Biology subjects

Harda, Z.

Publications and source records attributed to Harda, Z..

10 recordsLinked to original sources

bioRxiv2025

Individual and social contributions to learning of mice in Intellicages: the general framework and mean field theory

Reinforcement learning enables the adaptation of behaviors to changes in the environment. Models of reinforcement learning based on using previous experience to guide future choices enable balancing exploitation of opportunities and exploring the options and provide accurate predictions of animal behavior in simple instrumental tasks. However, they fail to account for the critical advantage we and other animals have, namely the ability not only to learn from our own choices but also from observing the outcomes of choices made by others. Here, we propose a new conceptual, analytical, and computational framework combining point processes with reinforcement learning models for the description, analysis and modeling of individual and group effects of mice learning reward placement. We show that marked point processes provide a natural language to describe behavior of group housed mice. We show how different reinforcement models of the behavior, including group effects, can be studied effectively in this framework, using example experiments. With this framework we show that the group effects (peer pressure) are twice stronger than individual learning.

animal behavior and cognition↗

bioRxiv2025

Modeling social influence as a reinforcer reveals varying individual learning strategies and the group's structure

In a social context, knowledge can be gained through observation and imitation, but in a numerous group, social influence can also be contradictory and confusing. The mechanisms of social learning in groups have not been fully characterized, partly due to the lack of adequate mathematical description. Using the known reinforcing property of social influence we introduce a reinforcement learning model which can account for social effects at the group and individual level. We use it to reveal pairwise influence relations and the overall learning strategies in a reversal learning task applied to a cohort of mice housed in an Intellicage. Animals make an efficient use of social influence when the goal of the group agrees with their own, but switch to an individual learning scheme when these goals are misaligned. They also exhibit varied decision rules depending on their own motivational state, and a selectivity in assimilating social information depending on the state of their conspecifics.

animal behavior and cognition↗

bioRxiv2025

Decreased social, drug, and food reward sensitivity in adolescent mice

Adolescence shapes adaptive adult behaviors. Most studies compare single adolescent and adult age groups using only one type of reward, limiting insight into developmental trajectories underlying behavioral change. Here, we investigated how social, cocaine, and palatable food rewards become associated with environmental contexts in female and male C57BL/6 mice across early- (pubertal onset), mid- (peripubertal phase), and late- (sexual maturity) adolescence, compared to adults. Using the conditioned place preference (CPP) task, we found that generally all rewards induced place preference for the reward-associated context, with only minor effects of sex. In contrast, age significantly influenced CPP expression. Adolescent mice exhibited a significantly reduced CPP compared to adults in palatable food and social CPP paradigms, evident in both decreased mean conditioned context preference and lower proportion of animals that developed a preference after conditioning. Cocaine CPP was not significantly affected by age. Direct comparisons across CPP task outcomes further confirmed that age, rather than reward type or sex, was the primary factor influencing the magnitude of CPP. Specifically, mid- and late-adolescent mice showed reduced mean reward CPP, and mid-adolescents were less likely to express a reward preference relative to adults. Based on the behavioral analyses, we conclude that the lower expression of preference for a conditioned context in adolescent animals is due to developmental changes in reward sensitivity, rather than deficits in learning or higher novelty-seeking behavior.

animal behavior and cognition↗

bioRxiv2025

Changes in social reward across adolescence in male mice

In humans, adolescence is a time of dynamic behavioral and emotional changes, including a transient decrease in affect associated with being among family members. It is not clear if a similar change occurs in rodent species used to model human psychiatric disorders. Here, we investigated the developmental profile of the rewarding value of interactions with siblings across adolescence in male mice, using the social conditioned place preference task. We found that the reward value of social interactions followed a similar course to that in humans: high in early adolescence, it decreased in mid-adolescence and returned to the initial level in late adolescence. The observed change was specific to social interaction, as no age-dependent changes in preference for cocaine-conditioned context were detected. Taken together, these data show similarities between mice and humans in developmental changes in sensitivity to the rewarding effects of interactions with familiar kin.

neuroscience↗

bioRxiv2023

Molecular fingerprints in the hippocampus of alcohol seeking during withdrawal

Alcohol use disorder (AUD) is characterized by excessive alcohol seeking and use. Here, we investigated the molecular correlates of impaired extinction of alcohol seeking using a multidimentional mouse model of AUD. We distinguished AUD-prone and AUD-resistant mice, based on the presence of [≥] 2 or < 2 criteria of AUD and utilized RNA sequencing to identify genes that were differentially expressed in the hippocampus and amygdala of mice meeting [≥] 2 or < 2 criteria, as these brain regions are implicated in alcohol motivation, seeking, consumption and the cognitive inflexibility characteristic of AUD. Our findings revealed dysregulation of the genes associated with the actin cytoskeleton, including actin binding molecule cofilin, and impaired synaptic transmission in the hippocampi of mice meeting [≥] 2 criteria. Overexpression of cofilin in the polymorphic layer of the dentate gyrus (PoDG) inhibited ML-DG synapses, increased motivation to seek alcohol and impaired extinction of alcohol seeking, resembling the phenotype observed in mice meeting [≥] 2 criteria. Overall, our study uncovers a novel mechanism linking increased hippocampal cofilin expression with the AUD phenotype. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/554622v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@14b3fadorg.highwire.dtl.DTLVardef@141b1fdorg.highwire.dtl.DTLVardef@c82b8org.highwire.dtl.DTLVardef@15a16ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2023

