Pablo R. Moya

Stressing rodent dams during lactation can impair offspring neurodevelopment, altering behavioral and physiological outcomes. Witnessed social defeat stress (WSDS) is a paradigm in which a juvenile or adult rodent observes aggressive encounters, affecting stress physiology and behavior. We developed a novel early‐life stress model by exposing lactating rat dams to WSDS and assessed its impact on juvenile social behavior and stress‐related physiology. At postnatal day 24, same‐sex, age‐matched pairs of offspring were tested for social play by scoring pouncing (play initiation), pinning, chasing, and evading. Locomotor activity was assessed in the open field on the same day. After behavioral testing, adrenal cortex weight was measured as an indirect marker of stress‐related physiology. Maternal WSDS exposure was associated with a significant sex × WSDS interaction in pouncing behavior, with reduced pouncing in juvenile males, whereas no comparable effect was observed in females. WSDS exposure also increased adrenal cortex weight overall, although the sex × WSDS interaction for this measure was not significant. The reduction in pouncing was characterized by substantial within‐group variability, and randomization‐based sensitivity analysis indicated that the statistical significance of the sex × WSDS interaction was sensitive to focal‐animal assignment. These findings suggest that maternal WSDS exposure may produce a specific and variable alteration in social play initiation, together with changes in stress‐related physiology, during early juvenile development. This model may provide a useful framework for investigating how maternal psychosocial stress influences offspring behavioral and physiological development.

Executive functions are a set of cognitive processes that regulate behavior and adapt responses to changing demands. Impairments in these processes are common in various neuropsychiatric conditions, including obsessive-compulsive disorder. Mice overexpressing the neuronal glutamate transporter EAAT3 in the forebrain (EAAT3glo/CaMKII) exhibit increased compulsive behaviors and synaptic alterations relevant to OCD. However, whether EAAT3 overexpression affects executive functioning across multiple cognitive domains has not been studied. Using operant conditioning and visuospatial learning tasks, we evaluated the performance of EAAT3glo/CaMKII mice across three behavioral domains commonly associated with executive function: cognitive flexibility, working memory, and inhibitory control. EAAT3glo/CaMKII mice showed impaired cognitive flexibility in both operant extinction and reversal learning. EAAT3glo/CaMKII mice also failed to acquire the Trial-unique, delayed nonmatching-to-location task, suggesting impaired working memory, and showed increased impulsivity in the five-choice serial reaction time task, as evidenced by elevated premature responses. Perseverative responses, response accuracy, and attentional performance were unaffected in EAAT3glo/CaMKII mice. Collectively, these findings suggest that EAAT3 overexpression in forebrain neurons is associated with a cognitive profile characterized by difficulties in flexibility and task acquisition, alongside increased impulsivity, while attentional performance and motivational measures remain intact in a model of compulsive behavior.

Long-term depression (LTD) is a form of synaptic plasticity implicated in tasks involving the modification or elimination of previously learned information. While glial glutamate transporters can control the strength of synaptic plasticity, much less is known about the contribution of the neuronal glutamate transporter EAAT3 in controlling hippocampal LTD and learning processes. Here, we report that overexpression of EAAT3 in principal neurons, but not in GABAergic interneurons, impairs heterosynaptic GABAergic synaptic plasticity (iLTD) and homosynaptic excitatory LTD in the hippocampus. LTD impairments can be reversed by inhibiting EAAT3 or by a brief exogenous activation of mGluR during LTD induction, suggesting that, by limiting glutamate spillover between neighboring synapses, EAAT3 contributes to setting the strength of different forms of hippocampal LTD. Moreover, mice overexpressing EAAT3 in principal neurons, but not in GABAergic interneurons, display impaired reversal learning, a phenotype that can be rescued by blocking EAAT3 in vivo . Together, these findings reveal that, by controlling the strength of hippocampal LTD, EAAT3 contributes to cognitive flexibility required for processing new information. Significance statement: Cognitive flexibility, particularly reversal learning, depends critically on the ability to weaken outdated synaptic connections, a cellular process mediated by long-term depression (LTD), that enables new memories to be stored in overlapping circuits. While astrocytic glutamate transporters are known to shape synaptic plasticity, the contribution of neuronal glutamate transporter EAAT3 has remained unclear. Here we identify EAAT3 as a key factor for hippocampal LTD and behavioral flexibility. Overexpression of EAAT3 in principal neurons, but not in GABAergic interneurons, impairs homosynaptic and heterosynaptic forms of LTD, and produces perseverative deficits in hippocampal-mediated reversal learning tasks that are rescued by EAAT3 blockade. These findings reveal that neuronal glutamate uptake, likely by limiting glutamate spillover between neighboring synapses, plays an important role in setting the threshold for multiple forms of hippocampal LTD and establishing a mechanistic link between EAAT3, synaptic depotentiation, and the capacity to update learned information in vivo .

