Behavioral and Brain Functions最新文献

Background: Postoperative sleep disturbances are common and have been shown to exacerbate incisional pain by enhancing the central nervous system's excitability. However, the specific neural circuit mechanisms underlying the pain chronification induced by postoperative sleep deprivation remain largely elusive.

Methods: We established a model of postoperative pain by plantar incision with perioperative sleep deprivation 6 h/day for 3 consecutive days in male mice. The activity of the neurons in the paraventricular thalamus nucleus (PVT) and the locus coeruleus (LC) was assessed using immunofluorescence and fiber photometry. Viral tracing, immunofluorescence staining, chemogenetics, optogenetics, and fiber photometry were utilized to investigate the anatomical and functional connections of the neural circuit. Furthermore, chemogenetic and optogenetic manipulations, combined with behavioral tests, were employed to investigate the roles of various nuclei or neural circuits in the perioperative sleep deprivation-induced prolongation of postsurgical pain.

Results: Sleep deprivation prolonged the duration of postsurgical pain and increased the excitability of glutamatergic neurons in the PVT (PVT^Glu) and tyrosine hydroxylase-positive neurons in the LC (LC^TH). Viral tracing revealed a direct projection from LC^TH neurons to PVT^Glu neurons. Selective chemogenetic activation of the LC^TH-PVT^Glu pathway reduced sleep duration and replicated the pain-prolonging effects of sleep deprivation. Furthermore, viral tracing and morphology indicate that GABAergic neurons in the medial prefrontal cortex (mPFC^GABA) receive projections from the LC^TH-PVT^Glu pathway. We found that hypersensitivity was sustained by the activation of the LC^TH-PVT^Glu-mPFC after incision, while its chemogenetic inhibition reversed sleep deprivation mediated pain prolongation.

Conclusion: These findings indicate that brainstem-thalamocortical pathway mediates the sleep deprivation-induced prolongation of postoperative pain. This circuit may serve as a mechanistic link between disrupted arousal states and pain duration, representing a potential therapeutic target for managing postsurgical pain.

Background: Post-traumatic stress disorder (PTSD) disrupts neural pathways, increasing susceptibility to neurological disorders, including epilepsy. Stress-induced alterations in glutamatergic, GABAergic, and serotonergic systems influence seizure susceptibility. This study investigates seizure thresholds within a PTSD-relevant mouse model, evaluating the roles of these neurotransmitters.

Methods: Male NMRI mice were exposed to predator stress using Wistar rats. Seizure thresholds were assessed via electroshock tests at multiple post-stress intervals. Pharmacological interventions, diazepam, MK-801, and fluoxetine, were administered seven days post-stress. Hippocampal tissues were analyzed for GABA_A receptor α₁ subunit, NMDAR1, and 5-HT_1A receptor expression, as well as nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) protein levels, utilizing Western blot techniques.

Results: Predator stress significantly decreased seizure thresholds in a time-dependent manner, with the highest effect on day 7 (P < 0.0001). Treatment with diazepam (P < 0.05), MK-801 (P < 0.0001), and fluoxetine (P < 0.0001) reversed these effects, increasing seizure thresholds. Western blot analysis revealed reduced expression of GABA_Aα₁, NMDAR1, and 5-HT_1A receptors (P < 0.001). Additionally, NF-κB levels were elevated while ERK levels were reduced (P < 0.001).

Conclusion: This study shows that predator stress is associated with increased seizure susceptibility and with downregulation of hippocampal GABAAα1R and 5-HT1AR expression, together with enhanced NF-κB activation and reduced ERK signaling. Pharmacological modulation of GABAergic, glutamatergic, and serotonergic pathways reversed the stress-induced reduction in seizure threshold in this model, suggesting that these systems may contribute to stress-related seizure susceptibility.

Background: Electroacupuncture is widely accepted to treat pain related conditions, but detailed mechanisms remain unknown.

Objective: To explore cortical and subcortical subnuclei involved in electroacupuncture stimulation (EAS) analgesia by observing EAS's analgesic efficacy and c-fos expression changes, providing a basis for neural circuit research and clinical transcranial magnetic stimulation (TMS) therapy.

Design, setting, participants and interventions: A chronic inflammatory pain model was established using knee osteoarthritis (KOA). Bilateral Zusanli was selected for electroacupuncture intervention. Von Frey test, open field test, elevated plus maze, and tail suspension test, and immunohistochemical staining were performed.

