A hippocampus-accumbens code guides goal-directed appetitive behavior.

The dorsal hippocampus (dHPC) is a key brain region for the expression of spatial memories, such as navigating towards a learned reward location. The nucleus accumbens (NAc) is a prominent projection target of dHPC and implicated in value-based action selection. Yet, the contents of the dHPC→NAc information stream and their acute role in behavior remain largely unknown. Here, we found that optogenetic stimulation of the dHPC→NAc pathway while mice navigated towards a learned reward location was both necessary and sufficient for spatial memory-related appetitive behaviors. To understand the task-relevant coding properties of individual NAc-projecting hippocampal neurons (dHPC→NAc), we used in vivo dual-color two-photon imaging. In contrast to other dHPC neurons, the dHPC→NAc subpopulation contained more place cells, with enriched spatial tuning properties. This subpopulation also showed enhanced coding of non-spatial task-relevant behaviors such as deceleration and appetitive licking. A generalized linear model revealed enhanced conjunctive coding in dHPC→NAc neurons which improved the identification of the reward zone. We propose that dHPC routes specific reward-related spatial and behavioral state information to guide NAc action selection.

Encoding of Predictive Associations in Human Prefrontal and Medial Temporal Neurons During Pavlovian Appetitive Conditioning.

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here, we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus, and amygdala while patients of both sexes performed an appetitive Pavlovian conditioning task probing both stimulus-value and stimulus-stimulus associations. Ventromedial prefrontal cortex encoded predictive value along with the amygdala, and also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial frontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning.

The effect of fear on health information searching behavior during the pandemic: The case of COVID-19.

BACKGROUND AND OBJECTIVES: Fear can cause people to panic, lead to erroneous decisions, and trigger inappropriate behavior. This study aims to investigate the effects of fear of COVID-19 on the perception of the reliability and the use of health information sources. METHODS: This study is both a cross-sectional and explanatory study. The participants selected by convenience sampling method were 323 students attending a state university in Turkey. The Fear of COVID-19 Scale (FCV-19S) and the Health Information Sources Survey were used as data collection tools. Descriptive statistics, correlation coefficients, and linear regression analyses were used. RESULTS: The participants' mean FCV-19S score was 2.30 ± 0.93 on a five-point Likert scale. In the range of 0-10, the information source with the highest reliability perception mean score was the doctor (8.05 ± 2.54), whereas that with the highest usage was the Internet (7.98 ± 2.77). Although the fear of COVID-19 had a negative effect on Internet use (b = -0.38; p < 0.05), the effects on the use of other health information sources were positive (b = 0.37-0.83; p < 0.05). Trust in radio (b = 0.60; p < 0.05) and newspapers/magazines (b = 0.49; p < 0.05) also increased with fear. CONCLUSIONS: These results showed that as university students' fear of COVID-19 increased, the use of the Internet for health information decreased; however, the use of doctors, nurses, pharmacists, other health workers, scientific articles, television, radio, and newspapers/journals increased. Nurses were the source of information whose use increased the most, along with increased fear. The findings can guide health policies to be followed. Not only doctor talks but also nurse talks and scientific videos should be increased on the Internet, social media, and other mass media.

A search for effective reinforcers in appetitive conditioning for adult zebrafish: Ecologically relevant unconditioned stimuli.

Learning and memory related brain disorders represent a large unmet medical need. Laboratory studies with animals may model brain disorders and facilitate uncovering their mechanisms. The zebrafish has been proposed for such studies. However, numerous factors that influence performance in learning tasks have yet to be understood in zebrafish. One such factor is what motivates zebrafish. Here we introduce a novel reinforcer, an ecologically relevant unconditioned stimulus (US). We placed a photograph of gravel underneath quarter of the bottom of an experimental tank on one side and also positioned artificial plants there, the "natural" US. First, we showed that this stimulus was preferred by zebrafish. Next, we investigated whether this stimulus could serve as US for associative learning. We marked the walls of the tank on the side where the US was presented with red paper, the conditioned stimulus (CS+) we found neutral before, and we also marked the walls on the other side of the tank where no US was placed with blue paper (CS-). In addition to fish receiving this "paired" training, we also ran unpaired training with another group of zebrafish, in which the fish saw the US associated with blue and red in a random manner. After having trained the fish in this manner, we tested the performance of the paired and unpaired group of zebrafish in a memory probe trial during which no US was present, and only the CSs (blue and red walls) were shown. We found the paired group of zebrafish to show significant preference for the CS+, as they spent more time and swam closer to the red side compared to the unpaired group and compared to chance. We conclude that ecologically relevant stimuli can serve as efficient US in appetitive conditioning of zebrafish.

