Loss of dopaminergic (DA) neurons leads to Parkinson's disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca²⁺channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. Store depletion that activates TRPC1, via STIM1, inhibits the frequency and amplitude of the rhythmic activity in DA neurons of wild-type, but not in TRPC1^−/−, mice. Similarly, TRPC1^−/−substantia nigra neurons showed increased L-type Ca²⁺currents, decreased stimulation-dependent STIM1-Ca_v1.3 interaction, and decreased DA neurons. L-type Ca²⁺currents and the open channel probability of Ca_v1.3 channels were also reduced upon TRPC1 activation, whereas increased Ca_v1.3 currents were observed upon STIM1 or TRPC1 silencing. Increased interaction between Ca_v1.3-TRPC1-STIM1 was observed upon store depletion and the loss of either TRPC1 or STIM1 led to DA cell death, which was prevented by inhibiting L-type Ca²⁺channels. Neurotoxins that mimic Parkinson's disease increased Ca_v1.3 function, decreased TRPC1 expression, inhibited Tg-mediated STIM1-Ca_v1.3 interaction, and induced caspase activation. Importantly, restoration of TRPC1 expression not only inhibited Ca_v1.3 function but increased cell survival. Together, we provide evidence that TRPC1 suppresses Ca_v1.3 activity by providing an STIM1-based scaffold, which is essential for DA neuron survival.SIGNIFICANCE STATEMENTCa²⁺entry serves critical cellular functions in virtually every cell type, and appropriate regulation of Ca²⁺in neurons is essential for proper function. In Parkinson's disease, DA neurons are specifically degenerated, but the mechanism is not known. Unlike other neurons, DA neurons depend on Ca_v1.3 channels for their rhythmic activity. Our studies show that, in normal conditions, the pacemaking activity in DA neurons is inhibited by the TRPC1-STIM1 complex. Neurotoxins that mimic Parkinson's disease target TRPC1 expression, which leads to an abnormal increase in Ca_v1.3 activity, thereby causing degeneration of DA neurons. These findings link TRPC1 to Ca_v1.3 regulation and provide important indications about how disrupting Ca²⁺balance could have a direct implication in the treatment of Parkinson's patients.

Aims: General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.Methods: Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst‐suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.Results: We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5‐HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5‐HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.Conclusion: Our results demonstrate that 5‐HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5‐HT 1A and 2C receptors.

Objective: The goal of the present research was to evaluate the effectiveness of physical exercise intervention in enhancing psychological well-being and decreasing symptoms of depression among college students, adopting a systematic review and meta-analysis. Methodology: The study was performed by searching four databases (PubMed, Embase, Web of Science, and the Cochrane Library) to determine randomized controlled trials (RCTs) exploring the impacts of physical exercise therapies among college students with symptoms of depression. The sequential execution of a meta-analyses, subgroup analyses, and publication bias analyses was accomplished utilizing the software package RevMan version 5.3. Results: There were eight articles included. This research demonstrated a significant impact (d = −0.75, P < 0.05), indicating that physical exercise has a substantial impact on decreasing or mitigating depression. The subgroup analyses revealed that interventions involving physical exercise workouts lasting 12 weeks or longer (d = −0.93, P < 0.05), with physical exercise sessions lasting between 30 and 60 min (d = −0.77, P < 0.05), and with physical exercise performed minimum of three times a week (d = −0.90, P < 0.05) were the most effective in reducing symptoms of depression. Conclusion: Physical exercise interventions have a beneficial impact on reducing depression among college students. The optimal mode was discovered to be college students participating in each session for a duration of 30 to 60 min, at least three times per week, and for more than 12 weeks. College students are encouraged to cultivate a consistent and long-term physical exercise routine to sustain their physical and mental health.

Neurotensin (NT) is a 13-amino acid peptide and serves as a neuromodulator in the brain. Whereas NT has been implicated in learning and memory, the underlying cellular and molecular mechanisms are ill-defined. Because the dentate gyrus receives profound innervation of fibers containing NT and expresses high density of NT receptors, we examined the effects of NT on the excitability of dentate gyrus granule cells (GCs). Our results showed that NT concentration dependently increased action potential (AP) firing frequency of the GCs by the activation of NTS1 receptors resulting in the depolarization of the GCs. NT-induced enhancement of AP firing frequency was not caused indirectly by releasing glutamate, GABA, acetylcholine, or dopamine, but due to the inhibition of TASK-3 K⁺ channels. NT-mediated excitation of the GCs was G protein dependent, but independent of phospholipase C, intracellular Ca²⁺ release, and protein kinase C. Immunoprecipitation experiment demonstrates that the activation of NTS1 receptors induced the association of Gα_q/11 and TASK-3 channels suggesting a direct coupling of Gα_q/11 to TASK-3 channels. Endogenously released NT facilitated the excitability of the GCs contributing to the induction of long-term potentiation at the perforant path-GC synapses. Our results provide a cellular mechanism that helps to explain the roles of NT in learning and memory.

