Interval timing is involved in a variety of cognitive behaviors such as associative learning and decision-making. While it has been shown that time estimation is adaptive to the temporal context, it remains unclear how interval timing behavior is influenced by recent trial history. Here we found that, in mice trained to perform a licking-based interval timing task, a decrease of inter-reinforcement interval in the previous trial rapidly shifted the time of anticipatory licking earlier. Optogenetic inactivation of the anterior lateral motor cortex (ALM), but not the medial prefrontal cortex, for a short time before reward delivery caused a decrease in the peak time of anticipatory licking in the next trial. Electrophysiological recordings from the ALM showed that the response profiles preceded by short and long inter-reinforcement intervals exhibited task-engagement-dependent temporal scaling. Thus, interval timing is adaptive to recent experience of the temporal interval, and ALM activity during time estimation reflects recent experience of interval.
Animals ; Mice ; Reward ; Time Factors ; Cognition ; Learning ; Decision Making ; Reinforcement, Psychology

BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. METHODS: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. RESULTS: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. CONCLUSIONS A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Humans ; Mice ; Animals ; Psilocybin/metabolism* ; Fear ; Extinction, Psychological ; Brain-Derived Neurotrophic Factor/metabolism* ; Bromodeoxyuridine/pharmacology* ; Hippocampus/metabolism* ; Neuronal Plasticity ; TOR Serine-Threonine Kinases/metabolism*

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

Recent work in decision neuroscience suggests that visual saliency can interact with reward-based choice, and the lateral intraparietal cortex (LIP) is implicated in this process. In this study, we recorded from LIP neurons while monkeys performed a two alternative choice task in which the reward and luminance associated with each offer were varied independently. We discovered that the animal's choice was dictated by the reward amount while the luminance had a marginal effect. In the LIP, neuronal activity corresponded well with the animal's choice pattern, in that a majority of reward-modulated neurons encoded the reward amount in the neuron's preferred hemifield with a positive slope. In contrast, compared to their responses to low luminance, an approximately equal proportion of luminance-sensitive neurons responded to high luminance with increased or decreased activity, leading to a much weaker population-level response. Meanwhile, in the non-preferred hemifield, the strength of encoding for reward amount and luminance was positively correlated, suggesting the integration of these two factors in the LIP. Moreover, neurons encoding reward and luminance were homogeneously distributed along the anterior-posterior axis of the LIP. Overall, our study provides further evidence supporting the neural instantiation of a priority map in the LIP in reward-based decisions.
Animals ; Macaca mulatta/physiology* ; Parietal Lobe ; Neurons/physiology* ; Saccades ; Reward ; Photic Stimulation

Objective: To investigate the occupational stress status of air traffic controllers (ATC) and analyze its influencing factors. Methods: By using cluster sampling method, 457 ATCs in an air traffic management bureau were selected as the investigation objects. The job content questionnaire (JCQ) and the effort reward imbalance questionnaire (ERI) were used to measure work requirements independent imbalance type and ERI type occupational stress separately and analyze the influencing factors. Results: Of the 457 ATCs, 81.84% (374/457) ATGs had work requirements independent imbalance type of occupational stress and 84.46% (386/457) ATGs had ERI type occupational stress. Univariate analysis showed that the factors of marital status, degree of education, age, length of service, title, job post, family monthly income, views on regular training, occurrence of emergency or unsafe events in last month and monthly night shift frequency had various degrees of influence on the different factor scores of JCQ and ERI (P<0.01) . Logistic regression analysis showed that the level of JCQ type occupational stress of ATCs with junior titles and probationers was higher than those of intermediate/senior titles (P=0.000, 0.000) ; The ERI type occupational stress of probationers and junior titles ATCs was lower than those with intermediate/senior titles (P=0.000) . The ERI and JCQ type occupational stress level of tower post ATCs was higher than that of other two job post ATCs (P=0.001, 0.000, 0.000, 0.000) . The ATCs considering regular training had more disadvantages than advantages showed lower ERI type occupational stress level than those considering more advantages than disadvantages (P=0.000) . The ERI type occupational stress level of ATCs who experienced emergency or unsafe events in last month was higher than those who didn't (P=0.007) . Conclusion: A large proportion of ATCs had occupational stress. Management should adjust its policies and pay were attention to occupational stress of ATLs.
Cross-Sectional Studies ; Employment ; Humans ; Job Satisfaction ; Occupational Stress/epidemiology* ; Reward ; Stress, Psychological/epidemiology* ; Surveys and Questionnaires

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
Animals ; Dopaminergic Neurons/physiology* ; GABAergic Neurons/physiology* ; Mice ; Nucleus Accumbens/metabolism* ; Reward ; Ventral Tegmental Area/metabolism*

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the "third-party framing effect". In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as "harming others" in one condition and "not helping others" in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.
Empathy ; Female ; Gyrus Cinguli ; Humans ; Neuroimaging ; Pain ; Punishment/psychology*

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Animals ; Brain ; Cocaine ; Conditioning, Operant ; Extinction, Psychological ; Lipidomics ; Male ; Mice ; Simvastatin/therapeutic use*

Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABA receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.
Animals ; Baclofen ; administration & dosage ; Conditioning, Classical ; GABA-B Receptor Agonists ; administration & dosage ; Locomotion ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; Morphine ; Nucleus Accumbens ; drug effects ; Opioid-Related Disorders ; Reward

RESULTS: A positive significant correlation was observed between the BMI groups and the negative emotions, negative situations, and negative total scores of EMAQ (P < 0.01). The regression results on negative subscales showed that a one unit increase in BMI resulted in a 0.293 unit increase in negative situations scores, a 0.626 unit increase in negative emotions scores, and a 0.919 unit increase in negative total EMAQ scores. When the BMI groups and PEMS subscale scores were examined, a significant relationship was found in the social motives, rewarding, and conformity subscales (P < 0.01). A one unit increase in BMI increased the coping motives scores by 0.077 units.CONCLUSIONS: The emotional states have a significant effect on the eating behavior. On the other hand, an increase in eating attacks was observed, particularly in people who were under the effect of a negative emotion or situation. Nevertheless, there were some limitations of the study in terms of quantitative determination of the effects of this eating behavior depending on the BMI.]]>
Adult ; Appetite ; Data Collection ; Eating ; Feeding Behavior ; Female ; Hand ; Humans ; Reward ; Risk Factors