Frontiers in Behavioral Neuroscience最新文献

Adolescence is a period of transition from childhood to adulthood in which subjects exhibit characteristic behaviors, such as increases in impulsivity, social interactions, novelty-seeking and risk-taking behaviors. Previous studies have shown that adolescents often respond prematurely in operant tasks, but it remains unclear whether this behavior reflects general hyperactivity, cognitive impairments, or if it is a specific form of impulsivity. Here, we trained male and female adolescent and adult Long-Evans rats in a rewarded operant task that required withholding an action sequence for a 2.5 s waiting time. Adolescent males exhibited significantly more premature responses than females or adults, despite achieving similar reward rates. To test whether this behavior was associated with other traits, we assessed locomotor activity in the Open Field and recognition memory in the Y-maze. Locomotor activity and memory performance were comparable between groups, indicating that the increased premature responding observed in adolescent males was not readily explained by differences in general activity levels or cognitive performance. Together, these findings suggest that impulsive responding during adolescence shows a sex-dependent expression and reflects a distinct behavioral component within the context of this task, rather than belonging to broader behavioral differences. Understanding the specificity of adolescent impulsivity may provide insights into vulnerability to risk-taking and psychiatric disorders during adolescence.

Promotive behavior refers to actions that facilitate individuals' efforts to surmount obstacles and proactively pursue their goals, thereby fostering adaptive functioning and positive development. In contrast, prohibitive behavior refers to harmful or otherwise maladaptive actions that may hinder individuals' personal growth and developmental outcomes. This study aims to explore the possible causal relationship between Internet use behavior and adolescent behavioral development, including promotive behavior and prohibitive behavior. There were 9,132 students' data that were analyzed, and cross-lagged regression analysis was used to study causal relationships between two or more variables that change over time. Data were collected at two time points: T1 (2013-2014) and T2 (2014-2015), with an interval of approximately 1 year between the two waves. Results indicated a negative correlation between Internet use behavior and promotive behavior at points-in-time T1 and T2, while a positive relationship was observed between Internet use behavior and prohibitive behavior at both time points. Findings suggest that reducing problematic Internet use among adolescents contributes to the development of healthy behaviors, and active and healthy adolescent behaviors can in turn reduce their problematic Internet use.

Objective: This study aimed to examine the impact of the teacher-student relationship on moral consensus among primary school students, and to investigate the roles of mindfulness, grateful disposition, and social and emotional skills in this relationship.

Methods: Using a cluster sampling method, 2,800 students from grades 3 to 5 across three schools in Guizhou Province completed collective questionnaires offline. Data were analyzed using SPSS 27.0 and the SPSS macro PROCESS to test the hypothesized model. The significance of all regression coefficients was tested using the Bootstrap method.

Results: The teacher-student relationship significantly and positively predicted moral consensus (c = 0.48, SE = 0.02, p < 0.001). Social and emotional skills and grateful disposition partially mediated the relationship between the teacher-student relationship and moral consensus (a₁b₁ = 0.12, Boot SE = 0.01; a₂b₂ = 0.08, Boot SE = 0.01). Mindfulness significantly moderated the first part of the mediation pathway involving the teacher-student relationship and social and emotional skills. As the level of mindfulness increased, the positive predictive effect of the teacher-student relationship on social and emotional skills strengthened (B _simple at high mindfulness = 0.50, t = 23.74, p < 0.001, increasing from B _simple = 0.41 at low mindfulness). However, the moderating effect of mindfulness was not significant when grateful disposition served as the mediator.

Conclusions: These findings enhance the understanding of the mechanisms through which the teacher-student relationship influences moral consensus and provide practical implications for fostering moral consensus among primary school students.

Adolescent binge drinking in humans is associated with adverse outcomes, here we examined sex- and withdrawal-dependent changes in affective behaviors and metabolomic profiles in male and female mice following AIE exposure. Male and female C57BL/6 J mice were exposed to intermittent ethanol vapor inhalation from postnatal (PND) 28-42, a model of intermittent binge-like ethanol exposure during adolescence. Affective behavior was assessed using the open field test (OFT), light/dark test (LDT), and tail suspension test (TST) during short-term withdrawal (PND 49-53) and again during long-term withdrawal (PND 91-95). Serum samples were collected 24 h after the final exposure cycle (PND 43), fecal samples were collected during each OFT, and liver samples were collected at euthanasia (PND 119; ~80 days after exposure) for metabolomic analysis. Ethanol sensitivity in adulthood was additionally assessed using loss of righting reflex (LORR) on PND 116. Overall, AIE produced modest, sex- and withdrawal-dependent behavioral effects, whereas metabolomic differences were most pronounced in males shortly after exposure and diminished with longer withdrawal. These findings support future work testing whether early metabolomic shifts track later behavioral vulnerability.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory deficits. Mounting evidence highlights the role of cholinergic and histaminergic neurotransmissions in the pathophysiology of AD. Hence, developing agents that target multiple neurotransmitter systems may provide improved therapeutic benefits.

