Food-seeking Behavior Research Articles

TLR4-dependent neuroinflammation mediates LPS-driven food-reward alterations during high-fat exposure

BackgroundObesity has become a global pandemic, marked by significant shifts in both the homeostatic and hedonic/reward aspects of food consumption. While the precise causes are still under investigation, recent studies have identified the role of gut microbes in dysregulating the reward system within the context of obesity. Unravelling these gut–brain connections is crucial for developing effective interventions against eating and metabolic disorders, particularly in the context of obesity. This study explores the causal role of LPS, as a key relay of microbiota component-induced neuroinflammation in the dysregulation of the reward system following exposure to high-fat diet (HFD).MethodsThrough a series of behavioural paradigms related to food-reward events and the use of pharmacological agents targeting the dopamine circuit, we investigated the mechanisms associated with the development of reward dysregulation during HFD-feeding in male mice. A Toll-like receptor 4 (TLR4) full knockout model and intraventricular lipopolysaccharide (LPS) diffusion at low doses, which mimics the obesity-associated neuroinflammatory phenotype, were used to investigate the causal roles of gut microbiota-derived components in neuroinflammation and reward dysregulation.ResultsOur study revealed that short term exposure to HFD (24 h) tended to affect food-seeking behaviour, and this effect became significant after 1 week of HFD. Moreover, we found that deletion of TLR4 induced a partial protection against HFD-induced neuroinflammation and reward dysregulation. Finally, chronic brain diffusion of LPS recapitulated, at least in part, HFD-induced molecular and behavioural dysfunctions within the reward system.ConclusionsThese findings highlight a link between the neuroinflammatory processes triggered by the gut microbiota components LPS and the dysregulation of the reward system during HFD-induced obesity through the TLR4 pathway, thus paving the way for future therapeutic approaches.Graphical abstract

Food intake enhances hippocampal sharp wave-ripples.

Effective regulation of energy metabolism is critical for survival. Metabolic control involves various nuclei within the hypothalamus, which receive information about the body's energy state and coordinate appropriate responses to maintain homeostasis, such as thermogenesis, pancreatic insulin secretion, and food-seeking behaviors. It has recently been found that the hippocampus, a brain region traditionally associated with memory and spatial navigation, is also involved in metabolic regulation. Specifically, hippocampal sharp wave ripples (SWRs), which are high-frequency neural oscillations supporting memory consolidation and foraging decisions, have been shown to influence peripheral glucose metabolism. However, whether SWRs are enhanced by recent feeding-when the need for glucose metabolism increases, and if so, whether feeding-dependent modulation of SWRs is communicated to other brain regions involved in metabolic regulation, remains unknown. To address these gaps, we recorded SWRs from the dorsal CA1 region of the hippocampus of mice during sleep sessions before and after consumption of meals of varying caloric values. We found that SWRs occurring during sleep are significantly enhanced following food intake, with the magnitude of enhancement being dependent on the caloric content of the meal. This pattern occurred under both food-deprived and ad libitum feeding conditions. Moreover, we demonstrate that GABAergic neurons in the lateral hypothalamus, which are known to regulate food intake, exhibit a robust SWR-triggered increase in activity. These findings identify the satiety state as a factor modulating SWRs and suggest that hippocampal-lateral hypothalamic communication is a potential mechanism by which SWRs could modulate peripheral metabolism and food intake.

The amino acid composition of a protein influences its expression.