Serotonin (5-HT) plays an important role in shaping brain network dynamics by regulating excitatory synaptic function and neuronal excitability. However, much less is known about how 5-HT tunes synaptic inhibition. Here, we demonstrate that transient 5-HT signaling persistently suppresses GABAergic synapses onto layer 2/3 pyramidal neurons in the medial prefrontal cortex (mPFC). Moreover, we found that 5-HT1A and 5-HT2A receptors differentially contribute to 5-HT regulation of synaptic inhibition, possibly by acting at distinct GABAergic cell subpopulations. Importantly, 5-HT2A receptor activation triggers retrograde endocannabinoid signaling to reduce GABA release selectively at synapses formed by somatostatin (SST+)- but not parvalbumin (PV+)-positive GABAergic interneurons. Altogether, our results highlight the diverse molecular and cell-type-specific mechanisms by which 5-HT signaling modulates inhibitory circuits to shape cortical function.

Automatic radiology report generation (ARRG) has emerged as a promising application of deep learning (DL) with the potential to alleviate reporting workload and improve diagnostic consistency. However, despite rapid methodological advances, the field remains technically fragmented and not yet mature for routine clinical adoption. This scoping review maps the current ARRG research landscape by examining DL architectures, multimodal integration strategies, and evaluation practices from 2015 to April 2025. Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, a comprehensive literature search identified 89 eligible studies, revealing a marked predominance of chest radiography datasets (87.6%), primarily driven by their public availability and the accelerated development of automated tools during the COVID-19 pandemic. Most models employed hybrid architectures (73%), particularly CNN–Transformer pairings, reflecting a shift toward systems that combine local feature extraction with global contextual reasoning. Although these approaches have achieved measurable gains in textual and semantic coherence, several challenges persist, including limited anatomical diversity, weak alignment with radiological rationale, and evaluation metrics that insufficiently reflect diagnostic adequacy or clinical impact. Overall, the findings indicate a rapidly evolving but clinically immature field, underscoring the need for validation frameworks that more closely reflect radiological practice and support future deployment in real-world settings.

Automatic radiology report generation (ARRG) has emerged as a promising application of deep learning (DL) with the potential to alleviate reporting workload and improve diagnostic consistency. However, despite rapid methodological advances, the field re-mains technically fragmented and not yet mature for routine clinical adoption. This systematic review maps the current ARRG research landscape by examining DL archi-tectures, multimodal integration strategies, and evaluation practices from 2015 to April 2025. A PRISMA-compliant search identified 89 eligible studies, revealing a marked predominance of chest radiography datasets (87.6%), largely driven by their public availability and the accelerated development of automated tools during the COVID-19 pandemic. Most models employed hybrid architectures (73%), particularly CNN–Transformer pairings, reflecting a shift toward systems capable of combining local feature extraction with global contextual reasoning. Although these approaches have achieved measurable gains in textual and semantic coherence, several challenges per-sist, including limited anatomical diversity, weak alignment with radiological reason-ing, and evaluation metrics that insufficiently reflect diagnostic adequacy or clinical impact. Overall, the findings indicate a rapidly evolving but clinically immature field, underscoring the need for validation frameworks that more closely reflect radiological practice and support future deployment in real-world settings.