Methods: This study investigated the effects of acute systemic administration of E100, a dual-active cholinesterase inhibitor (ChEI) and histamine H3 receptor (H3R) antagonist, on scopolamine (SCO)-induced memory impairment in male C57BL/6 mice. Behavioral assessments, including the Novel Object Recognition Test (NORT), Y-Maze test (YMT), Three-Chamber Test (TCT), Fear Conditioning test (FCT), and Elevated Plus Maze (EPM), were conducted to assess cognitive performance while biochemical analyses assessed apoptotic markers, oxidative stress, neuroinflammation and acetylcholinesterase activity.

Results: Systemic administration of E100 (10 mg/kg, i.p.) significantly improved memory function in SCO-induced amnesia, as evidenced by enhanced short-term memory (STM) (p < 0.001) and long-term memory (LTM) (p < 0.01) performance in the NORT, as well as improved spatial memory in YMT (p < 0.001) and FCT (p < 0.001; for cued fear memory) and (p < 0.001; for contextual fear memory). Additionally, E100 treatment in the TCT, improved social memory (p < 0.001) and alleviated SCO-induced anxiety-related deficits in the EPM (p < 0.001). Moreover, treatment with E100 (10 mg/kg, i.p.) attenuated SCO-induced neuroinflammation by reducing TNF-α and IL-1β levels and mitigated oxidative stress by increasing GSH and SOD while decreasing MDA levels in the hippocampus and cerebellum (p's < 0.001). E100 also reduced caspase-1 activity (p < 0.001), suggesting its anti-apoptotic effect. Furthermore, E100 attenuated the elevated AChE activity observed in SCO-induced amnesic mice (p < 0.01), providing effects comparable to those of the reference drug Donepezil.

Discussion: These findings provide extensive in vivo evidence of the neuroprotective effects of E100, demonstrating its ability to ameliorate memory deficits, mitigate neuroinflammation and restore oxidative as well as AChE activity balance. By targeting both cholinergic and histaminergic dysfunction in the brain, E100 offers a promising therapeutic strategy for AD and related neurodegenerative disorders. This study highlights the potential role of dual-active ChEIs and H3R antagonists in memory impairment, and addressing multiple neuropathological mechanisms underlying AD.

The cerebellum is critically involved in both motor coordination and affective regulation, and growing evidence suggests that cerebellar dysfunction contributes to neuropsychiatric disorders. While much attention has focused on synaptic signaling and calcium homeostasis, the role of potassium channels in cerebellar function remains relatively understudied. Here, we investigated the role of the potassium channel ROMK (renal outer medulla K⁺ channel) in cerebellar signaling and behavior using cre/loxP gene knockout in Pcp2cre-expressing cells. Surprisingly, ROMK expression was detected in a distinct cell population within the cerebellar granule layer, rather than in Purkinje cells, yet this expression was effectively targeted by Pcp2cre-mediated recombination. Mutant mice showed normal Purkinje cell density and soma size, but increased dendrite diameter. At the molecular level, we observed downregulation of cerebellar subtype-specific genes and potassium channel subunits, along with changes in markers of translational signaling. Increased presence of GFAP-positive cells further suggested underlying neuronal stress in the ROMK-deficient cerebellum. Behaviorally, ROMK-deficient mice exhibited clear impairments in motor coordination and heightened anxiety-like behavior in the elevated plus maze (EPM). Our findings link ROMK loss to molecular and cellular remodeling in the cerebellum and support the idea that ROMK contributes to neural circuits that regulate complex behaviors, providing a framework for further studies in this direction.

The reproducibility crisis and translational gap in preclinical research underscore the need for more accurate and reliable methods of health monitoring in animal models. Manual testing is labor-intensive, low-throughput, prone to human bias, and often stressful for animals. Although many smart cages have been introduced, they have seen limited adoption due to either low throughput (being limited to single animals), low data density (a few metrics only), high costs, a need for new space or infrastructure in the vivarium, high complexity use, or a combination of the above. Although technologies for video-based single-animal tracking have matured, no existing technology enables robust and accurate multi-animal tracking in standard home cages. To solve these problems, we built a new type of assay device: the Smart Lid. Smart Lids mount to existing racks, above standard home cages and stream video and audio data, turning regular racks into high-throughput monitoring platforms. To solve the multi-animal tracking problem, we developed a new computer vision pipeline (MOT - Multi-Organism Tracker) along with a new ear tag purpose-designed for computer vision tracking. MOT achieves over 97% accuracy in multi-animal tracking while maintaining an affordable runtime cost (less than $100 per month). The pipeline returns 21 health-related metrics, covering activity, feeding, drinking, rearing, climbing, fighting, cage positioning, social interactions and sleeping, with additional metrics under development.

