Sex differences in the reward value of familiar mates in prairie voles

The rewarding properties of social interactions facilitate relationship formation and maintenance. Prairie voles are one of the few laboratory species that form selective relationships, manifested as "partner preferences" for familiar partners versus strangers. While both sexes exhibit strong partner preferences, this similarity in outward behavior likely results from sex-specific neurobiological mechanisms. We recently used operant conditioning to demonstrate that females work harder for access to a familiar versus unfamiliar conspecific of either sex, while males worked equally hard for access to any female, indicating a key sex difference in social motivation. As tests were performed with one social target at a time, males might have experienced a ceiling effect, and familiar females might be more relatively rewarding in a choice scenario. Here we performed a social choice operant task in which voles could repeatedly lever-press to gain temporary access to either the chamber containing their mate or one containing a novel opposite-sex vole. Females worked hardest to access their mate, while males pressed at similar rates for either female. Individual male behavior was heterogeneous, congruent with multiple mating strategies in the wild. Voles exhibited preferences for favorable over unfavorable environments in a non-social operant task, indicating that lack of social preference does not reflect lack of discrimination between chambers. Oxytocin receptor genotype at the intronic SNP NT213739 replicated a prior association with stranger-directed aggression within the test. These findings suggest that convergent preference behavior in male and female voles results from sex-divergent pathways, particularly in the realm of social motivation.

Increased Behavioral Sensitivity to Repeated Experiences of Punishment in Children With ADHD: Experimental Studies Using the Matching Law

Background: Research on altered motivational processes in ADHD has focused on reward. The sensitivity of children with ADHD to punishment has received limited attention. We evaluated the effects of punishment on the behavioral allocation of children with and without ADHD from the United States, New Zealand, and Japan, applying the generalized matching law. Methods: Participants in two studies (Furukawa et al., 2017, 2019) were 210 English-speaking (145 ADHD) and 93 Japanese-speaking (34 ADHD) children. They completed an operant task in which they chose between playing two simultaneously available games. Rewards became available every 10 seconds on average, arranged equally across the two games. Responses on one game were punished four times as often as responses on the other. The asymmetrical punishment schedules should bias responding to the less punished alternative. Results: Compared with controls, children with ADHD from both samples allocated significantly more responses to the less frequently punished game, suggesting greater behavioral sensitivity to punishment. For these children, the bias toward the less punished alternative increased with time on task. Avoiding the more punished game resulted in missed reward opportunities and reduced earnings. English-speaking controls showed some preference for the less punished game. The behavior of Japanese controls was not significantly influenced by the frequency of punishment, despite slowed response times after punished trials and immediate shifts away from the punished game, indicating awareness of punishment. Conclusion: Punishment exerted greater control over the behavior of children with ADHD, regardless of their cultural background. This may be a common characteristic of the disorder. Avoidance of punishment led to poorer task performance. Caution is required in the use of punishment, especially with children with ADHD. The group difference in punishment sensitivity was more pronounced in the Japanese sample; this may create a negative halo effect for children with ADHD in this culture.

Rest Is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

Maladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. In the paradigm, flies walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, they receive a sucrose reward at the end of the hallway. Only flies that rest early in training learn the reward contingency normally. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced sleep does not promote learning, indicating that sleep itself is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning-impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.

Whole brain dynamics during optogenetic self-stimulation of the medial prefrontal cortex in mice

Intracranial self-stimulation, in which an animal performs an operant response to receive regional brain electrical stimulation, is a widely used procedure to study motivated behavior. While local neuronal activity has long been measured immediately before or after the operant, imaging the whole brain in real-time remains a challenge. Herein we report a method that permits functional MRI (fMRI) of brain dynamics while mice are cued to perform an operant task: licking a spout to receive optogenetic stimulation to the medial prefrontal cortex (MPFC) during a cue ON, but not cue OFF. Licking during cue ON results in activation of a widely distributed network consistent with underlying MPFC projections, while licking during cue OFF (without optogenetic stimulation) leads to negative fMRI signal in brain regions involved in acute extinction. Noninvasive whole brain readout combined with circuit-specific neuromodulation opens an avenue for investigating adaptive behavior in both healthy and disease models.