The quantity of each protein in a cell only is only partially correlated with its gene transcription rate. Independent influences on protein synthesis levels include mRNA sequence motifs, amino acyl-tRNA synthesis levels, elongation factor action, and protein susceptibility to degradation. Here we report that the amino acid composition of a protein can also influence its expression level in two distinct ways. The nutritional classification of amino acids in animals reflects their potential for scarcity-essential amino acids (EAA) are reliant on dietary supply, non-essential amino acids (NEAA) from internal biosynthesis, and conditionally essential amino acids (CEAA) from both. Accessing public proteomic datasets, we demonstrate that a protein's CEAA sequence composition is inversely correlated with expression-a correlation enhanced during rapid cellular proliferation-suggesting CEAA availability can limit translation. Similarly, proteins with the most extreme compositions of EAA are generally reduced in abundance. These latter proteins participate in biological systems such as taste and food-seeking behaviour, oxidative phosphorylation, and chemokine function, and so linking their expression to EAA availability may act as a homeostatic response to malnutrition. Protein composition can also influence general human phenotypes and disease susceptibility: stature proteins are enriched in CEAAs, and a curated dataset of over 700 cancer proteins is significantly under-represented in EAAs. We also show that individual amino acids can influence protein expression across all kingdoms of life and that this effect appears to be rooted in the unchanging structural and mRNA encoding features of each amino acid. Species-specific environmental survival pathways are shown to be enriched in proteins with individual amino acid compositions favouring higher expression. These two forms of amino acid-driven protein expression regulation promise new insights into systems biology, evolutionary studies, experimental research design, and public health intervention.

12418 Patient- And Caregiver-reported Experiences Of Hunger, Weight, And Energy In Acquired Hypothalamic Obesity Before And During Setmelanotide Treatment

Abstract Disclosure: C.L. Roth: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Saniona, Rhythm Pharmaceuticals, Inc. Speaker; Self; Saniona, Rhythm Pharmaceuticals, Inc. C. Ervin: Other; Self; Rhythm Pharmaceuticals, Inc. L. Norcross: Other; Self; Rhythm Pharmaceuticals, Inc. S. Fehnel: Other; Self; Rhythm Pharmaceuticals, Inc. C. Huber: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. M.J. Abuzzahab: Consulting Fee; Self; Rhythm Pharmaceuticals, Inc., Ascendis, Novo Nordisk, Lumos, Soleno, Pfizer, Inc.. Speaker; Self; Rhythm Pharmaceuticals, Inc., Ascendis, Novo Nordisk, Lumos, Soleno, Pfizer, Inc.. Background: Acquired hypothalamic obesity (HO) is a rapid-onset, severe obesity caused by hypothalamic injury that may impair melanocortin-4 receptor (MC4R) pathway signaling and lead to hyperphagia, decreased energy expenditure, and severe obesity, for which no approved therapies exist. We describe experiences or caregiver observations of hunger, weight, and energy in patients with HO before and after investigational treatment with the MC4R agonist setmelanotide. Methods: In-depth qualitative interviews were conducted via Zoom by 2 members of the study team with patients or caregivers of patients who completed a Phase 2 trial of setmelanotide (NCT04725240) and enrolled in the open-label long-term extension (NCT03651765). Eligible patients were aged ≥12 years and eligible caregivers were aged ≥18 years and full-time caregivers of patients aged <12 years or unable to self-report. Interview transcripts were analyzed using a thematic approach. Results: Five participants (3 patients, 2 caregivers) completed interviews. After hypothalamic damage (before setmelanotide), all participants described unrelenting hunger, drastically reduced energy or physical activity, and substantial weight gain negatively impacting self-esteem, emotions, and family dynamics. With setmelanotide, all participants reported reduced weight or body mass index, and 4 reported reduced hunger, which was accompanied by improved food-seeking behaviors, sleep (eg, not waking at night for food), self-confidence, and mood. Participants identified reduced hunger and weight and improved emotions or mood as the most important treatment benefits. Additional benefits were improved social engagement, physical activity, and school/work performance. All reported satisfaction and a desire to continue setmelanotide. Conclusions: Patients experienced negative consequences of hypothalamic damage on hunger, weight, and energy that were alleviated by setmelanotide, resulting in broad benefits for patients and caregivers. Presentation: 6/1/2024

Growth Hormone Receptor in Lateral Hypothalamic Neurons Is Required for Increased Food-Seeking Behavior during Food Restriction in Male Mice.

