Social memory, the ability to recall and comprehend social interactions, depends on hippocampal circuits, particularly the dorsal CA2. Disruptions in inhibitory transmission within CA2 have been implicated in neuropsychiatric and neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. However, the extrahippocampal mechanisms regulating CA2-dependent social memory remain poorly understood. The medial septum (MS), a major source of hippocampal afferents involved in network synchronization and information processing, has emerged as a potential modulator of social memory. Nevertheless, the contribution of MS GABAergic neurons to social memory remains unclear. Here, we selectively depleted MS GABAergic neurons using an anti-vesicular GABA transporter-saporin immunotoxin (anti-vGAT-SAP) and examined the resulting behavioral consequences. We found that loss of MS GABAergic neurons selectively impaired social memory, whereas sociability, social novelty preference and novel object recognition remain intact. In addition, lesioned animals exhibited impaired spatial memory together with increased locomotion, exploratory activity, and possible anxiolytic-like effects. These findings identify MS GABAergic neurons as a critical component of the neural circuitry underlying social memory and suggest that dysfunction of septal inhibitory signaling may contribute to the social and cognitive deficits associated with neuropsychiatric and neurological conditions.

Early-life adversity increases vulnerability to affective disorders, but the neural alterations underlying sex-dependent susceptibility remain unclear. Here, C57BL/6J mouse pups underwent maternal separation (MS) for 3 h daily from postnatal day 1 to 10, and adult male and female offspring were assessed behaviorally. MS induced significant anxiety-like behavioral alterations in male offspring, whereas comparable anxiogenic changes were not detected in females. c-Fos-based regional screening identified the hippocampus as a candidate region. In males, the reduction in c-Fos-positive cells was further localized to the dorsal and ventral dentate gyrus (DG), whereas females showed no significant change in overall hippocampal c-Fos expression. Transcriptomic analysis of the hippocampus revealed enrichment of inflammation-related pathways and downregulation of neurogenesis-related signatures, whereas histological analyses demonstrated reduced adult DG neurogenesis, including decreased quiescent and activated neural stem cells and reduced DCX immunoreactivity. These neurogenic alterations were accompanied by microglial activation, increased hippocampal pro-inflammatory cytokine expression, reduced IL-10 expression, and increased microglia-neural stem cell proximity. Together, these findings indicate that early-life maternal separation is associated with anxiety-like behavioral alterations in male offspring accompanied by reduced DG neurogenesis and hippocampal inflammatory alterations.

In contrast to the well-documented phenomena of inter-male aggression and competition in nature, the long-term consequences for females involuntarily exposed to persistent male-initiated social threat remain inadequately understood. In the present study, we demonstrate that C57BL/6J female mice co-housed with CD1 male mice for 14 days developed anxiety-like behaviors and cognitive deficits, without exhibiting depressive-like phenotypes. Concurrently, these females displayed a significant decrease in serum estrogen levels and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, co-housing with CD1 males profoundly disrupted sleep architecture in C57BL/6J females, as evidenced by reduced wakefulness and prolonged durations of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Mechanistically, these behavioral and physiological alterations were associated with substantial a reduction in cell density in the CA1 and CA3 subregions of the ventral hippocampus, accompanied by a marked downregulation of brain-derived neurotrophic factor (BDNF) within these same areas. Collectively, our findings provide experimental evidence for the adverse effects of chronic exposure to persistent male-initiated social threat on female recipients in a mammalian model, thereby offering a theoretical framework for understanding the enduring psychological trauma that may arise from sustained environments of psychological harassment, domestic violence, or sexual coercion-circumstances frequently encountered by women in human society.

Chronic alcohol exposure is a major driver of alcohol use disorders (AUD), in part through its ability to induce maladaptive plasticity within neural circuits that regulate reward, motivation, and affect. Excitatory projections from the hippocampus (Hipp) to the nucleus accumbens (NAc) play a pivotal role in regulating reward-related behaviors, and this pathway serves as a key locus for establishing associations between rewarding stimuli and related contextual information. Regulation of the strength of Hipp-NAc synapses is critical for supporting these behaviors, and impairments in Hipp-NAc plasticity are associated with anhedonia and disrupted reward learning. Here, we demonstrate that acute ethanol application to ex vivo brain slices prevents long-term potentiation (LTP) at Hipp-NAc synapses without altering presynaptic release probability. Furthermore, chronic intermittent exposure to ethanol abolishes LTP at these synapses, an effect we observed during early abstinence indicating that ethanol-induced disruptions in Hipp-NAc plasticity outlasts exposure periods. Together, our findings demonstrate that ethanol rapidly alters Hipp-NAc plasticity, and its effects are still evident in early abstinence. Given the behavioral relevance of these synapses, this work has important implications for the mechanisms underlying ethanol-dependent effects on reward processing and negative affective states associated with AUD.