Changes in searching behaviour of CSL transcription complexes in Notch active conditions.

During development cells receive a variety of signals, which are of crucial importance to their fate determination. One such source of signal is the Notch signalling pathway, where Notch activity regulates expression of target genes through the core transcription factor CSL. To understand changes in transcription factor behaviour that lead to transcriptional changes in Notch active cells, we have probed CSL behaviours in real time, using in vivo Single Molecule Localisation Microscopy. Trajectory analysis reveals that Notch-On conditions increase the fraction of bound CSL molecules, but also the proportion of molecules with exploratory behaviours. These properties are shared by the co-activator Mastermind. Furthermore, both CSL and Mastermind, exhibit characteristics of local exploration near a Notch target locus. A similar behaviour is observed for CSL molecules diffusing in the vicinity of other bound CSL clusters. We suggest therefore that CSL acquires an exploratory behaviour when part of the activation complex, favouring local searching and retention close to its target enhancers. This change explains how CSL can efficiently increase its occupancy at target sites in Notch-On conditions.

Tracking Sugar-Elicited Local Searching Behavior in Drosophila.

Foraging behavior is essential for the survival of organisms as it enables them to locate and acquire essential food resources. In Drosophila, hunger triggers a distinct search behavior following the consumption of small quantities of a sugar solution. This report presents a simple experimental setup to study sugar-elicited search behavior with the aim of uncovering the underlying mechanisms. Minute quantities of concentrated sugar solution elicit sustained searching behavior in flies. The involvement of path integration in this behavior has been established, as flies utilize their trajectory to return to the sugar location. The most recent findings provide evidence of temporal modulation in the initiation and intensity of the search behavior after sugar intake. We have also used this setup for artificial activation of specific taste-receptor neurons in the pharynx, which elicits the search behavior. The Drosophila neurogenetic toolkit offers a diverse array of tools and techniques that can be combined with the sugar-elicited search behavior paradigm to study the neural and genetic mechanisms underlying foraging. Understanding the neural basis of hunger-driven searching behavior in flies contributes to the field of neurobiology as a whole, offering insights into the regulatory mechanisms that govern feeding behaviors not only in other organisms but also in humans.

A volatilized pyrethroid insecticide from a mosquito repelling device does not impact honey bee foraging and recruitment.

Because nontarget, beneficials, like insect pollinators, may be exposed unintentionally to insecticides, it is important to evaluate the impact of chemical controls on the behaviors performed by insect pollinators in field trials. Here we examine the impact of a portable mosquito repeller, which emits prallethrin, a pyrethroid insecticide, on honey bee foraging and recruitment using a blinded, randomized, paired, parallel group trial. We found no significant effect of the volatilized insecticide on foraging frequency (our primary outcome), waggle dance propensity, waggle dance frequency, and feeder persistency (our secondary outcomes), even though an additional deposition study confirmed that the treatment device was performing appropriately. These results may be useful to consumers that are interested in repelling mosquitos, but also concerned about potential consequences to beneficial insects, such as honey bees.

First evidence of sex-specific responses to chemical cues in tardigrade mate searching behaviour.

Chemical cues are widely used in intraspecific and interspecific communication, either as substances deposited in the substrate or as molecules diffused in water or air. In tardigrades, an emerging microscopic study system, chemical communication and its role in reproduction are poorly known. Here, we assessed sex differences in the detection of (a) short-range diffusing signals and (b) deposited cue trails during the mate-searching behaviour of freely moving virgin male and female Macrobiotus polonicus. We tracked individual behaviour (a) in simultaneous double-choice chambers, where live conspecifics of each sex were presented in water and (b) of freely moving pairs on agar without water. We found that males, but not females, preferentially associated with opposite-sex individuals in trials conducted in water. In contrast, neither sex detected nor followed cues deposited on agar. In conclusion, our study suggests that mate discrimination and approach are male-specific traits and are limited to waterborne chemical cues. These results support the existence of Darwinian sex roles in pre-mating behaviour in an animal group with virtually non-existing sex differences in morphology or ecology.

Exploring the effects of high curvature section distribution and density in termite tunnels on food transport efficiency: A simulation study.

