Biology subjects

Rodriguez Parkitna, J.

Publications and source records attributed to Rodriguez Parkitna, J..

8 recordsLinked to original sources

bioRxiv2026

The effect of preproenkephalin gene deletion on heart function in mice

Enkephalins, the endogenous ligands of the - and {delta}-opioid receptors, are abundantly expressed in the nervous system and peripheral organs, including the heart. Accumulating evidence suggests that they participate in cardiac development and act as autocrine and paracrine modulators of heart activity. Here, we investigate the role of enkephalins in cardiac physiology using a newly generated mouse strain with a complete ablation of the preproenkephalin (Penk) gene. We find that, although adult mutant mice weighed less, the mutation caused no apparent changes in behavioral phenotype, no increase in anxiety-like behaviors, and only a mild reduction in locomotor activity. There was no effect of Penk deletion on heart weight or size. A comprehensive analysis of left ventricular function using MRI revealed normal basal cardiac performance, except for a significant reduction in the peak fill and ejection rates. There were no significant effects of Penk deletion on left ventricular function after {beta}1-adrenergic stimulation with dobutamine. At the same time, we observed the expected significant differences in heart size and function between male and female mice. In conclusion, our data show that enkephalins are not essential for normal heart development and have a moderate impact on adult heart function under basal conditions.

neuroscience↗

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

The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

Dopamine signalling in the motor cortex is crucial for motor skill learning. Here we resolve the spatiotemporal dopamine dynamics and the activity of local dopaminoceptive circuits during the formation and execution of motor skills. We trained head-fixed mice to perform skilled forelimb movements with a joystick to collect water rewards, while simultaneously monitoring dopamine release and calcium dynamics in the forelimb area of motor cortex. We found that dopamine release events and calcium transients were temporally linked to joystick movements and reward consumption. Dopamine dynamics and population level activity of dopamine-receptive neurons scaled with the vigor of forelimb movements and tracked the relationship between actions and their consequences. Optogenetic photoinhibition of cortical dopaminoceptive circuits reduced the number of rewarded joystick movements. Our findings show how phasic dopamine signals in the motor cortex facilitate reinforcement motor learning of skilled behavior.

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

Effects of L-DOPA on gene expression in the frontal cortex of rats with unilateral lesion of midbrain dopaminergic neurons

The development of Parkinsons disease (PD) causes dysfunction of the frontal cortex, which contributes to hallmark motor symptoms and is regarded as one of the primary causes of the affective and cognitive impairments observed in PD. Treatment with L-DOPA alleviates motor symptoms but has mixed efficacy in restoring normal cognitive functions, which is further complicated by the psychoactive effects of the drug. In this study, we investigated how L-DOPA affects gene expression in the frontal cortex in an animal model of unilateral PD. We performed an RNA-seq analysis of gene expression in the frontal cortex of rats with 6-hydroxydopamine (6-OHDA)-induced unilateral dopaminergic lesion that were treated with L-3,4-dihydroxyphenylalanine (L-DOPA), for 2 weeks. We used analysis of variance to identify differentially expressed genes and found 48 genes with significantly altered transcript abundance after L-DOPA treatment. We also performed a weighted gene coexpression network analysis (WGCNA), which resulted in the detection of 5 modules consisting of genes with similar expression patterns. The analyses led to three primary observations. First, the changes in gene expression induced by L-DOPA were bilateral, although only one hemisphere was lesioned. Second, the changes were not restricted to neurons but also appeared to emerge in immune or endothelial cells. Finally, comparisons with databases of drug-induced gene expression signatures revealed multiple nonspecific effects, which indicates that a part of the observed response is a common pattern activated by multiple types of pharmaceuticals in different target tissues. Taken together, our results identify cellular mechanisms in the frontal cortex that are involved in the response to L-DOPA treatment.

neuroscience↗

bioRxiv2019

Time elapsed between choices in a probabilistic task correlates with repeating the same decision.

Reinforcement learning causes an action that yields a positive outcome more likely to be taken in the future. Here, we investigate how the time elapsed from an action affects subsequent decisions. Groups of C57BL6/J mice were housed in IntelliCages with access to water and chow ad libitum; they also had access to bottles with a reward: saccharin solution, alcohol or a mixture of the two. The probability of receiving a reward in two of the cage corners changed between 0.9 and 0.3 every 48 h over a period of ~33 days. As expected, in most animals, the odds of repeating a corner choice were increased if that choice was previously rewarded. Interestingly, the time elapsed from the previous choice also influenced the probability of repeating the choice, and this effect was independent of previous outcome. Behavioral data were fitted to a series of reinforcement learning models. Best fits were achieved when the reward prediction update was coupled with separate learning rates from positive and negative outcomes and additionally a "fictitious" update of the expected value of the nonselected choice. Additional inclusion of a time-dependent decay of the expected values improved the fit marginally in some cases.

animal behavior and cognition↗

bioRxiv2018

Ablation of NMDA receptors in dopamine neurons disrupts attribution of incentive salience to reward-paired stimuli

Midbrain dopamine (DA) neurons play a crucial role in the formation of conditioned associations between environmental cues and appetitive events. Activation of N-methyl-D-aspartate (NMDA) receptors is a key mechanism responsible for the generation of conditioned responses of DA neurons to reward cues. Here, we tested the effects of the cell type-specific inactivation of NMDA receptors in DA neurons in adult mice on stimulus-reward learning. Animals were trained in a Pavlovian learning paradigm in which they had to learn the predictive value of two conditioned stimuli, one of which (CS+) was paired with the delivery of a water reward. Over the course of conditioning, mutant mice learned that the CS+ predicted reward availability, and they approached the reward receptacle more frequently during CS+ trials than CS- trials. However, conditioned responses to the CS+ were weaker in the mutant mice, possibly indicating that they did not attribute incentive salience to the CS+. To further assess whether the attribution of incentive salience was impaired by the mutation, animals were tested in a conditioned reinforcement test. The test revealed that mutant mice made fewer instrumental responses paired with CS+ presentation, confirming that the CS+ had a weaker incentive value. Taken together, these results indicate that reward prediction learning does occur in the absence of NMDA receptors in DA neurons, but the ability of reward-paired cues to invigorate and reinforce behavior is lost.

animal behavior and cognition↗