Phosphorylation of PSD-95 at serine 73 in dCA1 is required for extinction of contextual fear.

The updating of contextual memories is essential for survival in a changing environment. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular mechanisms of contextual fear memory updating remain poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic manipulations in vivo, combined with ex vivo 3D electron microscopy and electrophysiology, we identify a novel, synaptic mechanism that is induced during attenuation of contextual fear memories and involves phosphorylation of PSD-95 at Serine 73 in dCA1. Our data provide the proof that PSD-95-dependent synaptic plasticity in dCA1 is required for updating of contextual fear memory.

Mindful-Gratitude Practice Reduces Prejudice at High Levels of Collective Narcissism.

This research tested the hypothesis that mindful-gratitude practice attenuates the robust association between collective narcissism and prejudice. In Study 1 (a between-subjects study using a nationally representative sample of 569 Polish adults; 313 female), 10 min of mindful-gratitude practice-compared to mindful-attention practice and control-did not decrease prejudice (anti-Semitism), but weakened the positive link between collective narcissism and prejudice. In Study 2 (a preregistered, randomized, controlled-trial study using a convenience sample of 219 Polish adults; 168 female), a 6-week mobile app supported training in daily mindful-gratitude practice decreased prejudice (anti-Semitism, sexism, homophobia, anti-immigrant sentiment) and its link with collective narcissism compared to a wait-list control. The hypothesis-consistent results emphasize the social relevance of mindful-gratitude practice, a time- and cost-effective intervention.

Arc controls alcohol cue relapse by a central amygdala mechanism.

Alcohol use disorder (AUD) is a chronic and fatal disease. The main impediment of the AUD therapy is a high probability of relapse to alcohol abuse even after prolonged abstinence. The molecular mechanisms of cue-induced relapse are not well established, despite the fact that they may offer new targets for the treatment of AUD. Using a comprehensive animal model of AUD, virally-mediated and amygdala-targeted genetic manipulations by CRISPR/Cas9 technology and ex vivo electrophysiology, we identify a mechanism that selectively controls cue-induced alcohol relapse and AUD symptom severity. This mechanism is based on activity-regulated cytoskeleton-associated protein (Arc)/ARG3.1-dependent plasticity of the amygdala synapses. In humans, we identified single nucleotide polymorphisms in the ARC gene and their methylation predicting not only amygdala size, but also frequency of alcohol use, even at the onset of regular consumption. Targeting Arc during alcohol cue exposure may thus be a selective new mechanism for relapse prevention.

The shape of the change: Cumulative and incremental changes in daily mood during mobile-app-supported mindfulness training.

Understanding of the exact trajectories of mood improvements during mindfulness practice helps to optimize mindfulness-based interventions. The Mindfulness-to-Meaning model expects mood improvements to be linear, incremental, and cumulative. Our findings align with this expectation. We used multilevel growth curve models to analyze daily changes in positive mood reported by 190 Polish participants during 42 days of a mobile-app-supported, mindfulness-based intervention. The daily positive mood increased among 83.68% of participants. Participants who started the training reported worse mood improved more and faster than participants with better mood at the baseline. Dispositional mindfulness and narcissism - individual difference variables associated with high vs. low emotion regulation ability, respectively - were not associated with mood improvement trajectories. A small group of participants (16.32%) showed a steady decline in positive mood during the intervention. The results underscore the importance of a more comprehensive understanding of individual variability in benefiting from mindfulness-based interventions.

Impaired synaptic transmission in dorsal dentate gyrus increases impulsive alcohol seeking.

Both human and animal studies indicate that the dentate gyrus (DG) of the hippocampus is highly exploited by drug and alcohol abuse. Yet, it is poorly understood how DG dysfunction affects addiction-related behaviors. Here, we used an animal model of alcohol use disorder (AUD) in automated IntelliCages and performed local genetic manipulation to investigate how synaptic transmission in the dorsal DG (dDG) affects alcohol-related behaviors. We show that a cue light induces potentiation-like plasticity of dDG synapses in alcohol-naive mice. This process is impaired in mice trained to drink alcohol. Acamprosate (ACA), a drug that reduces alcohol relapse, rescues the impairment of dDG synaptic transmission in alcohol mice. A molecular manipulation that reduces dDG synaptic AMPAR and NMDAR levels increases impulsive alcohol seeking during cue relapse (CR) in alcohol mice but does not affect alcohol reward, motivation or craving. These findings suggest that hindered dDG synaptic transmission specifically underlies impulsive alcohol seeking induced by alcohol cues, a core symptom of AUD.

Generation of silent synapses in dentate gyrus correlates with development of alcohol addiction.

The brain circuits and synaptic processes that underlie alcohol addiction are currently the subject of intensive research. Here we focus on hippocampal circuitry and show that chemogenetic inhibition of dentate gyrus (DG) during presentation of alcohol-associated cues has long-lasting effects on mice behavior. DG inhibition enhances alcohol seeking and drinking, suggesting that DG regulates addiction-related behaviors. To test this hypothesis, we perform whole-cell patch-clamp recordings from the granule cells of DG and look for electrophysiological correlates of alcohol addiction. We observe that presentation of alcohol-associated cue light that induces relapse to alcohol-seeking results in generation of silent synapses, that lack functional AMPA receptors. Furthermore, using human criteria of addiction, we differentiate mice controlling their alcohol consumption from those that undergo transition to addiction to discover that the levels of silent synapses induced by alcohol cues are specifically increased in the addicted mice. As the total level of dendritic spines that harbor synapses is constant at this time point, our data indicate that synapses of perforant path to DG are weakened during cue relapse. Finally we demonstrate that, acamprosate, a drug that limits alcohol drinking and seeking in addicts, prevents generation of silent synapses in DG upon presentation of alcohol-associated cues. Altogether, our data suggest that weakening of DG synapses upon cue relapse contributes to persistent alcohol addiction-related behaviors.