Behavioral and Brain Functions最新文献

Background: Mild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understanding of genetic contributions, particularly the role of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, remains limited. This study aimed to characterize acute effects of repetitive mTBI (rmTBI) in rats with the Val68Met SNP, the rodent equivalent of the human Val66Met, focusing on behavioral, fluid biomarker, and histological changes.

Methods: Using a closed-head injury model, rats underwent five mTBIs over consecutive days. Behavioral assessments included sensorimotor function, anxiety-like behavior, spatial learning and memory, and nociceptive response. Plasma neurofilament light (NfL) levels served as a biomarker of axonal injury and immunohistochemistry evaluated microglial activation.

Results: Sensorimotor deficits and increased anxiety-like behavior were found in rats with rmTBI, but these changes were not affected by sex or genotype. Plasma NfL levels were higher in rmTBI compared with sham rats, with levels greater in female rmTBI when compared with male rmTBI rats. Microglial activation was observed in the hypothalamus of injured rats, but was not influenced by genotype or sex.

Conclusions: While the Val68Met SNP did not significantly influence acute responses to rmTBI in this study, further investigation into alternative functional and pathophysiological outcomes, as well as long-term effects, is required.

Background: Neuronal plasticity within the basolateral amygdala (BLA) is fundamental for fear learning. Metaplasticity, the regulation of plasticity states, has emerged as a key mechanism mediating the subsequent impact of emotional and stressful experiences. After mRNA knockdown of synaptic plasticity-related TrkB, we examined the impact of chronically altered activity in the rat BLA (induced metaplasticity) on anxiety-like behavior, fear memory-related behaviors, and neural plasticity in brain regions modulated by the BLA. These effects were investigated under both basal conditions and following exposure to acute trauma (UWT).

Results: Under basal conditions, TrkB knockdown increased anxiety-like behavior and impaired extinction learning. TrkBKD also reduced LTP in the vSub-mPFC pathway but not in the dentate gyrus. Compared with those of control animals, acute trauma exposure led to increased anxiety-like behavior and impaired extinction learning in both the trauma-exposed group (CTR-UWT) and the trauma-exposed group on the background of TrkB knockdown (TrkBKD-UWT). However, the deficit in extinction learning was more pronounced in the TrkBKD-UWT group than in the CTR-UWT group. Accordingly, TrkBKD-UWT, but not CTR-UWT, resulted in impaired LTP in the vSub- mPFC pathway. Since LTP in this pathway is independent of BLA involvement, this result suggests that lasting intra-BLA-induced metaplasticity may also lead to transregional metaplasticity within the mPFC, as suggested previously.

Conclusions: Taken together, these findings reveal the dissociative involvement of BLA function, on the one hand, in anxiety, which is affected by the knockdown of TrkB, and, on the other hand, in extinction learning, which is more significantly affected by the combination of intra-BLA-induced metaplasticity and exposure to emotional trauma.

Background: Sleep deprivation significantly impairs cognitive function, which disrupts daily life. However, sex differences in these impairments are not well understood, as most preclinical studies primarily use male animals, neglecting potential differences between sexes. This study aims to investigate sex-specific differences in cognitive function under sleep deprivation using reward-based operant conditioning tasks.

Results: Sprague-Dawley rats were pre-trained on a lever-press task and subsequently divided into control and chronic sleep restriction (CSR) groups. The CSR group underwent 14 days of sleep restriction. After CSR modeling, rats were assessed using the open field test, retraining on the lever-pressing task, signal discrimination task, and extinction task to evaluate motor abilities, memory formation, learning, and cognitive flexibility. CSR significantly impaired task performance in both sexes, with rats requiring more time and exhibiting lower accuracy. In the signal discrimination task, male rats showed longer feeding latency and lower accuracy compared to females. CSR also specifically increased the frequency of operant responses in male rats. In the extinction task, CSR enhanced exploration time and frequency in both sexes, with females exhibiting significantly higher exploration frequencies than males. Biochemically, CSR induced sex-specific alterations, including elevated serum MDA and MAO levels in males and increased serotonin, dopamine, and epinephrine in both sexes. Although activation was observed in metabolites of the tryptophan-kynurenine pathway, sex differences were evident in the kynurenic acid metabolism levels in the prefrontal cortex.

Conclusions: CSR impairs cognitive function in both male and female rats, with significant sex differences observed. Male CSR rats exhibited impaired signal discrimination, while CSR impaired extinction learning in female rats. These impairments are accompanied by CSR-induced oxidative stress, neurotransmitter dysregulation, and disturbances in the tryptophan metabolic pathway. These findings underscore the importance of considering sex differences in understanding the effects of sleep deprivation on cognitive function and developing targeted intervention strategies.

Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.

Gene-environment interactions in the postnatal period have a long-term impact on neurodevelopment. To effectively assess neurodevelopment in the mouse, we developed a behavioural pipeline that incorporates several validated behavioural tests to measure translationally relevant milestones of behaviour in mice. The behavioral phenotype of 1060 wild type and genetically-modified mice was examined followed by structural brain imaging at 4 weeks of age. The influence of genetics, sex, and early life stress on behaviour and neuroanatomy was determined using traditional statistical and machine learning methods. Analytical results demonstrated that neuroanatomical diversity was primarily associated with genotype whereas behavioural phenotypic diversity was observed to be more susceptible to gene-environment variation. We describe a standardized mouse phenotyping pipeline, termed the Developmental Behavioural Milestones (DBM) Pipeline released alongside the 1000 Mouse Developmental Behavioural Milestones (1000 Mouse DBM) database to institute a novel framework for reproducible interventional neuroscience research.