Growth hormone (GH) action in the brain regulates neuroendocrine axes, energy and glucose homeostasis, and several neurological functions. The lateral hypothalamic area (LHA) contains numerous neurons that respond to a systemic GH injection by expressing the phosphorylated STAT5, a GH receptor (GHR) signaling marker. However, the potential role of GHR signaling in the LHA is unknown. In this study, we demonstrated that ∼70% of orexin- and leptin receptor (LepR)-expressing neurons in the LHA are responsive to GH. Male mice carrying inactivation of the Ghr gene in the LHA were generated via bilateral injections of an adeno-associated virus. In ad libitum-fed mice, GHR ablation in LHA neurons did not significantly change energy and glucose homeostasis. Subsequently, mice were subjected to 5 d of 40% food restriction. Food restriction decreased body weight, energy expenditure, and carbohydrate oxidation. These effects were similarly observed in control and LHAΔGHR mice. While food-deprived control mice progressively increased ambulatory/exploratory activity and food-seeking behavior, LHAΔGHR mice did not show hyperactivity induced by food restriction. GHR ablation in the LHA reduced the percentage of orexin neurons expressing c-Fos during food restriction. Additionally, an acute GH injection increased the expression of c-Fos in LHAORX neurons. Inactivation of Ghr in LepR-expressing cells did not prevent hyperactivity in food-deprived mice, whereas whole-brain Ghr knock-out mice showed reduced ambulatory activity during food restriction. Our findings indicate that GHR signaling in the LHA regulates the activity of orexin neurons and is necessary to increase food-seeking behavior in food-deprived male mice.

Foodinsecurity.london: Developing a food-insecurity prevalence map for London - a machine learning from food-sharing footprints

Introduction & BackgroundThe ability of policymakers to positively transform food environments requires robust empirical evidence that can inform decisions. At present, there is limited data on food-insecurity in the UK that can be used to inform interventions by local authorities, due to the prohibitive costs and logistical challenges of administering longitudinal surveys. This study builds on existing research and a key pilot study developed in partnership between Olio - a food-sharing app with 7 million registered users as of 2023, the University of Nottingham and Havering Council in 2020, which resulted in the world’s first map prototype of food-insecurity. Objectives & ApproachOur approach leverages Machine Learning methods applied to unprecedented food-acquisition behavioural data and open area-level deprivation statistics to model and predict individuals' experience of food-insecurity across London. We used Olio’s extensive network of users to distribute 2,849 surveys, asking respondents across London about their experiences of food-insecurity. The survey was distributed online, adapting the US Department of Agriculture Food Security module. Respondents were asked about their experiences, including (1) eating smaller meals or skipping meals, (2) being hungry but being unable to eat, and (3) not eating for a whole day, because they could not afford food or because they could not get access to food. Using the household, rather than the individual-level version of the food insecurity module helped shed light on the experience of vulnerable groups - such as children. Relevance to Digital FootprintsThe survey responses provided a ground truth about users' experiences of destitution. Deprivation metrics and digital footprint data in the form of food-acquisition behavioural data were then used in a Random Forests Machine Learning model to predict whether households were experiencing food-insecurity, achieving high accuracy. Food-sharing data from almost 50,000 London-based users active on Olio’s platform were then used to identify relevant food-seeking behaviours and aggregate recognised instances of food-insecurity at neighbourhood (MSOA) level. Conclusions & ImplicationsTo identify and rank relevant socio-demographics and food-seeking behaviours most informative for describing food-insecurity an extensive variable selection analysis was performed. The resulting SHAP (SHapley Additive exPlanations) values showed that a combination of food solicitation and the general deprivation of an area were important predictors of food-insecurity.

