Myelination is a crucial process in the nervous system. This study aimed to evaluate the progression of myelin sheath development in different brain regions of neonatal rats at distinct developmental stages using Chemical Exchange Saturation Transfer (CEST) 7-T MRI. Male SD rats of different ages (3 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months) were selected for the study. Advanced in vivo MRI experiments were conducted using a 7-T MRI scanner. Custom MatLab scripts were employed to generate MR images and process the data. Myelin staining was used to assess myelin distribution in various brain regions. Statistical analysis was performed using repeated measures multivariate analysis of variance (MANOVA) and Spearman's rank correlation. The progression of myelination was significantly different in different brain regions (F(5, 30) = 3.34, P < 0.05), with the corpus callosum showing an accelerated rate of myelination. Within the first month alone, there was an increase of 46.1% in myelination (t(35) = 2.29, P < 0.05). The hypothalamus and internal capsule exhibited a more gradual yet consistent increase in myelination over the two-month period, with increases of 47.1% (t(35) = 2.27, P < 0.05) and 39.8% (t(35) = 2.59, P < 0.05), respectively. A substantial positive correlation was found between the MRI-based and histological measurements of myelination (r = 0.31, P < 0.05). This study demonstrates the potential of CEST 7-T MRI as a non-invasive tool for assessing myelination progression and provides insights into the differential myelination rates across various brain regions during early development.

The ocular vestibular evoked myogenic potential (oVEMP) is a measure of otolith function. The initial n10 peak follows a contralateral pathway from ipsilateral utricle to contralateral inferior oblique muscle. Following the n10, a series of positive and negative waves are elicited in the inferior oblique, but their characteristics and generators are unknown. This paper therefore investigated the latency, amplitude, and laterality of these late peaks in patients with hearing or vestibular loss compared to healthy volunteers. oVEMPs were elicited to bone-conducted (BC) square wave pulses and air-conducted (AC) clicks in 63 healthy volunteers, 15 patients with profound hearing loss (HL), 45 patients with unilateral vestibular loss (uVL), and 10 patients with bilateral vestibular loss (bVL). In healthy volunteers, up to 5 peaks and troughs were elicited to BC bilaterally. The first two peaks were largest, and amplitude decreased linearly thereafter. In healthy volunteers stimulated with AC clicks and patients with uVL stimulated with either stimulus, the first 2-3 oVEMP waves were significantly larger on the side opposite the healthy/stimulated ear, while the later waves were smaller and had similar amplitude bilaterally. All peaks were absent stimulating ears with no measurable vestibular function. Late peaks were elicited in patients with intact vestibular function regardless of hearing status, demonstrating the vestibular origin of all peaks. Like the clinical n10-p15 waves, the second waves followed a dominant contralateral pathway, while waves 3 onwards appear to have a separate origin and may represent bilateral projections to the extra-ocular muscles.