Effects of maternal deprivation and complex housing on pro-social behavior in rats: An automated, operant task examining motivation to liberate a trapped conspecific

Early life environment influences the development of various aspects of social behavior, particularly during sensitive developmental periods. Here, we aimed to study how challenges in the early postnatal period or (early) adolescence affect pro-social behavior. To this end, we adapted an existing paw operated liberation task to an automated operant task, to measure motivation (by progressively increasing required lever pressing) to liberate a trapped conspecific. Liberation of the trapped rat resulted either in social contact, or in liberation into a separate compartment. Additionally, a condition was tested in which both rats could freely move in two separate compartments and lever pressing resulted in social contact. When partners were not trapped, rats were more motivated to press the lever for opening the door than in either of the trapped configurations. Contrary to our expectation, the trapped configuration resulted in a reduced motivation to act. Early postnatal stress (24h maternal deprivation on postnatal day 3) did not affect behavior in the liberation task. However, rearing rats from early adolescence onwards in complex housing conditions (Marlau cages) reduced the motivation to door opening, both in the trapped and freely moving conditions, while motivation for a sucrose reward was not affected.

Rest is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

ABSTRACTMaladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. Flies of both sexes walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, sucrose is presented at the end of the hallway. Only flies that rest during training show evidence of learning the reward contingency. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced rest does not promote learning, indicating that rest is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.SIGNIFICANCE STATEMENTOperant conditioning and mental health are deeply intertwined: maladaptive conditioning contributes to many pathologies, while therapeutic operant conditioning is a frequently used tool in talk therapy. Unlike drug interventions which target molecules or mechanisms, it is not known how operant conditioning changes the brain to promote wellness or distress. To gain mechanistic insight into how this form of learning works, we developed a novel operant training task for the fruit fly Drosophila melanogaster. We made three key discoveries. First, flies are able to learn an operant task to find food reward. Second, rest during training is necessary for learning. Third, the dunce gene is necessary for both classical and operant conditioning in flies, indicating that they may share molecular mechanisms.

Masking the Detection of Taste Stimuli in Rats: NaCl and Sucrose

While psychophysical and neurophysiological assessments of taste sensitivity to single chemical compounds have revealed some fundamental properties of gustatory processing, taste stimuli are rarely ingested in isolation. Arguably, the gustatory system was adapted to identify and report the presence of numerous chemicals ingested concurrently. To begin systematically exploring the detectability of a target stimulus in a background in rodents, we used a gustometer to train rats in a 2-response operant task to detect either NaCl (n = 8) or sucrose (n = 8) dissolved in water, and then tested the sensitivity of rats to the trained NaCl stimulus dissolved in a sucrose masker (0.3, 0.6, or 1.0 M, tested consecutively) versus sucrose, or the trained sucrose stimulus dissolved in a NaCl masker (0.04, 0.2, or 0.4 M) versus NaCl. Detection thresholds (EC50 values) were determined for the target stimulus dissolved in each concentration of the masker. Except for 0.04 M NaCl, all masker concentrations tested increased the target stimulus EC50. Target stimulus detectability decreased systematically as masker concentrations increased. The shift in liminal sensitivity for either target was similar when the threshold for the masker was considered. At least for these prototypical stimuli, it appears that the attenuating impact of a masker on the detection of a target stimulus depends on sensitivity to the masking stimulus. Further study will be required to generalize these results and extend them to more complex maskers, and to discern neural circuits involved in the detection of specific taste signals in the context of noisy backgrounds.

Pair housing makes calves more optimistic

Individual housing of dairy calves is common farm practice, but has negative effects on calf welfare. A compromise between practice and welfare may be housing calves in pairs. We compared learning performances and affective states as assessed in a judgement bias task of individually housed and pair-housed calves. Twenty-two calves from each housing treatment were trained on a spatial Go/No-go task with active trial initiation to discriminate between the location of a teat-bucket signalling either reward (positive location) or non-reward (negative location). We compared the number of trials to learn the operant task (OT) for the trial initiation and to finish the subsequent discrimination task (DT). Ten pair-housed and ten individually housed calves were then tested for their responses to ambiguous stimuli positioned in-between the positive and negative locations. Housing did not affect learning speed (OT: F1,35 = 0.39, P = 0.54; DT: F1,19 = 0.15, P = 0.70), but pair-housed calves responded more positively to ambiguous cues than individually housed calves (χ21 = 6.79, P = 0.009), indicating more positive affective states. This is the first study to demonstrate that pair housing improves the affective aspect of calf welfare when compared to individual housing.