Mu-opioid receptor-dependent changes in social reward across adolescence in mice

RationaleSocial behaviors undergo dramatic changes during adolescence, enabling the development of adult social abilities. These changes are intricately linked to the development of the brain reward system and the activity of endogenous opioid signaling. However, the involvement of the opioid system in the development of social behaviors still raises more questions than answers. ObjectivesHere, we investigated the role of the endogenous opioid system in the rewarding effects of social contact in early and late adolescent male mice. MethodsSocial reward was assessed using the social conditioned place preference task in early adolescent (~34 days old) and late adolescent (~41 days old) male mice that received a single dose of the selective opioid receptor antagonists cyprodime (1 mg/kg, i.p.), naltrindole (1 mg/kg, i.p.) or norbinaltorphimine (10 mg/kg, i.p.) before the preference posttest. ResultsThe administration of cyprodime or naltrindole before the posttest significantly increased the preference for the social-conditioned context in early but not late adolescent mice. In contrast, pretreatment with norbinaltorphimine had no effect on context preference. ConclusionsOur findings support a modified version of the state-dependent mu-opioid receptor model of social behavior, where the effects of opioid ligands are not reversed during development but rather weaken or disappear with age. Furthermore, the results indicate that interactions with siblings in early adolescent mice are motivated by negative reinforcement, whereas those in late adolescence are motivated by positive reinforcement.

neuroscience↗

bioRxiv2023

Nonmotor symptoms associated with progressive loss of dopaminergic neurons in a mouse model of Parkinson's disease

Parkinsons disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse nonmotor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the nonmotor symptoms of PD in a mouse model of the disease (the TIF-IADATCreERT2 strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the step cadence and sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent nonmotor symptoms that emerge in the early stages of dopaminergic neuron degeneration.

neuroscience↗

bioRxiv2022

Prosocial behavior in adult mice is sex-dependent

Prosocial behavior, defined as voluntary behavior intended to benefit another, has long been regarded as a primarily human characteristic. In recent years, it was reported that laboratory animals also favor prosocial choices in various experimental paradigms, thus demonstrating that prosocial behaviors are evolutionarily conserved. Here, we investigated prosocial choices in adult male and female C57BL/6 laboratory mice in a task where a subject mouse is equally rewarded for entering any of the two compartments of the experimental cage, but only entering of the compartment designated as "prosocial" rewards an interaction partner. In parallel we have also assessed two traits that are regarded as closely related to prosociality: sensitivity to social reward and the ability to recognize the affective state of another individual. We find that female, but not male, mice increased frequency of prosocial choices from pretest to test. At the same time, both sexes showed similar rewarding effects of social contact in the conditioned place preference test, and similarly, there was no effect of sex on affective state discrimination measured as the preference for interaction with a hungry or relieved mouse over a neutral animal. These observations bring interesting parallels to differences between sexes observed in humans, and are in line with reported higher propensity for prosocial behavior in human females, but differ with regard to sensitivity to social stimuli in males.

animal behavior and cognition↗

bioRxiv2022

A robust method for measuring social reward in adult mice

Social interactions can be and often are rewarding. The effect of social contact strongly depends on circumstances, and the reward may be driven by varied motivational processes, ranging from parental or affiliative behaviors to investigation or aggression. Reward associated with nonreproductive interactions in rodents is measured using the social conditioned place preference (sCPP) paradigm, where a change in preference for an initially neutral context confirms reinforcing effects of social contact. Here, we revised the sCPP method and reexamined social reward in adult female mice. Contrary to earlier studies, we found that robust rewarding effects of social contact could be detected in adult (14-week-old) female C57BL/6 mice when the sCPP task was refined to remove confounding factors. Strikingly, the rewarding effects of social interaction were only observed among female siblings who remained together from birth. Contact with same-age nonsiblings was not rewarding even after 8 weeks of cohousing. Other factors critical for the social reward effect in the sCPP paradigm included the number of conditioning sessions and the inherent preference for contextual cues. Thus, we show that social interaction is rewarding in adult female mice, but this effect strictly depends on the familiarity of the interaction partners. Furthermore, by identifying confounding factors, we provide a behavioral model to study the mechanisms underlying the rewarding effects of nonreproductive social interaction in adult mice.

animal behavior and cognition↗

bioRxiv2020

Loss of mu and delta opioid receptors on neurons expressing dopamine receptor D1 has no effect on reward sensitivity

Opioid signaling controls the activity of the brains reward system. It is involved in signaling the hedonic effects of rewards and also has essential roles in reinforcement and motivational processes. Here, we focused on opioid signaling through mu and delta receptors on dopaminoceptive neurons and evaluated the role these receptors play in reward-driven behaviors. We generated a genetically modified mouse with selective double knockdown of mu and delta opioid receptors in neurons expressing dopamine receptor D1. Selective expression of the transgene was confirmed using immunostaining. Knockdown was validated by measuring the effects of selective opioid receptor agonists on neuronal membrane currents using whole-cell patch clamp recordings. We found that in the nucleus accumbens of control mice, the majority of dopamine receptor D1-expressing neurons were sensitive to a mu or delta opioid agonist. In mutant mice, the response to the delta receptor agonist was blocked, while the effects of the mu agonist were strongly attenuated. Behaviorally, the mice had no obvious impairments. The mutation did not affect sensitivity to the rewarding effects of morphine injections or social contact and had no effect on preference for sweet taste. Knockdown had a moderate effect on motor activity in some of the tests performed, but this effect did not reach statistical significance. Thus, we found that knocking down mu and delta receptors on dopamine receptor D1-expressing cells does not appreciably affect reward-driven behaviors. Highlights- It is well accepted that opioid signaling controls the brains reward system - We generated mutant mice with mu and delta receptor knockdown in D1 neurons - Knockdown made dopaminoceptive neurons insensitive to mu and delta opioid receptor agonists - The mutation did not cause obvious behavioral impairments - The loss of mu and delta receptors on D1 neurons does not affect reward sensitivity

neuroscience↗