Main outcomes measures: Changes in mechanical pain threshold and pain-related emotional behaviors and distribution of c-fos positive cells in cortical and subcortical nuclei.

Results: Electroacupuncture significantly increased mechanical pain thresholds in KOA model mice. KOA modeling caused c-fos downregulation in the motor cortex, insular cortex, secondary auditory cortex, dorsal peduncular cortex, temporal association cortex, caudate putamen, lateral septal nucleus, accumbens nucleus, and the anterior cortical amygdaloid area. Electroacupuncture at Zusanli reversed these changes, upregulating c-fos in abovementioned brain regions, and additionally upregulated c-fos expression in the granular insular cortex, extended amydala.

Conclusion: Inflammatory pain induces widespread inhibition of neuronal activity in cortical and subcortical nuclei. The core mechanisms of electroacupuncture analgesia may involve direct reversal of abnormal inhibition in the lateral septal nucleus, caudate putamen, accumbens nucleus, and the anterior cortical amygdaloid area and activation of the granular insular cortex, medial septal nucleus and the extended amygdala for pain information integration.

Background: Teams are inherently adaptive entities that continuously adapt to changes or disruptions in their tasks or environments. During collaboration, interbrain synchrony (IBS) emerges, reflecting the temporal alignment of neural activity between team members. Building on this, IBS has been proposed as a potential marker of teamwork, suggesting that IBS should be sensitive to changes in teamwork.

Purpose: The present study investigated whether IBS is sensitive to changes in teamwork. We hypothesized that disruptions in teamwork would be accompanied by alterations in IBS dynamics.

Methods: Ninety-eight healthy adults (mean age = 22.5 ± 3.22 years; 69 females, 65.1%) were assigned to forty-nine dyads. Each pair completed a 20-minute computer-based navigation task while their brain activity was simultaneously recorded using fNIRS hyperscanning. Dyads in the experimental group encountered an unexpected increase in task difficulty midway through the task, whereas those in the control group completed the task without disruption. We examined three features of IBS - its overall level, temporal slope trajectory, and the temporal recurrence patterns.

Results: Control analyses confirmed that IBS reliably emerged during the task (χ²(1) = 50.24, p < .001) and that the experimental manipulation successfully disrupted teamwork, as reflected in altered team behavioral responses in communication (χ²(1) = 8.48, p = 0.004) and performance (χ²(1) = 24.99, p < .001). Nevertheless, no evidence was found for disruption-related changes in IBS across the three features examined (all Time x Group interactions p > .05.

Conclusion: These findings raise the possibility that IBS may reflect a stable collective state rather than a reactive one, thereby challenging its interpretation as a direct marker of teamwork. Methodological considerations, including the operationalization of IBS, are also discussed as potential explanations for the lack of observed change in IBS.

Background: Excessive stress leads to injury and dysfunction, but the underlying mechanism remains unclear. As a human longevity gene, forkhead box O3a (FoxO3a) is a transcription factor that regulates various cellular processes, including the response to oxidative stress, apoptosis, and autophagy. This study aims to explore whether FoxO3a in the dentate gyrus (DG) of the hippocampus is involved in the formation of anxiety- and depressive-like behavior and cognitive impairment in stressed rats and to investigate the detailed mechanism.

Methods: This study was conducted using the 6-week chronic unpredictable stress (CUS) model. Before the stress treatment, we injected an adeno-associated virus (AAV) vector to overexpress FoxO3a specifically in the DG. Following the 6-week CUS treatment, a series of behavioral tests was conducted. Depression-like behavior was assessed using the sucrose preference test (SPT) and the open field test (OFT). The state of desperation was assessed with the forced swim test (FST) and tail suspension test (TST). Anxiety-like behavior was measured in the elevated plus maze (EPM) and OFT. Cognitive function was examined using the Y-maze test (Y-maze), novel object recognition test (NORT), and Morris water maze test (MWM). The level of reactive oxygen species (ROS) and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. The levels of inflammatory factors were detected by ELISA. Pathological injury in DG was observed using thionine staining. The expression levels of FoxO3a, brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), and proliferation marker Ki67 (Ki67) were determined using western blot.

Results: CUS leads to various abnormal changes, including anxiety- and depressive-like behavior, cognitive impairment, oxidative stress, neuroinflammation, neuropathological alterations in the DG, and decreased expression of FoxO3a, BDNF, PSD95, SYN, and Ki67. All these abnormal changes were significantly alleviated by targeted AAV-FoxO3a injection in the DG.