The N-methyl-D-aspartate (NMDA) receptors are related to the various functioning of the nervous system. It has been shown that the NR2B subunit plays an important role in neurological hypoxic/ischemic diseases by regulating NMDA receptor function. NR2B tyrosine phosphorylation is also an important regulatory mechanism for NMDA receptor function. However, the mechanism of NR2B tyrosine phosphorylation in hypoxic/ischemic injury is still unclear. Therefore, in the present study, we aimed to further clarify the changes in NR2B tyrosine phosphorylation in hypoxic/ischemic damage in the brain and its relationship with neuronal survival under hypoxic/ischemic conditions. Four types of NR2B tyrosine site mutants (Tyr → Phe at 1252, 1336, and 1472, and all three mutations together, named Y1252F, Y1336F, Y1472F, and Triple) and wild-type plasmids were transfected into HT22 cells. The cells were then exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). NR2B, cell apoptosis-related molecules, and neuronal survival factor CREB-related signaling proteins (CaMKII, ERK, Akt) were measured. Cell viability was assessed using the CCK-8 assay. Cell apoptosis and cell cycle were evaluated using flow cytometry. The death ratio of HT22 cells under OGD conditions was further tested using a live cell analysis platform. The viability of HT22 cells in the Y1252F, Y1336F, Y1472F, Triple mutants, and wild-type groups was elevated. Compared to the wild-type, western blotting and real-time PCR showed that Y1252F, Y1336F, Y1472F, and Triple mutants downregulated the expression of apoptosis factors and upregulated anti-apoptosis factors in the OGD/R model. Flow cytometry and cell cycle analysis demonstrated that Y1252F, Y1336F, Y1472F, and Triple mutants reduced the apoptosis rate. The percentage of cells in the S phase decreased significantly. Live cell analysis illustrated that the Y1252F, Y1336F, Y1472F, and Triple mutants contributed to HT22 cell survival under OGD conditions. Additionally, the Y1252F, Y1336F, Y1472F, and Triple mutants activated the survival signaling pathway. Furthermore, compared to the control group (without plasmid), only the Y1336F, Y1472F, and Triple mutants groups showed significant differences in the above tests. The tyrosine phosphorylation of NR2B at Y1336 and Y1472 plays key roles in hypoxic/ischemic injury. These phosphorylation sites may be potential targets for hypoxic/ischemic neural protection.

Gentamicin is a bactericidal aminoglycoside antibiotic that broadly targets Gram-negative microbes. Both human and animal studies have shown that administration of gentamicin is ototoxic by several routes of administration and results in sensorineural hearing loss due to damaged hair cell at the base of the cochlea. However, gentamicin is also administered intranasally to treat sinusitis in humans, but no animal studies have examined ototoxicity of gentamicin administered via this route. We hypothesized that intranasal irrigation of gentamicin will result in ototoxicity and impaired auditory function similar to systemic delivery. We investigated this hypothesis in Sprague-Dawley rats that received intranasal irrigations of gentamicin or saline from postnatal day (P) 21-31. We examined auditory function by assessing brainstem auditory evoked potentials in response to both broadband clicks and pure tone-pips (4, 8, 16, 24 and 32 kHz) on P41. We found significant changes in auditory function in gentamicin-exposed animals. Specifically, gentamicin-exposed animals had significantly higher thresholds in response to both clicks and tone-pips. In response to broadband clicks, there were no changes in latency for waves I through IV. However, we found significantly longer wave and interwave latencies for all waves in response to the 24 kHz tone-pip. Together, these findings suggest that intranasal administration of gentamicin results in impaired auditory function consistent with other routes of delivery.

Subclinical neck pain (SCNP) is a subset of the recurrent neck pain population for which individuals have not received treatment. Individuals with SCNP have been shown to have altered cerebellar processing. The cerebellum integrates sensorimotor information to refine and update internal models necessary for reaching movements. The impact of SCNP on sensorimotor integration and motor behavior has not been fully elucidated in the context of goal-directed reaching movements. Therefore, our study investigated the role of SCNP on these processes by comparing upper limb reaching movements to controls with the dominant and non-dominant hands using light and heavy styli in the vertical plane. The results show that those with SCNP have quicker reaction times and end their primary movement closer to the target compared to controls. This is likely to allow for greater central visual processing, thus illustrating the tendency for those with SCNP to rely more on visual feedback in order to compensate for an altered body schema.

The controlled release of grasping forces underlies skilled dexterous interactions with objects. While declines in force generation and maintenance are well documented in people with Parkinson's disease (PwPD), limited data exist related to how PD impacts the motor control of grasping force release. The aim of this project was to determine how PD impacts grip force release relative to the generation and maintenance of force. It was hypothesized that PwPD would exhibit global deficits in force control relative to controls but would perform disproportionately worse during the controlled release of grip force. Ten PwPD and 10 age-matched controls completed a force-tracking paradigm requiring grip force generation, maintenance, and release. Compared to controls, PwPD were less accurate (i.e. less time within target range), had greater error (i.e. greater relative root mean squared error), and had more trial-to-trial variability in error during grip force release. Ongoing studies are examining the potential neural mechanism(s) underlying of force release impairments in PD, and the relationships between PD severity, manual dexterity, and force release declines.

