Behavioral and Brain Functions最新文献

Background: Depression involves abnormal neural oscillations. Photobiomodulation (PBM) modulates such oscillations but lacks behavioral electrophysiological mechanistic studies. We explored PBM's effects on hippocampal CA1 oscillations and phase-amplitude coupling (PAC) in a depression model.

Methods: Male C57BL/6J mice were randomly divided into saline, LPS (2 mg/kg i.p.), and LPS + PBM groups (n = 10/group for behavioral tests, n = 8/group for electrophysiology). LPS groups received lipopolysaccharide to induce neuroinflammation. The LPS + PBM group underwent 810 nm PBM (20 mW/cm², 12 min/day × 4 days) starting day 4 post-injection. Anxiety- and depression-like behaviors were assessed via open field, elevated plus-maze, and tail suspension tests. Wireless electrophysiology recorded CA1 local field potentials (LFP) during rest and behaviors. Oscillations and PAC were analyzed. Data are presented as mean ± SD; group differences were evaluated by one-way ANOVA with Bonferroni post-hoc correction and ɳ² effect sizes, with two-tailed p < 0.05 taken as statistically significant.

Results: PBM (20 mW/cm²) alleviated LPS-induced anxiety and depressive behaviors. Electrophysiologically, PBM restored resting-state δ power (LPS + PBM: 0.0499 ± 0.0282, LPS: 0.1491 ± 0.0887; p < 0.01) and enhanced δ-γ coupling (LPS + PBM: 2.049 ± 0.447, LPS: 0.230 ± 0.298; p < 0.05). During anxiety tasks, PBM suppressed γ power (LPS + PBM: 0.3709 ± 0.1569, LPS: 0.5165 ± 0.06896; p < 0.05) and strengthened δ-γ PAC (LPS + PBM: 0.741 ± 0.508 vs. LPS: 0.217 ± 0.218, p < 0.05). In depression tests, PBM normalized δ power (LPS + PBM: 0.0261 ± 0.0182, LPS: 0.1315 ± 0.0619; p < 0.001) and reduced γ power (LPS + PBM: 0.2848 ± 0.0921, LPS: 0.4067 ± 0.0892; p < 0.05). No significant PAC changes was observed during depression tasks.

Conclusion: PBM therapy ameliorates LPS-induced depression and anxiety behaviors while normalizing hippocampal CA1 oscillations and cross-frequency coupling. Its effects are state-dependent, modulating distinct frequency bands and PAC across rest and behavioral contexts, revealing potential electrophysiological therapeutic mechanisms.

Background: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and one of the leading causes of disability worldwide. Neuroinflammation is strongly implicated in the pathophysiology of MDD, suggesting that regulators of neuroinflammatory signaling are feasible therapeutic targets. The CTNND1 gene encodes a member of the armadillo protein family termed p120 (or catenin delta) that functions in cell-cell adhesion and signal transduction, including among immune cells, suggesting immunomodulatory activity.

Results: We report that systemic injection of the bacterial toxin lipopolysaccharide (LPS) induced depression-like behaviors in mice while concomitantly activating the neuroinflammatory NF-κB signaling pathway, upregulating interleukin (IL)-1β expression, and reducing p120 expression in the hippocampus. Moreover, shRNA-mediated knockdown of hippocampal p120 expression also activated the NF-κB signaling pathway, enhanced IL-1β expression, and induced the same depression-like behaviors. Similarly, both LPS treatment and p120 knockdown upregulated pNF-κB and IL-1β levels in pheochromocytoma-12 cells.

Conclusions: These findings suggest that p120 may function to prevent the development or expression of depressive symptoms by suppressing proinflammatory NF-κB-IL-1β signaling in the hippocampus. Targeting p120 may be a feasible therapeutic strategy to treat MDD.