Background: Awake craniotomy (AC) has become gold standard in surgical resection of gliomas located in eloquent areas. The conscious sedation techniques in AC include both monitored anesthesia care (MAC) and asleep-awake-asleep (AAA). The choice of optimal anesthetic method depends on the preferences of the surgical team (mainly anesthesiologist and neurosurgeon). The aim of this study was to compare the difference in physiological and blood gas data, dosage of different drugs, the probability of switching to endotracheal intubation, and extent of tumor resection and dysfunction after operation between AAA and MAC anesthetic management for resection of gliomas in eloquent brain areas. Methods: Two-hundred and twenty-five patients with super-tentorial tumor located in eloquent areas underwent AC from 2009 to 2021 in Xijing Hospital. Forty-one patients underwent AAA technique, and the rest one-hundred eighty-four patients underwent MAC technique. Anesthetic management, dosage of different drugs, intraoperative complications, postoperative outcomes, adverse events, extent of resection and motor, and sensory and language dysfunction after operation were compared between MAC and AAA. Result: There was no significant difference in gender, KPS score, MMSE score, glioma grade, type, and growth site between the patients in the two groups, except the older age of patients in MAC group than that in AAA group. During the whole process of operation, there were greater pulse pressure difference (P = 0.046), shorter operation time (P = 0.039), less dosage of remifentanil (P = 0.000), more dosage of dexmedetomidine (P = 0.013), more use of antiemetics (81%, P = 0.0067), lower use of vasoactive agent (45.1%, P = 0.010), and lower probability of conversion to general anesthesia (GA, P = 0.027) in MAC group than that in AAA group. Blood gas analysis showed that PetCO2 (P = 0.000), Glu concentration (P = 0.000), and PaCO2 (P = 0.000) were higher, but SPO2 (P = 0.002) and PaO2 (P = 0.000) were lower in MAC group than that in AAA group. In the postoperative recovery stage, compared with that of AAA group, the probability of dysfunction in MAC group at 1, 3, 5, and 7 days after operation was lower, which were 27.8% vs 53.6% (P = 0.003), 31% vs 68.3% (P = 0.000), 28.8% vs 63.4% (P = 0.000), and 25.6% vs 58.5% (P = 0.000), respectively. Conclusion: Compared with AAA, it seems that MAC has more advantages in the management for resection of gliomas in eloquent brain areas, and MAC combined with multiple monitoring such as cerebral cortical mapping, neuronavigation, and ultrasonic detection is worthy of popularization for the resection of gliomas in eloquent brain areas.

The investigation of cognitive functions in response to high-altitude exposure has garnered increasing scientific interest. However, it remains unclear whether cognitive abilities are selectively impaired or what are the trends of the function. In this study, we examined the effects of acute exposure to 3800 m on cognition among 20 lowlanders (27.9 ± 3.08 years; 18 males) for 1 week. Cognitive functions, physiological parameters, various questionnaires, and electroencephalogram (EEG) data were assessed at 400 m (D0) and during the acute phase at 3800 m (D1, D2, D3, D5, D7). A control group consisting of 23 subjects (26.5 ± 3.17 years; 21 males) underwent identical assessments at 400 m. Our findings indicate that within two days following ascent to 3800 m, nearly all cognitive indicators exhibited impairment, but gradually improved from the 3rd day and largely recovered to the plain level on the 5th to 7th day. EEG frequency analysis also revealed significant alterations, relative power in the delta band decreased markedly by D7 compared with D0, while theta and alpha bands showed the opposite trends. Correlational analyses between EEG features and cognitive functions revealed that relative power in the delta band exhibited a negative correlation with most cognitive measures, while relative power in the theta and beta bands predominantly demonstrated positive correlations. We conclude that most cognitive functions exhibit a pattern characterized by initial decline followed by recovery at 3800 m-an observation closely linked to observed EEG changes. These findings provide valuable insights into cognitive function and EEG performance at high altitudes.