Cognitive decline is a major non-motor symptom in patients with Parkinson's disease (PD) that can be present as early as the prodromal stage. As a multisystem neurodegenerative syndrome, PD is associated with disturbances in various neurotransmitters, including dopamine, acetylcholine, serotonin, noradrenaline, glutamate, and gamma-aminobutyric acid (GABA). While the roles of dopaminergic and cholinergic deficiencies in cognitive impairment in PD are well documented, the contribution of the GABAergic system is less clear. We investigated spatial and recognition memory, along with changes in hippocampal GABAergic parvalbumin-positive (PV+) neurons, in distinct rat models of PD neuropathology. PD cholinopathy was induced by bilateral pedunculopontine tegmental nucleus (PPT) lesion, hemiparkinsonism was induced by unilateral substantia nigra pars compacta (SNpc) lesion, and hemiparkinsonism with PD cholinopathy was induced by unilateral SNpc and bilateral PPT lesions. Behavioral tests were conducted 14 and 42 days after lesions and included assessments of spatial memory (spatial habituation test), recognition memory (novel object recognition test), and measurements of motor activity (open field test). Motor function was preserved in all PD models. We observed delayed impairments in spatial and recognition memory in PD cholinopathy, and persistent impairment in spatial memory in hemiparkinsonism, although hippocampal PV expression remained unchanged over time. In hemiparkinsonism with PD cholinopathy, persistent spatial memory impairment was followed by delayed recognition memory deficits, along with hippocampal PV suppression, which was functionally linked to recognition memory impairment. Our results show that different PD neuropathologies underlie different memory impairments in rats. While dopaminergic denervation plays an important role in impairing spatial memory from the prodromal stage of PD, cholinergic denervation impairs recognition memory in a delayed manner. However, only their synergistic dysfunction alters hippocampal GABAergic PV+ neuron-mediated inhibitory transmission during PD progression, which was correlated with memory impairment.

Stress exposure can disrupt fear extinction, which is a hallmark of some stress-related disorders. The underlying molecular mechanisms of impaired extinction, especially in females, remain poorly understood. In this study, we investigated proteomics changes in the infralimbic cortex, a region critical for fear suppression, in female rats exposed to single prolonged stress (SPS). One week after SPS exposure, adult female rats underwent auditory fear conditioning and extinction training and were classified as susceptible or resilient based on their extinction performance. Quantitative proteomics using tandem mass tag labeling combined with bioinformatics analysis identified distinct proteins and pathways differentiating the groups. Susceptible rats displayed unique proteomic profiles in the infralimbic cortex. Several of the 53 differentially expressed proteins are associated with synaptic plasticity and memory, including neurogranin and microtubule-associated protein tau (MAPT). Pathway enrichment analysis identified alterations in synaptogenesis, clathrin-mediated endocytosis, calcium signaling, and chaperone-mediated autophagy. Functional validation using AAV-shRNA knockdown of neurogranin or MAPT in CAMKIIα-expressing neurons of the infralimbic cortex improved extinction memory in SPS-exposed animals. Our findings suggest that dysregulated protein expression in the infralimbic cortex contributes to impaired extinction memory and traumatic stress susceptibility in female rats, offering insight into the neurobiological mechanisms underlying vulnerability to stress-related disorders.

Background: Sleep, a core circadian rhythm, maintains physiological homeostasis. Its dysfunction links to neuropsychiatric disorders. Clinically, poor sleep impairs positive emotions and enhances negative emotion susceptibility, but the mechanism remains unclear, potentially involving circadian clock genes and neuroinflammatory pathways.

Methods: Divide the male C57BL/6J mice into the following five groups: Non-sleep deprivation (SD) control (CON), sleep recovery 14-day after SD 7-day (SD7R14), sleep recovery 21-day after SD 7-day (SD7R21), sleep recovery 14-day after SD 14-day (SD14R14), and sleep recovery 21-day after SD 14-day (SD14R21). Behavioral tests evaluated anxiety-like behaviors, fear and andanhedonia. Histological staining observed neuronal morphology in the medial prefrontal cortex (mPFC), and RT-qPCR was employed to measure mRNA levels of circadian clock genes, Silent information regulator 6 (Sirt6), High mobility group box-1 (Hmgb1), and inflammatory factors.

Results: SD induces time-dependent anxiety-like behaviors (reduced exploratory activity in elevated mazes), anhedonia (decreased sucrose preference), and fear behaviors (prolonged immobility in forced swim and tail suspension tests). Histological analysis reveals reversible neuronal damage in the mPFC, with complete recovery observed after 21 days of sleep restitution. Molecular analyses show dysregulation of the muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (Bmal1) and circadian locomotor output cycles kaput (Clock) circadian pathway and activation of the Sirt6/Hmgb1 inflammatory axis, leading to proinflammatory cytokine release (TNFα, IL1β, COX-2, IL6), with partial recovery after sleep restoration.

Conclusion: SD for 7-day or 14-day may impair emotional behaviors by disrupting the RNA expression of clock genes and the Sirt6/Hmgb1 inflammatory axis, while sleep recovery for 14-day or 21-day can partially reverse this impairment.