Many motor tasks are comprised of sequentially linked action phases, as when reaching for, lifting, transporting, and replacing a cup of coffee. During such tasks, discrete visual, auditory and/or haptic feedback are typically associated with mechanical events at the completion of each action phase, as when breaking and subsequently making contact between the cup and the table. An emerging concept is that important sensorimotor control operations, that affect subsequent action phases, are centred on these discrete multisensory events. By predicting sensory feedback at the completion of action phases, and comparing with the actual feedback that arises, task performance can be continuously monitored. If errors are detected, the sensorimotor system can quickly respond with task-protective corrective actions. The aim of this study was to investigate how discrete multisensory feedback at the completion of action phases are used in these control operations. To investigate this question, 42 healthy human participants (both male and female) performed a visually guided sequential reaching task where auxiliary discrete visual, auditory and/or haptic feedback was associated with the completion of action phases. Occasionally however, this feedback was removed in one or two modalities. The results show that although the task was visually guided, its control was critically influenced by discrete auditory and haptic feedback. Multisensory integration effects occurred, that enhanced the corrective actions, when auditory feedback was unexpectedly removed along with haptic or visual feedback. This multisensory enhancement may facilitate the ability to detect errors during sequential actions and amplify task-protective corrective actions.

Although flexible and portable virtual reality technologies have simplified measuring participants' perception of acoustic space, their clinical adoption remains limited, often lacking ecological fidelity. In clinical practice, participants are typically instructed to remain still when testing sound localization, whereas head movements are crucial in daily life. Additionally, assessing spatial hearing extends beyond measuring accuracy to include meta-cognitive evaluations like perceived effort and confidence, which are rarely adopted. Our study hypothesized that allowing head movement during sound localization, compared to a static head condition, would reduce perceived listening effort and enhance confidence in normal hearing participants. Conducted across three audiology and otology hospital services in Northern Italy, the study involved personnel inexperienced with our VR equipment. This also tested the feasibility and usability of our VR approach in clinical settings. Results showed that head movements reduced subjective effort but did not significantly affect perceived confidence. However, during the active condition, participants reporting higher confidence exhibited less head movement and explored the space less. Similarly, those with less head movement reported lower listening effort. These findings underscore the importance of allowing natural posture to capture the full extent of spatial hearing capabilities and the value of including metacognitive evaluations in assessing performance. Our use of affordable, off-the-shelf VR equipment effectively measured spatial hearing in clinical settings, providing a flexible alternative to current static systems. This approach highlights the potential for more dynamic and comprehensive assessments in clinical audiology.

Memory intrusion is a characteristic of posttraumatic stress disorder manifesting as involuntary flashbacks of negative events. Interference of memory reconsolidation using cognitive tasks has been employed as a noninvasive therapy to prevent subsequent intrusive retrieval. The present study aims to test whether physical activity, with its cognitive demands and unique physiological effects, may provide a novel practice to reduce later involuntary retrieval via the reconsolidation mechanism. In addition, the study investigates the EEG representation of neural function in interpreting the interplay of intrusion and recognition. Eighty-seven participants were tested on successive sessions comprised encoding (Day 0), reconsolidation (24-hr) and priming retrieval (Day 7) in a between-subject design with random assignment to 3 different groups: whole-body exercise, sensorimotor engagement and sitting groups. Of the key results, when involuntary retrieval was subsequently triggered by relevant stimuli, reduced subjective recognition was observed, and working memory maintenance was shortened, indicated by shorter Negative Slow Wave duration. The study implicates the potential neurophysiological mechanism of cognitive and behavioral interventions, specifically those aimed at reducing intrusion frequency through the reconsolidation mechanism; these are proposed to facilitate accelerated recovery from involuntary memories.

