Neuroscience Research最新文献

Anger transition is often abrupt. In this study, we investigated the mechanisms responsible for switching and modulating aggression levels. The cerebellum is considered a center for motor coordination and learning; however, its connection to social behavior has long been observed. Here, we used the resident-intruder paradigm in male mice and examined local field potential (LFP) changes, glial cytosolic ion fluctuations, and vascular dynamics in the cerebellar vermis throughout various phases of a combat sequence. Notably, we observed the emergence of theta band oscillations in the LFP and sustained elevations in glial Ca²⁺ levels during combat breakups. When astrocytes, including Bergmann glial cells, were photoactivated using channelrhodopsin-2, the theta band emerged and an early combat breakup occurred. Within a single combat sequence, rapid alteration of offensive (fight) and passive (flight) responses were observed, which roughly correlated with decreases and increases in glial Ca²⁺, respectively. Neuron-glial interactions in the cerebellar vermis may play a role in adjusting Purkinje cell excitability and setting the tone of aggression. Future anger management strategies and clinical control of excessive aggression and violent behavior may be realized by developing a therapeutic strategy that adjusts glial activity in the cerebellum.

Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia.

Although sleep is tightly regulated by multiple neuronal circuits in the brain, nonneuronal cells such as glial cells have been increasingly recognized as crucial sleep regulators. Recent studies have shown that microglia may act to maintain wakefulness. Here, we investigated the possible involvement of microglia in the regulation of sleep quantity and quality under baseline and stress conditions through electroencephalography (EEG)/electromyography (EMG) recordings, and by employing pharmacological methods to eliminate microglial cells in the adult mouse brain. We found that severe microglial depletion induced by the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX5622 (PLX) reversibly decreased the total wake time and the wake episode duration and increased the EEG slow-wave power during wakefulness under baseline conditions. To examine the role of microglia in sleep/wake regulation under mental stress, we used the acute social defeat stress (ASDS) paradigm, an ethological model for psychosocial stress. Sleep analysis under ASDS revealed that microglial depletion exacerbated the stress-induced decrease in the total wake time and increase in anxiety-like behaviors in the open field test. These results demonstrate that microglia actively modulate sleep quantity and architecture under both baseline and stress conditions. Our findings suggest that microglia may potentially provide resilience against acute psychosocial stress by regulating restorative sleep.

Recent studies have associated interoceptive awareness, the perception of internal bodily sensations, with a predictive mechanism of perception across all sensory modalities. According to the framework, volitional attention plays a pivotal role in interoceptive awareness by prioritizing interoceptive sensations over exteroceptive ones. Consequently, it is hypothesized that the presence of irrelevant stimuli would disrupt the attentional modulation and interoceptive awareness, which remains untested. In this study, we investigated if interoceptive awareness is diminished by unrelated auditory distractors to validate the proposed perceptual framework. A total of 30 healthy human volunteers performed the heartbeat counting task both with and without auditory distractors. Additionally, we measured participant’s psychophysiological traits related to interoception, including the high-frequency component of heart rate variability (HF-HRV) and trait interoceptive sensibility. The results showed that interoceptive accuracy, confidence, and heartbeat intensity decreased in the presence of distractor sound. Moreover, individuals with higher HF-HRV and a greater tendency to worry about bodily states experienced a more pronounced distractor effect on interoceptive awareness. These results provide support for the perceptual mechanism of interoceptive awareness in terms of the predictive process, highlighting the impact of relative precision across interoceptive and exteroceptive signals on perceptual experiences.

The retrosplenial cortex (RSC) is a region involved in navigation. In this study, we investigated the role of the RSC in navigation in a large-scale environment where the destination is not visible from the current location. We used a large maze where the routes could be freely designed by inserting and removing plates. In Experiment 1, rats learned a specific route in the maze and then were tested with a shortcut route in addition to the learned route. The rats with RSC lesions utilized the shortcut faster than those in the control group. In Experiment 2, rats were initially trained to follow a specific route, and subsequently, we tested the effects of a small change in the environment on their route-following behavior. In the test, the rats with RSC lesions demonstrated more errors than those in the control group. This suggests that lesions in the RSC make navigation to a goal unstable. These findings suggest that the RSC may be involved in the ability to perform appropriate behavior at a segment on a learned route in a large-scale environment, which drives habitually following the learned route.

DSCAM (Down syndrome cell adhesion molecule) is a unique neuronal adhesion protein with extensively documented multifaceted functionalities. DSCAM also has interesting properties in vertebrates and invertebrates, respectively. In Drosophila species, particularly, Dscam exhibits remarkable genetic diversity, with tens of thousands of splicing isoforms that modulate the specificity of neuronal wiring. Interestingly, this splice variant diversity of Dscam is absent in vertebrates. DSCAM plays a pivotal role in mitigating excessive adhesion between identical cell types, thereby maintaining the structural and functional coherence of neural networks. DSCAM contributes to the oversight of selective intercellular interactions such as synaptogenesis; however, the precise regulatory mechanisms underlying the promotion and inhibition of cell adhesion involved remain unclear. In this review, we aim to delineate the distinct molecules that interact with DSCAM and their specific roles within the biological landscapes of Drosophila and vertebrates. By integrating these comparative insights, we aim to elucidate the multifunctional nature of DSCAM, particularly its capacity to facilitate or deter intercellular adhesion.