Conclusions: In conclusion, our study demonstrates that the downregulation of FoxO3a induced by CUS in the DG triggers oxidative stress and inflammatory response, inhibits cell proliferation, and induces abnormal synaptic plasticity, ultimately leading to anxiety- and depressive-like behaviors and cognitive impairment.

Background: The effect of olfactory bulb (OB) and olfactory epithelium (OE) electrical stimulation on epileptiform activity and seizure-induced impairment on synaptic plasticity and memory was investigated in anesthetized and freely-moving animals.

Methods: Male Wistar rats were anesthetized with urethane (1.5 g/kg). Stimulating electrodes were bilaterally placed in either the OB or the OE. Another electrode was placed in the CA1 area for recording epileptiform discharges (EDs) following a pentylenetetrazol (PTZ, i.v.) injection and evoked field potentials following Schaffer collateral stimulation. Subjects were divided into PTZ and control groups. Each group received a 1 Hz stimulation either in the OB (OBS) or the OE (OES). ED threshold and duration, and the ability to generate long-term potentiation (LTP) were assessed. Finally, the effect of OBS on acute PTZ-induced seizures and working memory was investigated in freely-moving animals. OBS significantly increased the ED threshold when applied at 250 µA and decreased ED duration when applied at 125 and 250 µA.

Results: Applying OES had a small effect on the ED threshold but significantly decreased ED duration when applied at 125 and 250 µA. Both OBS and OES mitigated the PTZ-induced increase in basal synaptic transmission. Meanwhile, OBS and OES significantly restored the LTP generation following PTZ injection in anesthetized rats. In addition, applying OBS in freely-moving animals reduced the seizure severity and restored working memory impairment.

Conclusions: OB and OE may be considered effective stimulation targets for the attenuation of epileptiform activity and seizure severity. In addition, both OBS and OES decreased the seizure-induced impairment in LTP generation.

Background: Regular physical activity (PA) confers numerous benefits to both peripheral and cerebral health, including enhanced cardiovascular and muscular function, as well as improved cognitive performance and neuroplasticity. The hippocampus, a brain region highly sensitive to the effects of PA, has been consistently shown to undergo structural enhancements with sustained exercise. However, the impact of physical detraining-the cessation or significant reduction of regular PA-on hippocampal structure remains largely unexplored, particularly in humans. This study aimed to investigate whether a 14-day period of voluntary exercise reduction leads to measurable structural changes in the hippocampus, and whether these changes are associated with anxiety symptomatology.

Results: Paired t-tests analyses did not reveal significant changes in hippocampal volume for the whole sample. However, multiple regression analyses on volume change including physical fitness index and degree of moderate and vigorous PA reduction as independent variables, revealed a significant decrease in hippocampal gray matter volume following detraining in individuals with greater MVPA reduction. Notably, pre and post-detraining state anxiety levels were lower in participants who showed larger reductions in hippocampal volume.

Conclusions: These findings suggest that even short-term interruptions in regular physical activity may prompt rapid structural changes in the hippocampus, modulated by the extent of detraining. The observed relationship between hippocampal volume reduction and decreased state anxiety points to stress regulation as a potential mechanism. Further research is warranted to explore the functional significance and potential reversibility of these neuroplastic changes.

Background: The cytosolic 5'-nucleotidase II (NT5C2) enzyme has been implicated in both psychiatric disorders and metabolic traits, but whether these associations reflect a shared biological basis remains unclear. Here we combined cross-species approaches to investigate how reduced NT5C2 function shapes behavior.

Results: In Drosophila melanogaster, neuronal knockdown of the ortholog dNT5B increased activity around light-dark transitions, reduced sleep fragmentation, and selectively suppressed food intake under satiated conditions. Moreover, analysis of mouse phenotyping data revealed that whole-body Nt5c2 knockout alters locomotor activity, sensorimotor gating, and anxiety-related behaviors. Finally, human variant-trait associations showed reproducible enrichment in both metabolic domains, including body composition and BMI, and neuro-psychiatric outcomes such as schizophrenia, smoking, and anxiety.

Conclusions: Together, these phenotypic findings indicate that NT5C2 is a conserved neuro-metabolic regulator, linking energy-related pathways to specific behavioral dimensions that may underlie its pleiotropic impact on psychiatric and metabolic risk.