Executive function (EF) is improved following a single bout of exercise and impaired when an individual experiences mental fatigue (MF). These performance outcomes have been linked to a bi-directional change in cerebral blood flow (CBF). Here, we sought to determine whether MF-induced by a sustained vigilance task (i.e., psychomotor vigilance task: PVT) is mitigated when preceded by a single bout of exercise. Participants completed 20-min single bouts of active exercise (cycle ergometry involving volitional muscle activation), passive exercise (cycle ergometry involving a mechanical flywheel) and a non-exercise control intervention. EF was assessed pre- and post-intervention via the antisaccade task. Following each intervention, a 20-min PVT was completed to induce and assess MF, and transcranial Doppler ultrasound of middle cerebral artery velocity (MCAv) was used to estimate intervention- and PVT-based changes in CBF. Active and passive exercise provided a post-intervention reduction in antisaccade reaction times; that is, exercise benefitted EF. Notably, however, frequentist and Bayesian statistics indicated the EF benefit did not mitigate MF during the PVT. As well, although exercise (active and passive) and the PVT respectively increased and decreased CBF, these changes were not correlated with behavioral measures of EF or MF. Accordingly, a postexercise EF benefit does not mitigate MF during a sustained vigilance task and a bi-directional change in CBF does not serve as a primary mechanism associated with EF and MF changes. Such results provide a framework for future work to explore how different exercise types, intensities and durations may impact MF.

The ability to seamlessly switch between different visuomotor mappings is critical for effective interactions in a dynamic environment. This experiment aimed to establish the contributions of implicit (unconscious) processes to the concurrent adaptation of one's reaches to two opposing, randomly switching, novel visuomotor mappings (i.e., dual visuomotor adaptation). 59 right-handed participants were divided into two groups, a Dual adaptation group and a Single adaptation group, and trained to reach when small visuomotor distortions were introduced. The Dual group trained to reach when cursor feedback was rotated (i) 20° clockwise (CW) relative to hand motion when a target was displayed in the left visual workspace and (ii) 20° counterclockwise (CCW) relative to hand motion when a target was displayed in the right visual workspace. The Single group trained to reach with just one 20° cursor rotation (CW or CCW) in both visual workspaces. Results revealed that all participants adapted their reaches to the distorted cursor feedback. For all groups, visuomotor adaptation arose implicitly, in the absence of explicit (conscious strategy) contributions. However, the Dual group demonstrated significantly less implicit adaptation than participants who trained with a Single CW distortion, even after additional reach training trials. Together, these results indicate a role for implicit processes in simultaneously updating one's reaches to two small visuomotor mappings.

Motor imagery and execution often indicate a similar trend in the temporal characteristics of movements. This finding supports the notion of functional equivalence, whereby imagery and execution use a common neural representation. However, there is comparatively limited evidence related to the spatial characteristics of movements; no doubt owing to the absence of an actual spatial trajectory during imagery. Therefore, we adapted the trajectory priming paradigm involving an obstacle, where the trajectory adopted in a trial (n) is directly contaminated by a previous trial (n-1). If imagery accurately represents the spatial characteristics, then we would predict a similar priming effect as execution. Participants completed a series of trial blocks under different imagery/execution protocols, where the test trial (n) comprised execution alone, while the previous trial (n-1) involved imagery or execution. Each block comprised pairs of trials with alternate or consistent presentations of a virtual obstacle (O) or no obstacle (N): N-N, N-O, O-N, O-O. For trial n-1 (imagery/execution), there was a more prolonged reaction and movement time for imagery compared execution. Most importantly for trial n (execution), there was an increase in early angular and peak deviation following an obstacle compared to no obstacle in trial n-1, but only when it was execution and not imagery. These findings suggest imagery holds a limited representation of the spatial characteristics, while functional equivalence may be limited to the temporal characteristics.