Reward cues have long been considered to enhance creative performance; however, little is known about whether rewards can affect creative problem solving by manipulating states of flexibility and persistence. This study sought to elucidate the differential impacts of real versus hypothetical rewards on the creative process utilizing the Chinese compound remote association task. Behavioral analysis revealed a significantly enhanced solution rate and response times in scenarios involving real rewards, in contrast to those observed with hypothetical rewards. Electrophysiological findings indicated that hypothetical rewards led to more positive P200-600 amplitudes, in stark contrast to the amplitudes observed in the context of real rewards. These findings indicate a positive impact of real rewards on creative remote associations and contribute new insights into the relationship between rewards and creative problem solving, highlighting the crucial role of persistence/flexibility in the formation of creativity.

The large-conductance calcium- and voltage-activated potassium (BK) channels, encoded by the KCNMA1 gene, play important roles in neuronal function. Mutations in KCNMA1 have been found in patients with various neurodevelopmental features, including intellectual disability, autism spectrum disorder (ASD), or attention deficit hyperactivity disorder (ADHD). Previous studies of KCNMA1 knockout mice have suggested altered activity patterns and behavioral flexibility, but it remained unclear whether these changes primarily affect immediate behavioral adaptation or longer-term learning processes. Using a 5-armed bandit task (5-ABT) and a novel Δrepeat rate analysis method that considers individual baseline choice tendencies, we investigated immediate trial-by-trial Win-Stay-Lose-Shift (WSLS) strategies and learning rates across multiple trials in KCNMA1 knockout (KCNMA1^-/-) mice. Three key findings emerged: (1) Unlike wildtype mice, which showed increased Δrepeat rates after rewards and decreased rates after losses, KCNMA1^-/- mice exhibited impaired WSLS behavior, (2) KCNMA1^-/- mice displayed shortened response intervals after unrewarded trials, and (3) despite these short-term behavioral impairments, their learning rates and task accuracy remained comparable to wildtype mice, with significantly shorter task completion times. These results suggest that BK channel dysfunction primarily alters immediate behavioral responses to outcomes in the next trial rather than affecting long-term learning capabilities. These findings and our analytical method may help identify behavioral phenotypes in animal models of both BK channel-related and other neurodevelopmental disorders.

Playing video games, especially games with action-based mechanics, is correlated with better cognitive performance, yet these performance advantages may originate from intrinsic factors such as earlier life cognitive differences. We investigated whether gaming-cognition associations in a sample past young adulthood remain robust after accounting for adolescent cognitive functioning. Using data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; N = 1241, M_age = 33.3, %, age range = 28-51, Female = 52.9%), we compared cognitive performance of adult recreational gamers (40.6%) to non-gamers (59.4%) and between different types of gamers. Measures included processing speed, spatial reasoning, and working memory cognitive tasks, gaming status, and gameplay type engagement. The majority of gamer participants reported exclusively playing puzzle/strategy/life simulation games (53.0%) or action type games (33.1%); a smaller proportion reported playing both types of games (10.3%). Overall, gamers significantly outperformed non-gamers across most cognitive tasks (Cohen's d = 0.17-0.25), with limited evidence of a differential gameplay mechanic effect across tasks. Selection effects were evident whereby after adolescent IQ adjustment, gamer cognitive effects diminished by over 35% but persisted for spatial performance. Adolescent IQ predicted puzzle/strategy/life simulation preference but not action-type games, suggesting a selection effect. Our study replicates prior gaming findings and reveals that earlier life functioning contributes to adult gaming-cognition associations. Gamer-spatial associations are not fully attributable to intrinsic factors, and playing video games, regardless of a specific gameplay mechanic or genre, may represent a cognitively engaging lifestyle behavior that may benefit cognitive functioning, with implications for preserved cognition.

Background: Early life stress (ELS) during the stress hypo-responsive period (SHRP) alters the curiosity-like behavior later during adolescence. Previous studies have shown maternal separation (MS) stress-induced heightened curiosity and associated risk-taking behavior in the object retrieval task (ORT). However, the neural correlates of curiosity in adolescent rats predisposed to early life stress remain unexplored. Hence, the present study aimed to investigate the neural oscillatory patterns and network characteristics in the regions implicated in curiosity behavior, such as the Prelimbic cortex (PL), Nucleus Accumbens (NAc), and CA1 of the Hippocampus. The local field potentials data were analysed to understand the neural activity patterns in these areas during the risky zone crossing and object retrieval phase of the ORT in MS rats and compared with the normal control (NC) group.

Results: In comparison to NC, MS rats showed a reduction in the theta power at 8-12 Hz, beta power at 12-20 Hz, and gamma power at 20-40 Hz range in the PL during risky zone crossing time. MS rats also showed reduced cross-correlation between PL-CA1 and reduced theta coherence between NAc-CA1 during risky zone crossing. During the object retrieval phase, the MS rats showed reduced peak cross-correlation between PL-CA1 and PL-NAc. Behaviourally, MS rats displayed an increased preference for the curiosity platform and retrieved more hidden objects, thus accounting for a higher curiosity index than controls.

Conclusion: In summary, a reduced synchronization between the PL, NAc, and CA1 during the object retrieval task indicates how early MS stress during a critical developmental period impacts the limbic circuit connectivity. This corresponded with enhanced curiosity index in adolescent MS rats, predicting an altered intrinsic motivation and hence a higher susceptibility to substance use disorders during adolescence.