Background: Morphine addiction is a growing problem with severe consequences. Interestingly, Insulin-like Growth Factor-1 (IGF-1), a hormone with the ability to modulate neural pathways and exert neuroprotective and regenerative properties, could emerge as a potential treatment. However, to the best of our knowledge, the role of IGF-1 in the extinction and reinstatement phases of morphine induced conditioned place preference (CPP) remains unexplored. Thus, this study aimed to investigate the behavioral and biochemical effects of intracerebroventricular (ICV) IGF-1 administration on extinction and reinstatement after morphine induced CPP and c-Fos expression in nucleus accumbens (NAc).

Methods: Rats were conditioned with morphine (5 mg/kg, subcutaneously). The study examined alterations in CPP scores after administering varying multiple doses of IGF-1 (5, 10, and 20 µg) daily during the extinction and reinstatement phases of CPP, or single 20 µg dose administration prior to the extinction or prior to the reinstatement phase. Following these procedures, c-Fos levels in the NAc were quantified using the ELISA method.

Results: The findings revealed that daily administration of IGF-1 at doses of 5, 10, and 20 µg resulted in a dose-dependent reduction in conditioning scores and shorter extinction period. Importantly, only the 20 µg attenuated morphine reinstatement significantly. Additionally, c-Fos levels, which increased following morphine exposure, were markedly reduced by IGF-1 administration across all phases.

Conclusion: This study demonstrates that IGF-1 administration could facilitates the extinction and attenuate the reinstatement of morphine-induced CPP, highlighting its potential as a therapeutic strategy in opioid addiction.

Background: Adverse psychiatric symptoms caused by cannabis are a significant concern, and Δ9-tetrahydrocannabinol (THC) has been identified as a key contributor to these symptoms. THC binds to cannabinoid type 1 receptors (CB1Rs), which are abundant in the brain and associated with cognition. The prefrontal cortex (PFC) is crucial for cognitive functions. However, the functions of CB1Rs in the PFC in cognition processes remain unclear. Here, we injected arachidonylcyclopropylamide (ACPA), a CB1Rs agonist, into the PFC of male C57BL/6J mice via the cannula and conducted cognitive tests, including the novel object recognition test and object location test (OLT).

Results: These tests assessed memory in three stages: acquisition, consolidation, and retrieval. ACPA was administered immediately before each stage, and its intra-PFC administration specifically impaired memory acquisition in the OLT. In addition, in vivo microdialysis revealed that ACPA reduced extracellular GABA levels within the PFC. Next, we produced an adeno-associated virus with a glutamic acid decarboxylase promoter and an hM3Dq-encording chemogenic activator to activate GABAergic neurons in the PFC. Subsequently, deschloroclozapine (DCZ), an hM3Dq agonist, restored the memory acquisition impaired by ACPA.

Conclusion: Our findings suggest that CB1Rs in the PFC are involved in memory acquisition through the regulation of GABA release, offering new insights into how cannabis use lead to cognitive impairment.

Background: The psychomotor vigilance task (PVT) is a cognitive test commonly used to measure sustained attention and vigilance in humans in healthy and diseased states. Here, we aimed to utilize a recently designed rat version of the PVT to assess potential cognitive enhancer effects of various pharmacological compounds in a natural model of age-related cognitive decline. Therefore, we treated aged rats (> 28 months old) with different doses of three approved Alzheimer's disease drugs: donepezil, galantamine, and memantine.

Results: Aged rats made significantly slower responses to the cue stimuli compared to young animals and fewer correct responses, mainly because of an increased number of missed trials (i.e., when the trial was not initiated by the rat). Donepezil improved the performance of aged rats by accelerating their responses at a dose of 0.03 mg/kg. However, galantamine treatment showed no beneficial effects on either reaction time or the number of correct trials. Furthermore, both donepezil (0.3 and 1.0 mg/kg) and galantamine (3.0 mg/kg) increased the reaction time and number of missed trials at high doses. Memantine did not affect the reaction time of aged rats, but it increased the number of correct responses at 0.1 and 0.3 mg/kg doses.