After a period of forced abstinence, rats treated with the norepinephrine neurotoxin DSP-4 still exhibit preserved food-seeking behavior and prefrontal cortex fos-expressing neurons

AimsRelapse is a common characteristic of compulsive behaviors like addiction, where individuals tend to return to drug use or overeating after a period of abstinence. PFC (prefrontal cortex) neuronal ensembles are required for drug and food-seeking behaviors and are partially regulated by Norepinephrine (NE). However, the contributions of neuromodulators, such as the adrenergic system, in food-seeking behavior are not fully understood. Main methodsTo investigate this, we trained male and female rats to press a lever in an operant chamber to obtain banana-flavored food pellets for ten days. We then administered DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride), a neurotoxin that diminishes norepinephrine levels in the brain. The rats were kept in their home cages for ten more days before being returned to the operant chambers to measure food-seeking behavior. Key findingsDespite receiving DSP-4, the PFC neuronal ensembles measured by Fos and food-seeking behavior did not differ between groups, but rather sex. SignificanceAlthough both NE and Fos expressing neurons are implicated in food-seeking, they do not seem to be involved in a cue-contextual induced re-exposure response.

Quality of Life for Adults with Prader-Willi Syndrome in Residential Group Homes.

Background: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home environments. PWS-specialized hostels (SH) succeed in preventing morbid obesity and in coping with behavioral disorders; however, effects of restricted living environments on quality of life (QOL) have not been described. Evidence on QOL is critical for clinicians involved in placement decisions. Methods: We examined the impact of living in SH versus at home or in non-specialized hostels (H and NSH) on QOL, behavior, and health parameters. All 58 adults (26 males) followed-up in the National Multidisciplinary Clinic for PWS were included: 33 resided in SH, 18 lived at home, and 7 lived in NSH. Questionnaires were administered to primary caregivers to measure QOL, and data were obtained from the medical records. Results: The H and NSH group were compared with those for adults in SH. Despite strict diet and exercise regimens, QOL was similar for both groups. Eight-year follow-up showed that food-seeking behavior decreased in SH but increased in H and NSH. BMI, cholesterol, and triglyceride levels were lower in SH. Conclusion: Our results suggest that living in SH is associated with benefits for physical health and behavior without negatively affecting QOL.

Ceftriaxone reverses diet-induced deficits in goal-directed control.

Obesity is associated with numerous health risks and ever-increasing rates are a significant global concern. However, despite weight loss attempts many people have difficulty maintaining weight loss. Previous studies in animals have shown that chronic access to an obesogenic diet can disrupt goal-directed behavior, impairing the ability of animals to flexibly adjust food-seeking behavior following changes in the value of earned outcomes. Changes in behavioral control have been linked to disruption of glutamate transmission in the dorsal medial striatum (DMS), a region critical for the acquisition and expression of goal-directed behavior. The goal of this study was to test whether ceftriaxone, a beta-lactam antibiotic shown elsewhere to upregulate the expression of the glutamate transporter GLT-1, would improve goal-directed control following long-term exposure to an obesogenic diet. Male and female rats were given access to either standard chow or chow plus sweetened condensed milk (SCM) for 6 weeks. Access to SCM was ended and rats received daily injections of either ceftriaxone or saline for 6 days. Rats were then trained to press a lever to earn a novel food reward and, finally, were assessed for sensitivity to outcome devaluation. Histological analyses examined changes to GLT-1 protein levels and morphological changes to astrocytes, within the DMS. We found that ceftriaxone robustly restored goal-directed behavior in animals following long-term exposure to SCM. While we did not observe changes in protein levels of GLT-1 in the DMS, we observed that SCM induced changes in the morphology of astrocytes in the DMS, and that ceftriaxone mitigated these changes. These results demonstrate that long-term access to a SCM diet impairs goal-directed behavior while also altering the morphology of astrocytes in the DMS. Furthermore, these results suggest that ceftriaxone administration can reverse the impairment of goal-directed behavior potentially through its actions on astrocytes in decision-making circuitry.

