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Barroso-Flores, J.

Publications and source records attributed to Barroso-Flores, J..

3 recordsLinked to original sources

A Dual-Ensemble Model of Infralimbic Cortex Function in Behavioural Flexibility

The infralimbic cortex (IL) has been described as both facilitator and terminator of reward-seeking, yet both functions appear mutually exclusive. We reconcile this discrepancy by proposing a dual-ensemble model: one for action-outcome prediction and another for prediction correction. Using longitudinal miniscope imaging in rats, we show that during training, the action-outcome predictor ensemble sharpens its activity by suppressing the majority of the IL neuronal population. As contingencies stabilize, entropy decreases, reflecting a refined predictive model. During extinction, the prediction correction ensemble activates in response to reward omission. A computational simulation based on these two ensembles successfully recapitulated our experimental results. This framework reconciles conflicting models, where IL manipulation can either accelerate or abolish extinction by demonstrating that IL activity dynamically encodes predictive accuracy. Our findings indicate that IL functions as an action-outcome predictor that elegantly guides behavioural flexibility.

neuroscience↗

A common molecular mechanism for cognitive deficits and craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

neuroscience↗

Piperazine-based HIV-1 entry inhibitors: Massive in silico library design and screening for gp120 attachment inhibitors.

HIV-1 attachment, despite being an ideal target stage to stop infection from the beginning, remains as one of the HIV lifecycle phases with less amount of designed and commercially available inhibitors. To contribute to the urgently needed discovery of new active compounds that could become part of the current highly active antiretroviral therapy, and as an attempt to explore a massive chemical space, high-throughput virtual screening of 16.3 million combinatorially generated and piperazine-cored compounds, was accomplished. Docking calculations, molecular dynamics simulations, and QSAR analyses were carried out to assess the suitability of each ligand to bind gp120 envelope glycoprotein, thus preventing it from binding to CD4 co-receptor. Ligand 255 stands out as a promising candidate to be tested beyond computational methodologies, and the 4,5,6,7-tetrahydroindole fragment is reported as a better group to bind inside the Phe43 cavity than the substituted indoles reported in the literature.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC=\"FIGDIR/small/330142_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (26K):\norg.highwire.dtl.DTLVardef@fe054dorg.highwire.dtl.DTLVardef@10e3501org.highwire.dtl.DTLVardef@1b9de6dorg.highwire.dtl.DTLVardef@1b9cb18_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