This study explores the food transport efficiency of termite using an individual-based model. Termites are believed to have evolved tunneling patterns that optimize food search and transport efficiency. However, few studies have investigated transport efficiency due to the difficulty of field observations. The model is characterized by four control variables: the number of simulated termites participating in transport (k1), the distribution of high curvature sections of the termite tunnel (k2), a quantity related to the density of the tunnel sections (k3), and the duration of traffic jams (k4). As k3 increases, the total length of the high curvature section decreases. Our simulation results show that the E(k1, k2) maps for k3 and k4 contain two modes: Mode A shows that E decreases with increasing k1 due to an increase in traffic jams, while Mode B shows E increasing with increasing k1 due to a decrease in the density of curved sections and an increase in jamming resolution time. The partial rank correlation coefficient analysis reveals that k1 and k2 have a negative effect on E, while k3 and k4 have a positive effect, with k1 having the greatest influence on E, followed by k3, k4, and k2. The ecological implications of the simulation results are briefly described, and the limitations of the model are discussed.

Behavioral analysis in laboratory rats: Challenges and usefulness of 50-kHz ultrasonic vocalizations.

Many rodent species emit and detect vocalizations in the ultrasonic range. Rats use three classes of ultrasonic vocalizations depending on developmental stage, experience and the behavioral situation. Calls from one class emitted by juvenile and adult rats, the so-called 50-kHz calls, are typical for appetitive and social situations. This review provides a brief historical account on the introduction of 50-kHz calls in behavioral research followed by a survey of their scientific applications focusing on the last five years, where 50-kHz publications reached a climax. Then, specific methodological challenges will be addressed, like how to measure and report 50-kHz USV, the problem of assignment of acoustic signals to a specific sender in a social situation, and individual variability in call propensity. Finally, the intricacy of interpreting 50-kHz results will be discussed focusing on the most prevalent ones, namely as communicative signals and/or readouts of the sender's emotional status.

Caregiver feeding decisions and sociodemographic characteristics are associated with snack food intake during infancy and toddlerhood.

Snacking starts early in childhood, yet little is known about child versus family influences on snacking during infancy and toddlerhood. This secondary analysis of baseline data examined associations of child characteristics (e.g., appetitive traits, temperament), caregiver feeding decisions, and sociodemographic characteristics with the mean frequency of (times/day) and mean energy from (kcal/day) child snack food intake. Caregivers and their children (ages 9-15 months) were recruited in Buffalo, NY from 2017 to 2019. Caregivers reported on sociodemographics, child appetitive traits (Baby Eating Behaviour Questionnaire), and child temperament (Infant Behavior Questionnaire-Revised). Three 24-h dietary recalls were collected, and USDA food categories were used to categorize snack foods (e.g., cookies, chips, and puffs). Hierarchical multiple linear regression models examined associations of child characteristics (Step 1: age, sex, baseline weight-for-length z-score, appetitive traits, and temperament), caregiver feeding decisions (Step 2: breastfeeding duration and age of solid food introduction), and caregiver sociodemographic characteristics (Step 3: caregiver age, prepregnancy BMI, education, and household size) with mean child snack food intake. Caregivers (n = 141) were on average 32.6 years of age, predominantly white (89.1%), and college-educated (84.2%). Age of solid food introduction (B = -0.21, p = 0.03), prepregnancy BMI (B = 0.03, p = 0.04), and household size (B = 0.23, p = 0.02) were significantly associated with the mean frequency of (times/day) snack food intake, over and above other variables of interest. Child age (B = 15.96, p = 0.002) was significantly associated with mean energy from (kcal/day) snack food intake. Household size (B = 28.51, p = 0.006) was significantly associated with mean energy from (kcal/day) snack food intake, over and above other variables of interest. There were no significant associations of other child characteristics with snack food intake. Findings show that child snack food intake is more closely associated with caregiver feeding decisions and sociodemographic characteristics than child characteristics. TRIAL REGISTRATION: National Institute on Child Health and Human Development, Grant/Award Number R01HD087082-01.

From safety to frustration: The neural substrates of inhibitory learning in aversive and appetitive conditioning procedures.

Inhibitory associative learning counters the effects of excitatory learning, whether appetitively or aversively motivated. Moreover, the affective responses accompanying the inhibitory associations are of opponent valence to the excitatory conditioned responses. Inhibitors for negative aversive outcomes (e.g. shock) signal safety, while inhibitors for appetitive outcomes (e.g. food reward) elicit frustration and/or disappointment. This raises the question as to whether studies using appetitive and aversive conditioning procedures should demonstrate the same neural substrates for inhibitory learning. We review the neural substrates of appetitive and aversive inhibitory learning as measured in different procedural variants and in the context of the underpinning excitatory conditioning on which it depends. The mesocorticolimbic dopamine pathways, retrosplenial cortex and hippocampus are consistently implicated in inhibitory learning. Further neural substrates identified in some procedural variants may be related to the specific motivation of the learning task and modalities of the learning cues. Finally, we consider the translational implications of our understanding of the neural substrates of inhibitory learning, for obesity and addictions as well as for anxiety disorders.