Paraxanthine (PXN) is the main metabolite of caffeine (CAF). PXN supplementation has been shown to increase measures of cognition, memory, reasoning, response time, and sustained attention; however, no preclinical study has compared the effects of PXN with those of CAF. The aim of this study was to compare the effects of PXN and CAF on memory and related biomarkers in rats. The effects of two different doses of PXN (PXN LOW, PXN HIGH), CAF (CAF HIGH), and a control group on cognition (escape latency in the Morris water maze test), neurotransmitters (acetylcholine, dopamine, and gamma-aminobutyric acid), and neurochemicals (BDNF, catalase, glutathione, and cyclic GMP) were analyzed from whole brain samples in young (8 weeks old) and aged (16 months old) rats. Compared to the control group, escape latency improved in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.05) in young animals, and in PXN HIGH and CAF HIGH in older animals (P < 0.001). PXN HIGH improved escape latency compared to CAF HIGH in both young (P < 0.001) and old animals (P = 0.003). BDNF levels increased in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.001), with PXN HIGH increasing BDNF to a greater extent compared to CAF HIGH (P = 0.03). PXN HIGH also significantly increased BDNF levels compared to PXN LOW (P < 0.001). All other neurotransmitters and neurochemicals significantly increased in the PXN HIGH and CAF HIGH groups compared to the control. In conclusion, PXN showed greater improvements in cognition and BDNF levels compared to CAF, further substantiating PXN as a nootropic with greater benefits compared to CAF.

The purpose of this study was to determine whether the intermittent adaptation to pelvis perturbation load enhances retention of improved weight transfer and generalization of motor skills from treadmill to overground walking, compared with effects of the continuous adaptation. Fifteen individuals with incomplete SCI participated in two experimental sessions. Each session consisted of (1) perturbed treadmill walking with either intermittent (i.e., interspersed 3 intervals of no perturbation) or continuous (no interval) adaptation to novel walking patterns induced by external pelvis perturbation and (2) instrumented treadmill walking and overground walking before, immediately, and 10-min post perturbed treadmill walking. The external pulling force was applied to the pelvis towards the lateral side while the leg touched the treadmill belt. Participants showed a retention of improved mediolateral weight transfer (P = 0.002) and of enhanced activation of hip abductor (P = 0.016) and calf muscles (P < 0.05) in the intermittent condition, whereas the continuous condition did not (P ≥ 0.05). After the perturbed treadmill walking practice, participants exhibited increased mediolateral weight transfer during overground walking (P = 0.04) and enhanced propulsion (P = 0.047) during the instrumented treadmill walking for the intermittent condition, whereas the continuous condition did not show significant changes (P ≥ 0.13). Further, the intermittent condition induced a greater increase in overground walking speed than the continuous condition did (P = 0.002). In conclusion, intermittent adaptation to the pelvis perturbation load during treadmill walking can promote retention and generalization of motor learning for improving walking and balance in people with incomplete SCI.

The aim of this study is to investigate the effect of induced excitation of the bottom-up pathways at the lateral elbow muscles on local muscle fatigue in the neck region in healthy participants. Eligible participants (n:55) were randomly allocated to an intervention group (n:28) or a control group (n:27). The fatigue of bilateral neck flexor(sternocleidomastoid) and extensor (upper trapezius) muscles was evaluated using surface electromyography, at baseline and immediately post-intervention during a neck flexor and extensor endurance test respectively. Excitation of the bottom-up pathways was performed at multiple lateral elbow muscles in the intervention group by using a temporal summation protocol of mechanical pain, and the pressure pain threshold was determined once in each of the multiple lateral elbow muscles in the control group. Linear mixed model analyses were performed for each outcome measure to evaluate changes over time and within- and between-group differences. No significant "group X time" interaction effects were detected for any of the outcome measures. Significant main effects for time was found for "amplitude over time" of the left upper trapezius (p:0.003) and right sternocleidomastoid muscle (p: 0.013), and for "amplitude changes" of the left upper trapezius muscle (p:0.021). Significant within-group changes were identified in some outcomes in the control group: increased "amplitude over time" of the right sternocleidomastoid muscle (p:0.024) and decreased "amplitude changes" of the left upper trapezius muscle (p:0.024), decreased "normalized median frequency slope over time" of the left UT (p: 0.013). There were no significant within-group changes in the intervention group. No significant between-group differences for any of the outcome measures were found. This study shows no effect of the induction of excitation of the bottom-up pathways at the lateral elbow muscles on the neck muscles' fatigue characteristics compared to a control intervention. Clinical Trial Number: NCT05146960. Date of Registration: December 7, 2021.