Conclusions: Here, we showed that PVT is suitable for addressing pharmacological effects on various cognitive domains in a single behavioral paradigm. Our findings also indicate that different cognitive enhancer compounds (even when their targets are thought to be the same) may differentially influence distinct cognitive domains and modulate task performance.

Multivariate neuroimaging studies have shown a functional dissociation between the temporal and frontoparietal cortices in action representation. However, it remains unclear to what extent this specificity is modulated by motor experience. To address this question, we employed functional magnetic resonance imaging-based multivoxel pattern analysis (MVPA). Neural activation patterns were compared between professional table tennis players (experts) and novices during the passive observation of action videos and the reading of corresponding action-related sentences. Specifically, to identify brain regions that decode perceptual-motor information, classifiers were trained and tested within the same stimulus modality (video or sentence). To identify brain regions supporting conceptual-level action decoding, classifiers trained on video stimuli were tested on sentence stimuli, and vice versa. The results revealed that, in experts, the left lateral posterior temporal cortex (LPTC) and anterior temporal lobe (ATL) supported crossmodal action representations, whereas the left superior parietal lobule (SPL) and precentral gyrus (PreCG) exhibited modality-specific representations, particularly in response to video-based stimuli. In novices, only the PreCG showed modality-specific representations for video stimuli. These findings suggest a functional dissociation across brain regions, with the temporal cortex involved in conceptual-level representations of actions andthe SPL associated with processing perceptual-motor features. While such representations were more prominent in experts for familiar actions, the PreCG showed modality-specific representations regardless of group. These results highlight potential group-level differences in the neural encoding of action-related information, which may reflect the influence of task familiarity or prior sensorimotor experience.

Epstein-Barr virus (EBV) has been extensively studied for its associations with autoimmune disorders, various cancers, and neurological diseases. Emerging evidence also links EBV to behavioral and neurophysiological disruptions, potentially mediated through interactions with host's immune and circadian systems. In this study, we investigated the effects of EBV and its DNA on the behavior of Drosophila melanogaster by examining its lifespan, activity, sleep, and circadian rhythms. Both EBV viral particles and EBV DNA showed distinct effects in terms of behavior and survival. Circadian function analysis showed disruptions in several circadian parameters in EBV-injected flies, whereas EBV DNA-injected flies displayed defects in sleep behavior. Our findings suggest that EBV may impact circadian mechanisms, thereby enhancing our understanding of the effects of viral infections on circadian and behavioral systems and establishing Drosophila as a valuable model for future studies on EBV and host physiology.

Background: To observe the effects of copper sulfate (CuSO₄)-induced copper loading on neurobehaviour, mitochondria-associated endoplasmic reticulum membranes (MAMs) and related regulatory proteins in the hippocampal CA1 region of Sprague-Dawley (SD) rats.

Methods: Forty SD male rats were randomly divided into control and copper loading groups of 20 rats each. The control group rats were fed with normal feed and water; rats in the copper loading group were fed high copper feed (containing 1g/kg of CuSO₄) and CuSO₄ deionized water (concentration of 0.185%). After 12 weeks of rearing, the morris water maze (MWM) task and novel object recognition (NOR) test were conducted to compare the neurobehavioral characteristics of the two groups of rats. Morphological changes of neuronal MAMs in the hippocampal CA1 region of copper-loaded rats were observed using a transmission electron microscope (TEM) and immunofluorescence double-labelling techniques. Western-blot analysis was used to detect the expression of MAMs proteins VDAC1, IP3R, GRP75 and Mfn2.