Facial expressions are important cues for conveying social-emotional information, and their processing unfolds across multiple neural stages. The study employed event-related potentials to examine the neural dynamics of facial-expression change detection while testing the role of sports expertise. It further examined whether N170 responses showed prediction-error-related enhancement. Non-athletes, team-sport athletes, and individual-sport athletes completed ignore- and attend-oddball tasks, with angry and happy faces presented as rare stimulus types (deviants) and neutral faces as the frequent stimulus type (standard). An ignore-equiprobable task provided physically identical, probability-matched control stimuli for angry and happy deviants. For P1 in both oddball conditions, amplitudes were smaller for happy than for angry and neutral faces, suggesting expression-related modulation during early sensory encoding. For N170, amplitudes showed a robust graded pattern (angry > happy > neutral, more negative) in each task condition, indicating sensitivity to expression category during perceptual face representation. For P3b in the attend-oddball condition, amplitudes were larger for angry and happy faces than for neutral faces, and larger for angry than for happy faces, consistent with greater resource allocation to rare emotional targets, particularly angry faces, during task-relevant target detection and stimulus evaluation. Separately, comparison of N170 responses to probability-matched deviant and control stimuli provided no evidence for prediction-error-related N170 enhancement for either angry or happy faces. No reliable modulation by sports expertise was observed in the present sample and task conditions. Overall, multistage neural responses were strongly shaped by expression category, highlighting expression-related effects on early sensory, perceptual, and later evaluative processing.

It is a methodological challenge to induce robust alcohol self-administration in rats without the use of involuntary consumption methods or sweeteners. The present work compares the efficacy of liquid and gelatin media, with and without sucrose fading, in voluntary alcohol-self administration using a rat Drinking in the Dark paradigm. Sprague-Dawley rats were reared under group housed, enriched conditions. A subset of rats was moved to non-enriched single housing conditions prior to the start of experimentation to model the acute stress produced by isolation housing common to self-administration paradigms. Over the course of 21 days of alcohol self-administration, rats in the gelatin groups consumed more than those in the liquid groups, regardless of sucrose fading condition. Sucrose fading produced a transient increase in self-administration in the liquid group but produced no escalation in gelatin groups. Gelatin groups persist in drinking at higher concentrations of quinine than liquid groups. No effects of housing condition were observed. These findings suggest that robust ethanol self-administration behavior can be established in rats by employing a gelatin medium without the need for acquisition aids such as sucrose.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which alterations in the microbiota-gut-brain axis has been increasingly investigated. However, the effects of individual cultivable bacterial isolates recovered from individuals with AD on host intestinal and neurobehavioral phenotypes remain insufficiently characterized. In this study, three bacterial isolates, Escherichia coli, Klebsiella pneumoniae, and Citrobacter pasteurii, were recovered from fecal samples collected from individuals diagnosed with AD and evaluated in healthy BALB/c mice following long-term oral administration. The effects of the isolates on physiological parameters, intestinal morphology and barrier-associated markers, inflammatory responses, gut microbial community composition, and neurobehavioral outcomes were assessed. The three isolates produced strain-specific effects, with C. pasteurii producing the most pronounced overall phenotype. Mice receiving C. pasteurii showed reduced body weight gain, increased spleen index, and shortened colon length, accompanied by elevated circulating inflammatory cytokines. Alterations in goblet cells, MUC2 expression, and tight-junction-associated proteins, including ZO-1 and claudin-1, were also observed, indicating alterations in intestinal barrier-associated structures. Gut microbiota analysis revealed strain-specific changes in microbial diversity and community composition, with the most pronounced alterations observed in the C. pasteurii group. In addition, C. pasteurii administration was associated with increased hippocampal inflammatory responses and astrocytic activation, whereas no apparent hippocampal neuronal loss was detected. Neurobehavioral testing revealed reduced locomotor activity and altered exploratory and behavioral responses, particularly in the C. pasteurii group. However, because reduced locomotor activity may influence performance in the novel object recognition and tail suspension tests, these findings should be interpreted cautiously. K. pneumoniae produced intermediate effects, whereas E. coli showed comparatively limited effects under the experimental conditions used. Collectively, these findings indicate that the tested bacterial isolates recovered from individuals with AD can produce strain-specific intestinal, inflammatory, microbial, and neurobehavioral alterations in healthy mice, with C. pasteurii producing the strongest overall phenotype. Importantly, the observed changes in gut microbial composition do not establish specific bacterial functions or pathogenicity, as microbial functional activity was not directly assessed. The present study does not establish that these bacteria are specifically associated with AD or that they cause AD progression; rather, it provides experimental evidence that individual cultivable bacterial isolates recovered from individuals with AD may differentially influence host phenotypes relevant to processes implicated in neurodegenerative disease. Further studies using larger human cohorts with appropriate healthy controls, validated AD models, and direct functional and mechanistic investigations are required to clarify the relevance of these observations to AD pathophysiology.