Eat, seek, rest? An orexin/hypocretin perspective.

Seeking and ingesting nutrients is an essential cycle of life in all species. In classical neuropsychology these two behaviours are viewed as fundamentally distinct from each other, and known as appetitive and consummatory, respectively. Appetitive behaviour is highly flexible and diverse, but typically involves increased locomotion and spatial exploration. Consummatory behaviour, in contrast, typically requires reduced locomotion. Another long-standing concept is "rest and digest", a hypolocomotive response to calorie intake, thought to facilitate digestion and storage of energy after eating. Here, we note that the classical seek➔ingest➔rest behavioural sequence is not evolutionarily advantageous for all ingested nutrients. Our limited stomach capacity should be invested wisely, rather than spent on the first available nutrient. This is because nutrients are not simply calories: some nutrients are more essential for survival than others. Thus, a key choice that needs to be made soon after ingestion: to eat more and rest, or to terminate eating and search for better food. We offer a perspective on recent work suggesting how nutrient-specific neural responses shape this choice. Specifically, the hypothalamic hypocretin/orexin neurons (HONs) - cells that promote hyperlocomotive explorative behaviours - are rapidly and differentially modulated by different ingested macronutrients. Dietary non-essential (but not essential) amino acids activate HONs, while glucose depresses HONs. This nutrient-specific HON modulation engages distinct reflex arcs, seek➔ingest➔seek and seek➔ingest➔rest, respectively. We propose that these nutri-neural reflexes evolved to facilitate optimal nutrition despite the limitations of our body.

The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning.

Prediction error (PE) is the mismatch between a prior expectation and reality, and it lies at the core of associative learning about aversive and appetitive stimuli. Human studies on fear learning have linked the amygdala to aversive PEs. In contrast, the relationship between the amygdala and PE in appetitive settings and stimuli, unlike those that induce fear, has received less research attention. Animal studies show that the amygdala is a functionally heterogeneous structure. Nevertheless, the role of the amygdala nuclei in PE signaling remains unknown in humans. To clarify the role of two subdivisions of the human amygdala, the centromedial amygdala (CMA) and basolateral amygdala (BLA), in appetitive and aversive PE signaling, we used gustatory pavlovian learning involving eating-related naturalistic outcomes. Thirty-eight right-handed individuals (19 females) participated in the study. We found that surprise with neutral feedback when a reward is expected triggers activity within the left and right CMA. When an aversive outcome is expected, surprise with neutral feedback triggers activity only within the left CMA. Notably, the BLA was not activated by those conditions. Thus, the CMA engages in negative PE signaling during appetitive and aversive gustatory pavlovian learning, whereas the BLA is not critical for this process. In addition, PE-related activity within the left CMA during aversive learning is negatively correlated with neuroticism and positively correlated with extraversion. The findings indicate the importance of the CMA in gustatory learning when the value of outcomes changes and have implications for understanding psychological conditions that manifest perturbed processing of negative PEs.SIGNIFICANCE STATEMENT A discrepancy between a prediction and an actual outcome (PE) plays a crucial role in learning. Learning improves when an outcome is more significant than expected (positive PE) and worsens when it is smaller than expected (negative PE). We found that the negative PE during appetitive and aversive taste learning is associated with increased activity of the CMA, which suggests that the CMA controls taste learning. Our findings may have implications for understanding psychological states associated with deficient learning from negative PEs, such as obesity and addictive behaviors.

Modulation of aversive value coding in the vertebrate and invertebrate brain.

Avoiding potentially dangerous situations is key for the survival of any organism. Throughout life, animals learn to avoid environments, stimuli or actions that can lead to bodily harm. While the neural bases for appetitive learning, evaluation and value-based decision-making have received much attention, recent studies have revealed more complex computations for aversive signals during learning and decision-making than previously thought. Furthermore, previous experience, internal state and systems level appetitive-aversive interactions seem crucial for learning specific aversive value signals and making appropriate choices. The emergence of novel methodologies (computation analysis coupled with large-scale neuronal recordings, neuronal manipulations at unprecedented resolution offered by genetics, viral strategies and connectomics) has helped to provide novel circuit-based models for aversive (and appetitive) valuation. In this review, we focus on recent vertebrate and invertebrate studies yielding strong evidence that aversive value information can be computed by a multitude of interacting brain regions, and that past experience can modulate future aversive learning and therefore influence value-based decisions.