Results: The results revealed that rats in the copper-loading group had significantly prolonged escape latency and reduced number of platform crossings in the MWM task (p < 0.01). The percentage of novel objects explored (also known as the Discrimination Ratio, DR) and the discrimination index (DI) were significantly reduced in the NOR test (p < 0.01). In addition, electron microscopy shows increased disruption of neuronal endoplasmic reticulum (ER)-mitochondrion coupling in the hippocampal CA1 region of rats in the copper-loading group (p < 0.05), and the percentage of MAMs in mitochondrial circumference decreased (p < 0.05), the colocalization coefficients between the ER and mitochondria was significantly reduced (p < 0.05). Moreover, the protein expression levels of VDAC1, IP3R, and GRP75 in rat hippocampal tissue were detected to be significantly increased (p < 0.01), while the protein expression level of Mfn2 was significantly decreased (p < 0.01).

Conclusions: In this study, it is speculated that the neurobehavioral changes in rats may be related to the increased expression levels of the MAMs proteins VDAC1, IP3R, and GRP75, the reduced expression level of Mfn2, and the disruption of the structural integrity of MAMs in the hippocampal CA1 region of rats caused by copper loading.

Background: Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPP) has been associated with several neurodegenerative diseases, however, few studies have investigated the role of PHLPP in Parkinson's disease (PD). The present study aimed to answer this question through establishing a Parkinson's disease (PD) model using the Phlpp1-/- and wild-type (WT) mice and testing their behavioral as well as molecular changes.

Methods: MPTP was intraperitoneal injected into mice to generate a PD model. Neurobehavioral parameters, protein expression and inflammatory cytokines release were measured by the open filed test, the pole test, immunohistochemistry, immunoblotting, immunoprecipitation, and quantitative reverse transcription PCR.

Results: MPTP-induced neurobehavioral deficits were more significantly ameliorated in PHLPP-KO-MPTP mice compared to WT-MPTP mice. The survival rate of TH⁺ neurons in the PHLPP-KO-MPTP group was higher than that in the WT-MPTP group (66% vs. 38%). Additionally, PHLPP1 knockout in KO-MPTP mice markedly reduced levels of IL-1β, IL-6, TNF-α, and iNOS, and increased levels of TGF-β compared to those of WT-MPTP mice. Furthermore, PHLPP1 was found to bind to NLRP3 and that PHLPP1 knockout inhibited MPTP-induced expression of IL-1β and caspase-1 in substantia nigra of PD model mice.

Conclusion: Our results demonstrates that PHLPP1 knockout in PD model is positively associated with the survival of TH + neurons by suppressing inflammatory response in substantia nigra, suggesting that PHLPP1 plays a critical role in the development of PD.

Background: Visual selective attention can be categorized into top-down (goal-driven) and bottom-up (stimulus-driven) attention, with the fronto-parietal network serving as the primary neural substrate. However, fewer studies have focused on the specific roles of the right dorsolateral prefrontal cortex (DLPFC) and superior parietal lobule (SPL) in top-down and bottom-up attention. This study aimed to investigate the activity and connectivity of the right DLPFC and SPL in top-down and bottom-up attention.

Methods: Visual pop-out task mainly induces bottom-up attention, while the visual search task mainly induces top-down attention. Fifty-four participants completed the pop-out and search tasks during functional magnetic resonance imaging (fMRI) scanning. We used univariate analyses, multivariate pattern analyses (MVPA), and generalized psychophysiological interaction (gPPI) to assess activity and functional connectivity.

Results: Univariate analyses revealed stronger activation in the right DLPFC and SPL during the search > pop-out condition. The activation of the DLPFC was driven by its deactivation in the pop-out task, whereas the SPL showed significant activation in both tasks. MVPA demonstrated that activation patterns in the right DLPFC and SPL could distinguish between the pop-out and search tasks above chance level (0.5), with the right SPL exhibiting higher classification accuracy. The gPPI analyses showed that higher functional connectivity between the two seeds (right DLPFC and SPL) and bilateral precentral gyrus, left SPL, and right insula.

Conclusions: These results indicate that the right DLPFC and SPL showed stronger activity and connectivity under top-down versus bottom-up attention, allowing for neural representation of visual selective attention. This study provides evidence for understanding the role of the fronto-parietal network in visual selective attention.