rats. Adult male Wistar rats with chronically implanted cannula in the DR were injected with adrenaline (AD) or noradrenaline (NA) (both at doses of 6, 20 and 60 nmol), or α-1 adrenergic agonist phenylephrine (PHE) or α-2 adrenergic agonist clonidine (CLO) (both at doses of 6 and 20 nmol). The injections were followed by the evaluation of ingestive behaviors. Food and water intake were evaluated for 60 min. Administration of AD and NA at 60 nmol and CLO at 20 nmol increased food intake and decreased latency to start consumption in satiated rats. The ingestive behavior was not significantly affected by PHE treatment in the DR. CLO treatment increased Fos expression in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) in rats that were allowed to eat during the experimental recording (AF group). However, when food was not offered during the experiment (WAF group), PVN neurons were not activated, whereas, neuronal activity remained high in the ARC when compared to control group. Noteworthy, ARC POMC neurons expressed Fos in the AF group. However, double-labeled POMC/Fos cells were absent in the ARC of the WAF group, although an increase in Fos expression was observed in non-POMC cells after CLO injections in the WAF group. In conclusion, the data from the present study highlight that the pharmacological activation of DR α-adrenoceptors affects food intake in satiated rats. The feeding response evoked by CLO injections into DR was similar to that induced by NA or AD injections, suggesting that the hyperphagia after NA or AD treatment depends on α-2 adrenoceptors activation. Finally, we have demonstrated that CLO injections into DR impact neuronal activity in the ARC, possibly evoking a homeostatic response toward food intake.

Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we highlight the effect of estrogens on food intake regulation and the latest literature on intracellular estrogen signaling. In addition, gut satiety hormones, such as cholecystokinin, glucagon-like peptide 1 and leptin are essential to regulate ingestive behaviors in the postprandial period. These peripheral signals are sensed by vagal afferent terminals in the gut wall and transmitted to the hindbrain axis. Here we 1. review the role of the vagus-hindbrain axis in response to gut satiety signals and 2. consider the potential synergistic effects of estrogens on gut satiety signals at the level of vagal afferent neurons and nuclei located in the hindbrain. Understanding the action of estrogens in gut-brain axis provides a potential strategy to develop estrogen-based therapies for metabolic diseases and emphasizes the importance of sex difference in the treatment of obesity.

RATIONALE: Whereas co-use of alcohol and marijuana is prevalent in adolescents, the effects of such drug co-exposure on ingestive and cognitive behaviors remain largely unexplored. We hypothesized that co-exposure to alcohol and Δ(9)-tetrahydrocannabinol (THC), the main psychoactive constitute of marijuana, alters feeding behavior and cognition differently from either drug alone. METHODS: Male rats received daily THC (3–20 mg/kg/day) or oil vehicle through subcutaneous injection or consumption of a cookie with access to saccharin or saccharin-sweetened alcohol during adolescence (P30–45). Barnes maze and sucrose preference tests were applied to assess spatial memory and behavioral flexibility and abstinence-related anhedonia, respectively. RESULTS: Subcutaneous THC did not affect alcohol intake, but dose-dependently increased acute (3-h) chow intake and reduced weight gain. Moderate alcohol consumption reduced the acute hyperphagic effect of subcutaneous THC. By contrast, oral THC at a dose > 5 mg/kg robustly reduced alcohol intake without affecting 3-h chow intake. At this dose, some rats stopped consuming the THC-laced cookies. Furthermore, oral THC reduced weight gain, and co-exposure to alcohol alleviated this effect. Chronic subcutaneous, but not oral, THC reduced sucrose intake during abstinence. Neither treatment impaired cognitive behaviors in the Barnes maze. CONCLUSION: Moderate alcohol and THC consumption can interact to elicit unique outcomes on ingestive behaviors and energy balance. Importantly, this study established a novel model of voluntary alcohol and THC consumption for studying mechanisms underlying the consequences of adolescent onset co-use of the two drugs.

The precise regulation of fluid and energy homeostasis is essential for survival. It is well appreciated that ingestive behaviors are tightly regulated by both peripheral sensory inputs and central appetite signals. With recent neurogenetic technologies, considerable progress has been made in our understanding of basic taste qualities, the molecular and/or cellular basis of taste sensing, and the central circuits for thirst and hunger. In this review, we first highlight the functional similarities and differences between mammalian and invertebrate taste processing. We then discuss how central thirst and hunger signals interact with peripheral sensory signals to regulate ingestive behaviors. We finally indicate some of the directions for future research.