The possible cognitive effect of sense of agency (SoA) has attracted increasing attention. Previous findings suggest that SoA has an effect on action control, time perception, and memory. Here we investigated whether SoA can also influence decision-making. We conducted two experiments, in which we induced high or low predictability by manipulating the contingency between keypresses (action) and ball movements (effect), before assessing SoA and risk-taking (in Experiment 1); and induced both predictability and short or long time delay of action-effect, before assessing SoA, risk-taking, and intertemporal decision-making (in Experiment 2). Higher predictability increased SoA and promoted risk-taking, but did not impact intertemporal decision-making; Shorter delay increased SoA and promoted Larger-Later options, but did not impact risk-taking decision-making. While our findings suggest that some decision-making processes are affected by the same factors as SoA is, we did not find any evidence for any direct impact of SoA on decision-making.

The purpose of our study was to evaluate the accuracy with which classification algorithms could distinguish among standing postures based on center-of-pressure (CoP) trajectories. We performed a secondary analysis of published data from three studies: Study A) assessment of balance control on firm or foam surfaces with eyes-open or closed, Study B) quantification of postural sway in forward-backward and side-to-side directions during four standing-balance tasks that differed in difficulty, and Study C) an evaluation of the impact of two modes of transcutaneous electrical nerve stimulation on balance control in older adults. Three classification algorithms (decision tree, random forest, and k-nearest neighbor) were used to classify standing postures based on the extracted features from CoP trajectories in both the time and time-frequency domains. Such classifications enable the identification of differences and similarities in control strategy. Our results, especially those involving time-frequency features, demonstrated that distinct CoP trajectories could be identified from the extracted features in all conditions and postures in each study. Although the overall classification accuracy was similar using time-frequency features (~ 86%) for the three studies, there were substantial differences in accuracy across conditions and postures in Studies A and B but not in Study C. Nonetheless, the models were far superior to the published results with conventional metrics in distinguishing between the conditions and postures. Moreover, a Shapley Additive exPlanation analysis was able to identify the most important features that contributed to the classification performance of the models.

Recent studies highlight a persistent increase in subsequent injury risk following a sport-related concussion (SRC) despite clinical recovery. However, markers of persistent alterations in sensorimotor integration have yet to be identified. One possibility is that compensatory adaptation following SRC may only be unmasked during transient periods of high task complexity in specific sensorimotor circuits. The current study used short-latency afferent inhibition (SAI) to investigate the long-term sequelae of sport-related concussion (SRC) in different short-latency sensorimotor circuits converging in the motor cortex. Specific sensorimotor circuits sensitive to posterior-anterior current with a positive phase lasting 120µs (PA) and anterior-posterior current with a positive phase lasting 30µs (AP) were assessed using controllable pulse parameter transcranial magnetic stimulation (cTMS) while young adults with and without a history of SRC were at rest or responded to valid and invalid sensorimotor cues. SAI was quantified as the ratio of the motor-evoked potential (MEP) elicited by peripherally conditioned cTMS stimuli to the unconditioned MEP for each cTMS configuration. Individuals with a SRC history demonstrated persistent adaptation in AP SAI, but only in response to invalid cues. Persistent adaptation in AP SAI was not apparent at rest or during simple sensorimotor transformations in response to valid cues. PA SAI demonstrated similar responses at rest and in response to both valid and invalid cues, regardless of SRC history. AP-sensitive sensorimotor circuits may mark the long-term SRC sequelae and the increased susceptibility to momentary breakdowns in sensorimotor integration during periods of high cognitive-motor demands.