Load frequency control of multi-area power system incorporated renewable energy considering electrical vehicle effect using modified cascaded controller tuned by BESSO algorithm

In power systems, load frequency control (LFC) matters significantly to achieve stability. Dealing with the fluctuations in the frequency of a multi-area power system becomes more challenging by incorporating additional energy resources. In this research, a multi-area power system is built by integrating thermal power systems with photovoltaic (PV) cells, wind turbines, and electric vehicles (EV). The addition of an electric vehicle “to a thermal power system which is integrated with a renewable energy source (RES)” increases the system productivity but also increases the system complexity, making it more problematic for LFC. Looking at the stability criteria for LFC, frequencies in two areas (Area-1 & Area-2) and tie-line power are considered for measurements. For the tuning of the proposed cascaded (1+PI)-PID controller, a new approach Bald Eagle Sparrow Search Optimization (BESSO) algorithm is implemented which is strongly inspired by nature. BESSO is a combination of bald eagle and sparrow searching techniques and performs comparatively better for fast convergence due to their strong food-seeking natural behavior to find the best solution for controller gains. Controller effects on multi-area systems are compared with the addition of PV, wind, and EV and resulting measurements meet the stability criteria with high accuracy even with the complexity of the system and also undertake a stability analysis to prove the performance by minimizing undershoot, overshoot, steady-state error and settling time for system frequencies and tie-line power. Simulation results are examined at different load-changing conditions. In contrast with similar combinations of PID controller with proposed cascaded (1+PI)-PID controller, it is claimed that the effect of the proposed controller is much finer and more reliable, even with electric vehicles to avoid system blackout caused by frequency fluctuations in interconnected power system.

Control of motivation for sucrose in the paraventricular hypothalamic nucleus by dynorphin peptides and the kappa opioid receptor

The dynorphin peptides are the endogenous ligands for the kappa opioid receptor (KOR) and regulate food intake. Administration of dynorphin-A1-13 (DYN) in the paraventricular hypothalamic nucleus (PVN) increases palatable food intake, and this effect is blocked by co-administration of the orexin-A neuropeptide, which is co-released with DYN in PVN from neurons located in the lateral hypothalamus. While PVN administration of DYN increases palatable food intake, whether it increases food-seeking behaviors has yet to be examined. We tested the effects of DYN and norBNI (a KOR antagonist) on the seeking and consumption of sucrose using a progressive ratio (PR) and demand curve (DC) tasks. In PVN, DYN did not alter the sucrose breaking point (BP) in the PR task nor the elasticity or intensity of demand for sucrose in the DC task. Still, DYN reduced the delay in obtaining sucrose and increased licks during sucrose intake in the PR task, irrespective of the co-administration of orexin-A. In PVN, norBNI increased the delay in obtaining sucrose and reduced licks during sucrose intake in the PR task while increasing elasticity without altering intensity of demand in the DC task. However, subcutaneous norBNI reduced the BP for sucrose and increased the delay in obtaining sucrose in the PR task while reducing the elasticity of demand. Together, these data show different effects of systemic and PVN blockade of KOR on food-seeking, consummatory behaviors, and incentive motivation for sucrose and suggest that KOR activity in PVN is necessary but not sufficient to drive seeking behaviors for palatable food.

Preference of position in the proximity of various sugars revealed by location analysis of Drosophila melanogaster

Feeding behaviors are determined by two main factors. One is the internal state, such as hunger or previous experiences; the other is external factors, such as sensory stimulation. During starvation, animals must balance food-seeking behavior with energy conservation. The fruit fly, Drosophila melanogaster, serves as a useful model for studying food selectivity and various behaviors related to food intake. However, few studies have directly connected food selectivity with other behaviors, such as locomotor activity and sleep. In this study, we report that flies exhibited a preference for specific positions and spent more time in the proximity of sweet sugars, such as sucrose and sucralose, but not non-sweet and nutritious sugars like xylitol and sorbitol. On the other hand, prolonged exposure to sorbitol increased the staying time of flies in the proximity of sorbitol. Additionally, after starvation, flies immediately exhibited a position preference in the proximity of sorbitol. These findings suggest that flies prefer the proximity of sweet food, and starvation alters their preference for nutritious food, which may be beneficial for their survival.