This review is part of a special issue dedicated to Opioid addiction, and examines the influential role of opioid peptides, opioid receptors and opiate drugs in mediating food intake and body weight control in rodents. This review postulates that opioid mediation of food intake was an example of "positive addictive" properties that provide motivational drives to maintain opioid-seeking behavior and that are not subject to the "negative addictive" properties associated with tolerance, dependence and withdrawal. Data demonstrate that opiate and opioid peptide agonists stimulate food intake through homeostatic activation of sensory, metabolic and energy-related In contrast, general, and particularly mu-selective, opioid receptor antagonists typically block these homeostatically-driven ingestive behaviors. Intake of palatable and hedonic food stimuli is inhibited by general, and particularly mu-selective, opioid receptor antagonists. The selectivity of specific opioid agonists to elicit food intake was confirmed through the use of opioid receptor antagonists and molecular knockdown (antisense) techniques incapacitating specific exons of opioid receptor genes. Further extensive evidence demonstrated that homeostatic and hedonic ingestive situations correspondingly altered the levels and expression of opioid peptides and opioid receptors. Opioid mediation of food intake was controlled by a distributed brain network intimately related to both the appetitive-consummatory sites implicated in food intake as well as sites intimately involved in reward and reinforcement. This emergent system appears to sustain the "positive addictive" properties providing motivational drives to maintain opioid-seeking behavior.

During extracellular dehydration, neural systems that sense deficits in body fluid homeostasis operate in tandem with those that mediate motivation and reward in order to promote ingestive behaviors that restore fluid balance. We hypothesized that hypothalamic orexin (Ox) neurons act as an interface to couple brain regions sensing and processing information about body fluid status with central nervous system motivation and reward systems. An initial set of anterograde and retrograde tracing experiments suggested that structures along the lamina terminalis (LT), a region of the forebrain that serves to monitor and integrate information reflecting body fluid balance, project to hypothalamic Ox neurons that, in turn, project to dopamine neurons in the ventral tegmental area (VTA). A second set of experiments determined whether Ox neuron activation is associated with extracellular dehydration and the seeking out and consumption of water and saline. An elevation of Fos-like immunoreactivity in Ox neurons was observed in fluid-depleted rats that were allowed to ingest water and sodium. A final experiment was conducted to determine whether Ox release in the VTA promotes thirst and salt appetite. Bilateral microinjection of the Ox Type I receptor antagonist SB-408124 into the VTA prior to acute extracellular dehydration attenuated fluid intake. Together, these studies support the hypothesis that structures along the LT modulate activity in the VTA through actions of orexinergic neurons that have cell bodies in the hypothalamus. This pathway may function to facilitate sustained consumption of fluids necessary for restoration of fluid balance. (PsycINFO Database Record

Prokineticins are involved in many physiological processes including circadian rhythms, neurogenesis, angiogenesis, and cancer. Recently, they have been found to play a role in regulating food intake. Historically, proteins that increase feeding behavior in mammals decrease reproductive behavior to prevent pregnancy and lactation when food is scarce. In the current study, prokineticin-2 (PK2) had pronounced effects on reproductive and ingestive behaviors when given to female Syrian hamsters. Administration of PK2 prevented ingestive behaviors induced by food restriction, such as the amount of time spent with food and eating. Hamsters given PK2 preferred to engage in reproductive behaviors, including spending time with a male and lordosis. Furthermore, analysis of blood plasma revealed that changes to behavior persisted despite similar levels of des-acyl ghrelin (DAG) and reduced glucose concentrations in the blood. Additionally, administering 10 mg/kg of acyl ghrelin (AG) to a different cohort of animals significantly decreased the amount of time females spent with a potential mating partner, increased the amount of time females spent with food, decreased the duration of lordosis, and increased the duration of eating. Results from the current study support the need for further research investigating the reproductive and ingestive roles of PK2 and ghrelin.

The mammalian body is a complex physiologic "ecosystem" in which cells compete for calories (i.e., nutrient-energy). Axiomatically, cell-types with competitive advantages acquire a greater number of consumed calories, and when possible, increase in size and/or number. Thus, it is logical and parsimonious to posit that obesity is the competitive advantages of fat-cells (adipocytes) driving a disproportionate acquisition and storage of nutrient-energy. Accordingly, we introduce two conceptual frameworks. Asymmetric Nutrient-Energy Partitioning describes the context-dependent, cell-specific competition for calories that determines the partitioning of nutrient-energy to oxidation, anabolism, and/or storage; and Effective Caloric Intake which describes the number of calories available to constrain energy-intake via the inhibition of the sensorimotor appetitive cells in the liver and brain that govern ingestive behaviors. Inherent in these frameworks is the independence and dissociation of the energetic demands of metabolism and the neuro-muscular pathways that initiate ingestive behaviors and energy intake. As we demonstrate, if the sensorimotor cells suffer relative caloric deprivation via asymmetric competition from other cell-types (e.g., skeletal muscle- or fat-cells), energy-intake is increased to compensate for both real and merely apparent deficits in energy-homeostasis (i.e., true and false signals, respectively). Thus, we posit that the chronic positive energy balance (i.e., over-nutrition) that leads to obesity and metabolic diseases is engendered by apparent deficits (i.e., false signals) driven by the asymmetric inter-cellular competition for calories and concomitant differential partitioning of nutrient-energy to storage. These frameworks, in concert with our previous theoretic work, the Maternal Resources Hypothesis, provide a parsimonious and rigorous explanation for the rapid rise in the global prevalence of increased body and fat mass, and associated metabolic dysfunctions in humans and other mammals inclusive of companion, domesticated, laboratory, and feral animals.