The relationship between sleep and appetitive conditioning: A systematic review and meta-analysis.

This systematic review and meta-analysis (PROSPERO registration animal/human studies: CRD42021234793/CRD42021234790) examined the relationship between sleep and appetitive conditioning. Inclusion criteria included: a) appetitive conditioning paradigm; b) measure of conditioning; c) sleep measurement and/or sleep loss; d) human and/etor non-human animal samples; and e) written in English. Searches of seven databases returned 3777 publications. The final sample consisted of 42 studies using primarily animal samples and involving food- and drug-related conditioning tasks. We found sleep loss disrupted appetitive conditioning of food rewards (p < 0.001) but potentiated appetitive conditioning of drug rewards (p < 0.001). Furthermore, sleep loss negatively impacted extinction learning irrespective of the reward type. Post-learning sleep was associated with increases in REM sleep (p = 0.02). Findings suggest sleep loss potentiates the impact of psychoactive substances in a manner likely to produce an increased risk of problematic substance use. In obese/overweight populations, sleep loss may be associated with deficits in the conditioning and extinction of reward-related behaviours. Further research should assess the relationship between sleep and appetitive conditioning in humans.

Complementary Feeding and Child Appetitive Traits in a Sample of Hispanic Mother-Child Dyads.

BACKGROUND: Complementary feeding practices may contribute to toddler eating practices that affect weight outcomes. Studies are needed to understand the relationship between complementary feeding practices and toddler dietary self-regulation. OBJECTIVE: This study tests the hypothesis that earlier complementary food introduction predicts toddler food responsiveness and emotional overeating (ie, tendency to overeat in response to food cues and emotions, respectively), and considers whether introduction of certain foods better predict toddler dietary self-regulation. DESIGN: This study is a secondary analysis of data from a parent longitudinal birth cohort study on early growth/development among Hispanic mother-infant dyads. PARTICIPANTS/SETTING: The analytic sample included 174 mother-child dyads recruited from maternity clinics affiliated with the University of Southern California in Los Angeles County. Recruitment and data collection were ongoing from July 2016 to April 2020. At 1-, 6-, 12-, and 24-months postpartum, mothers reported exclusive breastfeeding duration and age of complementary food introduction via questionnaire. MAIN OUTCOME MEASURES: Child food responsiveness and emotional overeating scores calculated from the Child Eating Behavior Questionnaire at 12 and 24 months of age. STATISTICAL ANALYSES PERFORMED: Separate linear mixed models with repeated measures were used to examine associations between age of complementary food introduction as a predictor of child food responsiveness or emotional overeating, controlling for infant sex, birth body mass index z score, duration of exclusive breastfeeding, and mother's body mass index. RESULTS: In separate models, delaying complementary food introduction by 1 month was associated with a 6% reduction in food responsiveness (P = 0.007) and a 5% reduction in emotional overeating scores (P = 0.013). Fifty-eight unique combinations of complementary foods introduced first were found, precluding analyses to examine whether specific combinations were related to eating behavior outcomes due to sample size limitations. CONCLUSIONS: Earlier complementary feeding was associated with higher food responsiveness and emotional overeating scores among Hispanic children. Future studies in larger samples are needed to characterize patterns of complementary food introduction and their influence on child self-regulation.

Stress effects on memory retrieval of aversive and appetitive instrumental counterconditioning in men.

Extinction training creates a second inhibitory memory trace and effectively reduces conditioned responding. However, acute stress inhibits the retrieval of this extinction memory trace. It is not known whether this also applies to other forms of associative learning such as instrumental counterconditioning, where previously learned associations are reversed and paired with the opposite valence. Therefore, the current preregistered study investigates whether stress decreases the retrieval of instrumental counterconditioning memories with aversive and appetitive consequences. Fifty-two healthy men were randomly assigned to either a stress or control group and took part in a two-day instrumental learning paradigm. During a first phase, participants learned that pressing specific buttons in response to the presentation of four neutral stimuli either leads to gaining or losing money. During a second phase, two stimuli reversed their contingencies (counterconditioning). One day later, participants were exposed to acute stress or a control condition prior to the same task, which no longer included feedback about gains or losses. Stressed participants showed more approach behavior towards appetitive and less avoidance behavior towards aversive stimuli as compared to non-stressed participants. Our findings indicate that stress effects on memory retrieval differ depending on the associative learning approach in men. These differences might be related to stress effects on decision making and different motivational systems involved.