Paraquat (PQ) exposure induces oxidative stress, behavioral impairment, and monoaminergic dysfunction in experimental models. This study evaluated the effects of a complete açaí (Euterpe oleracea) oil-loaded nanocapsule formulation (AON) on alterations associated with short-term PQ exposure in Drosophila melanogaster. A preliminary 5-day screening evaluated AON suspension concentrations from 0.2 % to 2.0 % (v/v), after which 0.2 % and 2.0 % were selected for a 5-day co-exposure experiment with 1.8 mM PQ. Each treatment was evaluated in five independent experimental runs, with one vial containing 50 flies constituting one biological replicate. PQ reduced survival, impaired climbing, and reduced open-field activity; it also increased reactive oxygen species and lipid peroxidation, altered catalase and superoxide dismutase activities, and affected acetylcholinesterase activity, dopamine, and serotonin. Co-treatment with the AON formulation was associated with higher survival and attenuation of climbing, oxidative, and selected neurochemical alterations relative to PQ alone. In the variance-robust analysis of open-field activity, the 0.2 % AON co-treatment differed from PQ alone, whereas the 2.0 % co-treatment did not. AON at 2.0 % alone also reduced open-field activity relative to the control. Under the present 5-day conditions, the complete AON formulation attenuated several PQ-associated endpoints; however, the study did not include non-encapsulated açaí oil or empty nanocapsules and therefore does not establish an advantage of nanoencapsulation or the contribution of individual formulation components.

Syllable perception requires the continuous integration of segmental (consonants and vowels) and suprasegmental (lexical tones) information. While native listeners of tonal languages exhibit pre-attentive integration of these dimensions, it remains unclear whether non-tonal second language (L2) learners can develop such integration through L2 experience. The present study employed electroencephalogram (EEG) to record mismatch negativity (MMN) responses in a passive oddball paradigm, investigating the perceptual integration of consonants, vowels, and tones. Twenty-four native Mandarin listeners (L1 group) and fifteen non-tonal L2 learners of Mandarin (L2 group) were recruited. Stimuli included a standard syllable (/da1/), three single-deviants (/ga1/, /du1/, /da4/), and three double-deviants (/gu1/, /ga4/, /du4/). MMN additivity analyses compared original double-deviant MMN amplitudes against the sum of corresponding single-deviant MMN amplitudes. The L1 group exhibited robust sub-additive MMN patterns across all double-deviant combinations (consonant-vowel [CV], consonant-tone [CT], and vowel-tone [VT]), demonstrating integrated processing across all phonological dimensions. The L2 group showed delayed MMN peak latencies and reduced pre-attentive sensitivity to single consonant and single tone deviations. Crucially, they exhibited additivity for CV and CT combinations (independent processing), but a selective sub-additive trend for the VT combination, which we interpret as preliminary evidence for vowel-tone integration. These findings provide tentative support for the TTRACE model and refine the dimensional transfer hypothesis, suggesting that non-tonal L1 biases may be partially overcome through L2 experience when phonological dimensions share tight acoustic proximity within the syllable nucleus (i.e., vowel-tone integration). Non-tonal L2 learners display a developmental pattern rooted in acoustic salience and bottom-up physical binding.

Respiratory failure is a leading cause of mortality in coronavirus disease 2019 (COVID-19). While the brainstem centrally governs respiratory control, its ascending arousal nuclei regulate consciousness and wakefulness. Many COVID-19 patients exhibit prolonged unresponsiveness or delayed arousal from sedation. These clinical observations suggest the potential involvement of the brainstem and its associated arousal systems. However, region-specific structural and microstructural differences in the brainstem and ascending arousal network following COVID-19 remains unclear. We analyzed previously collected structural and diffusion-weighted magnetic resonance imaging data from 73 COVID-19 patients (mean age: 42.1 years) and 27 age-matched non-COVID-19 controls (mean age: 42.8 years). Diffusion data were available for 71 and 18 COVID-19 and non-COVID-19 participants, respectively. Regional volumes were normalized to estimated total intracranial volume, and diffusion tensor measures included fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. In false-discovery-rate-adjusted analyses, the COVID-19 group had a larger normalized superior cerebellar peduncle (SCP) volume and smaller ventral tegmental area and periaqueductal gray volume. In the diffusion subset, the SCP showed lower fractional anisotropy and axial diffusivity and higher radial and mean diffusivity, indicating subtle but nonspecific differences in tissue microstructural organization. Within the COVID-19 group, higher anxiety scores were associated with lower midbrain volume. These findings identify region-specific structural and microstructural differences involving the SCP and selected arousal-related nuclei in individuals assessed during the post-acute phase of COVID-19. The inverse association between anxiety and midbrain volume suggests potential clinical relevance. However, higher-resolution, prospectively acquired multimodal studies are needed to determine whether these observations are related to post-COVID respiratory, arousal, or neuropsychiatric symptoms.