Serotonin 1A receptors (5-HT1ARs), which are widely distributed in the mammalian brain, participate in cognitive and emotional functions. In birds, 5-HT1ARs are expressed in prosencephalic areas involved in visual and cognitive functions. Diverse evidence supports 5-HT1AR-mediated 5-HT-induced ingestive and sleep behaviors in birds. Here, we describe the distribution of 5-HT1ARs in the hypothalamus and brainstem of birds, analyze their potential roles in sleep and ingestive behaviors, and attempt to determine the involvement of auto-/hetero-5-HT1ARs in these behaviors. In 6 pigeons, the anatomical distribution of [(3)H]8-OH-DPAT binding in the rostral brainstem and hypothalamus was examined. Ingestive/sleep behaviors were recorded (1h) in 16 pigeons pretreated with MM77 (a heterosynaptic 5-HT1AR antagonist; 23 or 69 nmol) for 20 min, followed by intracerebroventricular ICV injection of 5-HT (N:8; 150 nmol), 8-OH-DPAT (DPAT, a 5-HT1A,7R agonist, 30 nmol N:8) or vehicle. 5-HT- and DPAT-induced sleep and ingestive behaviors, brainstem 5-HT neuronal density and brain 5-HT content were examined in 12 pigeons, pretreated by ICV with the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (N:6/group). The distribution of brainstem and diencephalic c-Fos immunoreactivity after ICV injection of 5-HT, DPAT or vehicle (N:5/group) into birds provided with or denied access to water is also described. 5-HT1ARs are concentrated in the brainstem 5-HTergic areas and throughout the periventricular hypothalamus, preoptic nuclei and circumventricular organs. 5-HT and DPAT produced a complex c-Fos expression pattern in the 5-HT1AR-enriched preoptic hypothalamus and the circumventricular organs, which are related to drinking and sleep regulation, but modestly affected c-Fos expression in 5-HTergic neurons. The 5-HT-induced ingestivebehaviors and the 5-HT- and DPAT-induced sleep behaviors were reduced by MM77 pretreatment. 5,7-DHT increased sleep per se, decreased tryptophan hydroxylase expression in the raphe nuclei and decreased prosencephalic 5-HT release but failed to affect 5-HT- or DPAT-induced drinking or sleep behavior. 5-HT- and DPAT-induced ingestive and sleep behaviors in pigeons appear to be mediated by heterosynaptic and/or non-somatodendritic presynaptic 5-HT1ARs localized to periventricular diencephalic circuits.

Ingestive behaviors in mice are dependent on orosensory cues transmitted via the trigeminal nerve, as confirmed by transection studies. However, these studies cannot differentiate between deficits caused by the loss of the lemniscal pathway vs. the parallel paralemniscal pathway. The paired-like homeodomain protein Prrxl1 is expressed widely in the brain and spinal cord, including the trigeminal system. A knockout of Prrxl1 abolishes somatotopic barrellette patterning in the lemniscal brainstem nucleus, but not in the parallel paralemniscal nucleus. Null animals are significantly smaller than littermates by postnatal day 5, but reach developmental landmarks at appropriate times, and survive to adulthood on liquid diet. A careful analysis of infant and adult ingestive behavior reveals subtle impairments in suckling, increases in time spent feeding and the duration of feeding bouts, feeding during inappropriate times of the day, and difficulties in the mechanics of feeding. During liquid diet feeding, null mice display abnormal behaviors including extensive use of the paws to move food into the mouth, submerging the snout in the diet, changes in licking, and also have difficulty consuming solid chow pellets. We suggest that our Prrxl1(-/-) animal is a valuable model system for examining the genetic assembly and functional role of trigeminal lemniscal circuits in the normal control of eating in mammals and for understanding feeding abnormalities in humans resulting from the abnormal development of these circuits.