We conducted an fMRI study to investigate the neural basis of bimanual coordination, which is fundamental to upper extremity control. Considering bimanual movement as a combination of bimanual chord formation and sequence control, we hypothesized that the areas with the learning effect of both chord formation and sequence learning are critical in bimanual coordination. We adopted the serial reaction time task (SRTT) to test this hypothesis. Thirty-five healthy right-handed volunteers practiced visually cued bimanual SRTT, including the "mirror" and more complex "parallel" modes of random movements or repeating fixed sequences to separately depict the neural substrates of bimanual posture control for chord formation and those of sequence. Random movements' reaction time (RT) continuously declined, indicating learning of bimanual chord formation. The RT in the sequential condition declined more rapidly than in the random condition, confirming sequence learning. The parallel random conditions evoked a more prominent learning-related decrease of task-related activation in the left M1 and cerebellar vermis than the less difficult mirror random conditions. The left M1 showed learning-related enhancement of functional connectivity with the anterior cingulate cortex during the parallel random conditions compared with the mirror random conditions. Thus, the left M1, anterior cingulate cortex, and cerebellar vermis are related to learning bimanual chord formation. The left M1 and cerebellar vermis also showed sequence-specific learning-related activity increments more prominent in the parallel mode than in the mirror mode. Thus, the left M1 and cerebellar vermis are critical in the bimanual motor learning network.

Methamphetamine (METH) has well-documented long-term effects on the brain, including increased psychomotor activity and behavioral sensitization. However, its immediate effects on the brain's reward system following acute exposure, which may contribute to the development of addiction, are less understood. This study aimed to investigate the effects of acute METH on brain oscillations in the nucleus accumbens of C57BL/6 mice. Mice in the METH group received 5 mg/kg of METH for 5 days during the conditioning phase, followed by an 8-day abstinence period. Afterward, they underwent a 6-minute tail suspension test and were given a 1 mg/kg METH challenge. Local field potential (LFP) data were analyzed for percent total power, mean frequency indices, and phase-amplitude coupling (PAC) to assess the neural effects of METH exposure across these phases. A reduction in theta power was observed across the conditioning, abstinence, and challenge phases of METH exposure. The subsequent METH challenge enhanced gamma oscillations, and PAC analysis revealed a consistent theta-gamma coupling index during both the METH administration and challenge phases. It highlights the sensitivity of the reward system to intense, short-term drug exposure, providing new insights into how acute neural stimulation may contribute to the development of addictive behaviors, reinforcing the brain's vulnerability to drug-induced changes in neural circuitry.

Animal studies have shown that exposure of newborns to general anesthesia drugs can lead to neurodegenerative diseases and subsequent decline in learning and memory abilities. The neurotoxicity of general anesthesia drugs can also occur in the fetus. Therefore, in order to investigate the effect of the Long non-coding RNA(LncRNA)-LIN-microRNA(miRNA)-9-Dopamine receptor D2(DRD2) regulatory network on the development of the neuronal system after the inhalation of the anesthetic sevoflurane, RT-qPCR was used to detect the mRNA levels of LncRNA-LIN, miRNA-9, and DRD2. A dual-luciferase reporter system was used to detect the relationship between LncRNA-LIN and miRNA-9, and miRNA-9 and DRD2. Western blotting and immunofluorescence staining was employed to detect the protein levels of DRD2 and cleaved caspase-3. Flow cytometry was carried out to detect the number of apoptotic cells. The escape latency, swimming distance, and platform crossing times were analyzed using the Morris water maze. The results showed that, after treatment with sevoflurane, the mRNA levels of LncRNA-LIN and DRD2, the expression levels of the DRD2 protein, and the number of neuronal levels of DRD2 were significantly decreased, whereas the expression levels of miRNA-9 and the cleaved caspase-3 protein and neuronal apoptosis were significantly increased. miR-9 knockdown revealed that miRNA-9 regulated DRD2 expression and affected the function of mouse neuronal cells. In turn, LncRNA-LIN overexpression indicated that LncRNA-LIN regulated miR-9 and affected the function of mouse neuronal cells. The present results demonstrated that the LncRNA-LIN-miRNA-9-DRD2 regulatory network is involved in the effects of the inhalation anesthetic sevoflurane on neuronal system development.