Blind cavefish evolved higher foraging responses to chemo- and mechanostimuli.

In nature, animals must navigate to forage according to their sensory inputs. Different species use different sensory modalities to locate food efficiently. For teleosts, food emits visual, mechanical, chemical, and/or possibly weak-electrical signals, which can be detected by optic, auditory/lateral line, and olfactory/taste buds sensory systems. However, how fish respond to and use different sensory inputs when locating food, as well as the evolution of these sensory modalities, remain unclear. We examined the Mexican tetra, Astyanax mexicanus, which is composed of two different morphs: a sighted riverine (surface fish) and a blind cave morph (cavefish). Compared with surface fish, cavefish have enhanced non-visual sensory systems, including the mechanosensory lateral line system, chemical sensors comprising the olfactory system and taste buds, and the auditory system to help navigate toward food sources. We tested how visual, chemical, and mechanical stimuli evoke food-seeking behavior. In contrast to our expectations, both surface fish and cavefish did not follow a gradient of chemical stimulus (food extract) but used it as a cue for the ambient existence of food. Surface fish followed visual cues (red plastic beads and food pellets), but, in the dark, were likely to rely on mechanosensors-the lateral line and/or tactile sensor-as cavefish did. Our results indicate cavefish used a similar sensory modality to surface fish in the dark, while affinity levels to stimuli were higher in cavefish. In addition, cavefish evolved an extended circling strategy to forage, which may yield a higher chance to capture food by swimming-by the food multiple times instead of once through zigzag motion. In summary, we propose that ancestors of cavefish, similar to the modern surface fish, evolved extended food-seeking behaviors, including circling motion, to adapt to the dark.

Effects of handling and surgical implant on juvenile wild trout: Physiological and behavioral impact.

Fish involved in telemetry studies are usually handled, anaesthetized, and subjected to internal tag implantation, all of which have the potential to disrupt the fish's physiology, migratory patterns, food-seeking behavior, growth, and survival. As fish tagging is a widespread standard method in aquaculture, it is crucial to gain a better understanding of the short- and long-term effects on various aspects of fish welfare. The experimental outcomes of each phase of the surgical process and how it affects the fish's ability to recover during the post-tagging period, particularly in small salmonids, are poorly understood. Thus, it is essential to measure the extent of these adverse effects to precisely extrapolate differences in surgical intervention for tagged fish compared to their unmanipulated counterparts. In our study, we explored the post-tagging impacts on wild-captured brown trout (Salmo trutta) (1+) juveniles. We examined the time effect on fish recovery after each phase of the surgical procedure, which included anaesthetized fish, followed by surgery with/without internal tagging, within the first 2 and 25 h post-surgery. Common blood parameters (glucose levels and haematocrit) and endpoints related to swimming behavior, including fish movement, direction, and social distancing aspects, were studied. The findings of the study indicated no significant changes in glucose and haematocrit levels over the observational period. Fish subjected to anesthesia and tagging procedures exhibited a significant decrease in swimming activity, recovering to baseline levels 1 h after anesthesia and 24 h after surgical (tagging) procedures in recirculating aquaculture systems. Tagged fish showed less social proximity than non-tagged fish in the first 2 h post-surgery. A significant effect size was observed between nonsurgical (anesthesia) and surgical (non-tagged/tagged) groups, highlighting a more pronounced impact associated with surgical tag interventions. Our data indicate that the magnitude of behavioral response was significantly influenced by tag weight (~1.4% body/tag weight ratio in water) among manipulated fish groups. Consequently, our study reveals that wild-captured S. trutta juveniles, tagged with commercially available low-weight acoustic tags (V6, 69 kHz), experienced negative effects on swimming performance. In surgical studies, acknowledging potential influences is crucial for accurately inferring fish physiological and behavioral status. Emphasizing fish recovery potential in both short- and long-term periods is essential for quantifying tagging effects. Future research should prioritize exploring alternative tagging technologies and refining methodologies, with a particular focus on assessing telemetry's impact on socioeconomically relevant small salmonids.

Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment.

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.

A single incidental dark pulse during daytime attenuated food anticipatory behavior

ABSTRACT Using an open-source operant feeding device (FED3), we measured food-seeking nose poking behavior in mice. When the mice were exposed to 4 h restricted feeding at night, all mice exhibited robust food anticipatory nose poking starting ~4 h before scheduled mealtime. When the light-dark cycle was advanced by 6 h, mice exhibited two distinct bouts of anticipatory poking, one corresponding to actual mealtime which continued at the same time of day, and one corresponding to predicted mealtime which shifted parallel with the light-dark cycle. Likewise, two similar bouts of food-seeking behavior appeared when the light-dark cycle was delayed for 9 h. These data suggest that food anticipatory behavior is encoded to a circadian oscillator that entrains to the light-dark cycle. Two weeks after advancing the light-dark cycle, mice incidentally received a 3.5 h dark pulse in the middle of the day. This single dark pulse had a negligible effect on running wheel behavior but caused a temporary attenuation of both food anticipatory poking and pellet intake. These results suggest that the circadian oscillator controlling food anticipatory poking is sensitive to light disruption and that proper food anticipation is critical for sufficient food intake during temporally restricted feeding.

Optogenetic stimulation of the locus coeruleus enhances appetitive extinction in rats

Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.

Optogenetic stimulation of the locus coeruleus enhances appetitive extinction in rats.

Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.

Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite

The neurobiological mechanisms that regulate the appetite-stimulatory properties of cannabis sativa are unresolved. This work examined the hypothesis that cannabinoid-1 receptor (CB1R) expressing neurons in the mediobasal hypothalamus (MBH) regulate increased appetite following cannabis vapor inhalation. Here we utilized a paradigm where vaporized cannabis plant matter was administered passively to rodents. Initial studies in rats characterized meal patterns and operant responding for palatable food following exposure to air or vapor cannabis. Studies conducted in mice used a combination of in vivo optical imaging, electrophysiology and chemogenetic manipulations to determine the importance of MBH neurons for cannabis-induced feeding behavior. Our data indicate that cannabis vapor increased meal frequency and food seeking behavior without altering locomotor activity. Importantly, we observed augmented MBH activity within distinct neuronal populations when mice anticipated or consumed food. Mechanistic experiments demonstrated that pharmacological activation of CB1R attenuated inhibitory synaptic tone onto hunger promoting Agouti Related Peptide (AgRP) neurons within the MBH. Lastly, chemogenetic inhibition of AgRP neurons attenuated the appetite promoting effects of cannabis vapor. Based on these results, we conclude that MBH neurons contribute to the appetite stimulatory properties of inhaled cannabis.

Early-life caffeine exposure induces morphological changes and altered physiology in Caenorhabditiselegans

Caffeine, a widely consumed stimulant, is known for its effects on alertness and fatigue reduction by blockade of adenosine receptors. While it holds therapeutic potential, its diverse impacts pose risks, particularly in early development. This study explores the developmental effects of caffeine exposure using Caenorhabditis elegans (C. elegans) as a model organism. We investigated morphological and behavioral changes induced by caffeine exposure at the L1 stage and assessed their impact at the L4 stage, which roughly corresponds to human infancy and adolescence, respectively. Caffeine-exposed worms displayed increased body length, body bends, and pharyngeal pumping rates compared to control worms. These findings indicate heightened food-seeking behavior and greater food intake, leading to the observed morphological changes. While caffeine did not affect other locomotor behaviors, its stimulatory effect on growth and development highlights its significance. This study provides insights into the potential impact of early-life caffeine exposure on long-term health and development, offering a foundation for future research in vertebrates to uncover its implications on metabolism and other metrics of health.