Bipolar disorder (BD) may present with neurocognitive dysfunction due to inflammatory alterations through different biological pathways. However, findings are not consistent regarding the patterns of neurocognitive dysfunction and elevation of inflammatory biomarkers during the different mood phases. Therefore, we aimed to determine associations between inflammatory biomarkers, neurocognitive functioning, and clinical outcomes in patients with BD in euthymia. We conducted a cross-sectional study including 109 adults. Serum levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), neurocognitive parameters (ACER), number of suicide attempts (SA), and hospitalizations (NH) were measured. We found negative and moderate correlations between IL-6 and ACER total score, language, visuospatial abilities, and orientation/attention. There was a positive and moderate correlation between IL-6 and NH. IL-6 significantly predicted ACER total score, language, memory, orientation/attention, visuospatial abilities, and NH. Overall, IL-6 had an inverse association with neurocognition and clinical variables, whereas hs-CRP did not play a role. Here we demonstrate that IL-6 predicts neurocognitive functioning in adults with BD. BD may be a biological model for studying the relationship between inflammation and neurocognition in severe psychiatric disorders. Prospective studies at different mood phases of the disease must be conducted.

FKBP5 has been of special scientific interest in the behavioral sciences since it has been involved in the pathophysiology of several mental disorders. It is a gene with pleiotropic effects which encodes the protein FKBP5, a cochaperone that decreases glucocorticoid receptor (GR) affinity for glucocorticoids by competing with FKBP4, altering the GR chaperone complex, and impairing GR activation. As a key modulator of the stress response, FKBP5 plays a critical role in regulating cortisol levels in the organism. The FKBP5 gene is regulated through a combination of transcriptional, epigenetic, post-transcriptional, and environmental mechanisms, as well as genetic polymorphisms that influence its transcription and stress responsiveness. Notably, the rs1360780 T-allele in FKBP5 significantly affects FKBP5 regulation and has been linked to stress-related disorders by influencing transcription and stress responsiveness. In this narrative review, we aim to provide an overview of the role played by the single-nucleotide polymorphism rs1360780 in the FKBP5 locus in gene expression, its epigenetic regulation, and the impact of early stress in its functioning. We discuss some brain regions with differential expression of FKBP5 and some behavioral phenotypes linked to the locus. The T-allele of rs1360780 is considered a risk variant, as it leads to high FKBP5 induction, which delays negative feedback and increases GR resistance. This results in states of relative hypercortisolemia and brain morphofunctional alterations, particularly in regions sensitive to glucocorticoid activity during critical periods of neurodevelopment. Additionally, exposure to childhood maltreatment is associated with demethylation of the glucocorticoid response elements of FKBP5, further increasing its expression levels. Among the psychological dimensions analyzed in which FKBP5 is involved are neurocognition, aggression, suicidality, and social cognition. At the level of mental disorders, the gene may play a role in the pathogenesis of post-traumatic stress disorder, depression, and bipolar disorder. In psychotic disorders, its role is less clear. This knowledge enhances the understanding of disease mechanisms that operate through psychopathological dimensions, and highlights the need to design specific, person-centered psychopharmacological and environmental therapeutic interventions.

Depression is a disabling and highly prevalent psychiatric illness. Multiple studies have linked glutamatergic dysfunction with the pathophysiology of depression, but the exact alterations in the glutamatergic system that contribute to depressive‐like behaviors are not fully understood. Recent evidence suggests that a decreased level in neuronal glutamate transporter (EAAT3), known to control glutamate levels and limit the activation of glutamate receptors at synaptic sites, may contribute to the manifestation of a depressive phenotype. Here, we tested the possibility that increased EAAT3 expression at excitatory synapses could reduce the susceptibility of mice to develop depressive‐like behaviors when challenged to a 5‐week unpredictable chronic mild stress (UCMS) protocol. Mice overexpressing EAAT3 in the forebrain (EAAT3^glo/CMKII) and control littermates (EAAT3^glo) were assessed for depressive‐like behaviors and long‐term memory performance after being subjected to UCMS conditions. We found that, after UCMS, EAAT3^glo/CMKII mice did not exhibit depressive‐like behaviors or memory alterations observed in control mice. Moreover, we found that EAAT3^glo/CMKII mice did not show alterations in phasic dopamine release in the nucleus accumbens neither in long‐term synaptic plasticity in the CA1 region of the hippocampus after UCMS, as observed in control littermates. Altogether these results suggest that forebrain EAAT3 overexpression may be related to a resilient phenotype, both at behavioral and functional level, to the deleterious effect of chronic stress, highlighting the importance of neuronal EAAT3 in the pathophysiology of depressive‐like behaviors. image