Circadian neurogenetics and its implications in neurophysiology, behavior, and chronomedicine.

The circadian rhythm affects multiple physiological processes, and disruption of the circadian system can be involved in a range of disease-related pathways. The genetic underpinnings of the circadian rhythm have been well-studied in model organisms. Significant progress has been made in understanding how clock genes affect the physiological functions of the nervous system. In addition, circadian timing is becoming a key factor in improving drug efficacy and reducing drug toxicity. The circadian biology of the target cell determines how the organ responds to the drug at a specific time of day, thus regulating pharmacodynamics. The current review brings together recent advances that have begun to unravel the molecular mechanisms of how the circadian clock affects neurophysiological and behavioral processes associated with human brain diseases. We start with a brief description of how the ubiquitous circadian rhythms are regulated at the genetic, cellular, and neural circuit levels, based on knowledge derived from extensive research on model organisms. We then summarize the latest findings from genetic studies of human brain disorders, focusing on the role of human clock gene variants in these diseases. Lastly, we discuss the impact of common dietary factors and medications on human circadian rhythms and advocate for a broader application of the concept of chronomedicine.

Cognitive-Affective Functions of the Cerebellum.

The cerebellum, traditionally associated with motor coordination and balance, also plays a crucial role in various aspects of higher-order function and dysfunction. Emerging research has shed light on the cerebellum's broader contributions to cognitive, emotional, and reward processes. The cerebellum's influence on autonomic function further highlights its significance in regulating motivational and emotional states. Perturbations in cerebellar development and function have been implicated in various neurodevelopmental disorders, including autism spectrum disorder and attention deficit hyperactivity disorder. An increasing appreciation for neuropsychiatric symptoms that arise from cerebellar dysfunction underscores the importance of elucidating the circuit mechanisms that underlie complex interactions between the cerebellum and other brain regions for a comprehensive understanding of complex behavior. By briefly discussing new advances in mapping cerebellar function in affective, cognitive, autonomic, and social processing and reviewing the role of the cerebellum in neuropathology beyond the motor domain, this Mini-Symposium review aims to provide a broad perspective of cerebellar intersections with the limbic brain in health and disease.

Social memory deficit caused by dysregulation of the cerebellar vermis.

Social recognition memory (SRM) is a key determinant of social interactions. While the cerebellum emerges as an important region for social behavior, how cerebellar activity affects social functions remains unclear. We selectively increased the excitability of molecular layer interneurons (MLIs) to suppress Purkinje cell firing in the mouse cerebellar vermis. Chemogenetic perturbation of MLIs impaired SRM without affecting sociability, anxiety levels, motor coordination or object recognition. Optogenetic interference of MLIs during distinct phases of a social recognition test revealed the cerebellar engagement in the retrieval, but not encoding, of social information. c-Fos mapping after the social recognition test showed that cerebellar manipulation decreased brain-wide interregional correlations and altered network structure from medial prefrontal cortex and hippocampus-centered to amygdala-centered modules. Anatomical tracing demonstrated hierarchical projections from the central cerebellum to the social brain network integrating amygdalar connections. Our findings suggest that the cerebellum organizes the neural matrix necessary for SRM.

Limited expression of Nrf2 in neurons across the central nervous system.

Nrf2, encoded by the gene Nfe2l2, is a broadly expressed transcription factor that regulates gene expression in response to reactive oxygen species (ROS) and oxidative stress. It is commonly referred to as a ubiquitous pathway, but this generalization overlooks work indicating that Nrf2 is essentially unexpressed in some neuronal populations. To explore whether this pattern extends throughout the central nervous system (CNS), we quantified Nfe2l2 expression and chromatin accessibility at the Nfe2l2 locus across multiple single cell datasets. In both the mouse and human CNS, Nfe2l2 was repressed in almost all mature neurons, but highly expressed in non-neuronal support cells, and this pattern was robust across multiple human CNS diseases. A subset of key Nrf2 target genes, like Slc7a11, also remained low in neurons. Thus, these data suggest that while most cells express Nfe2l2, with activity determined by ROS levels, neurons actively avoid Nrf2 activity by keeping Nfe2l2 expression low.

Survival analysis of a comprehensive treatment strategy for internal carotid artery blowout syndrome by nasopharyngeal carcinoma.

OBJECTIVE: To retrospectively analyze the comprehensive treatment strategy for internal carotid artery blowout syndrome (CBS) by nasopharyngeal carcinoma (NPC). METHODS: Of the 311 patients of NPC with carotid artery blowout syndrome admitted at our center from April 2018 to August 2022, 288 were enrolled. RESULTS: The patients were divided into two groups: treatment group (266 cases) and control group (22 cases). After comprehensive treatment, the survival rate of the treatment group was significantly higher than that of the control group, especially within 6 months to the 1 year. Preventive intervention for CBS I type may have considerable benefits. And in the long run, this treatment strategy did not significantly increase the incidence of stroke in the treatment group. CONCLUSION: The comprehensive treatment strategy for ICA-CBS of patients with NPC significantly reduced the mortality of asphyxia due to epistaxis, reduced the incidence of CBS during nasal endoscopy, and finally improved survival rate.

Super-rational aspiration promotes cooperation in the asymmetric game with peer exit punishment and reward.

Super-rational aspiration induced strategy updating with exit rights has been considered in some previous studies, in which the players adjust strategies in line with their payoffs and aspirations, and they have access to exit the game. However, exit payoffs for exiting players are automatically allocated, which is clearly contrary to reality. In this study, evolutionary cooperation dynamics with super-rational aspiration and asymmetry in the Prisoner's Dilemma game is investigated, where exit payoffs are implemented by local peers. The results show that for different population structures, the asymmetry of the system is always contributive to the participation of the players. Furthermore, we show that under different exit payoffs, super-rationality and asymmetry are conductive to the evolution of cooperation.

Limited Expression of Nrf2 in Neurons Across the Central Nervous System.

Nrf2 is a broadly expressed transcription factor that regulates gene expression in response to reactive oxygen species (ROS) and oxidative stress. It is commonly referred to as a ubiquitous pathway, but this generalization overlooks work indicating that Nrf2 is essentially unexpressed in some neuronal populations. To explore whether this pattern extends throughout the central nervous system (CNS), we quantified Nrf2 expression and chromatin accessibility at the Nrf2 locus across multiple single cell datasets. In both the mouse and human CNS, Nrf2 was repressed in almost all mature neurons, but highly expressed in non-neuronal support cells, and this pattern was robust across multiple human CNS diseases. A subset of key Nrf2 target genes, like Slc7a11 , also remained low in neurons. Thus, these data suggest that while most cells express Nrf2, with activity determined by ROS levels, neurons actively avoid Nrf2 activity by keeping Nrf2 expression low.

The Relationship Between Serum 25-Hydroxyvitamin D Levels and Osteoporosis in Postmenopausal Women.

Background: Vitamin D status is indicated by serum 25-hydroxyvitamin D [25(OH)D] levels, and the positive effects of high levels of vitamin D on bone mineral density (BMD) have not been ascertained. Therefore, we performed a study to analyze the association between serum 25(OH)D levels and osteoporosis in postmenopausal women. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). Multiple logistic regression was used to explore the relationship between serum 25(OH)D and osteoporosis of total femur, femoral neck and lumbar spine, with stratified analyses for age (<65 and ≥65 years), BMI (<25, 25 to <30, ≥30 kg/m2) and survey months (winter months and summer months). Results: In total, 2058 participants were enrolled in our study. In the fully adjusted model, compared with serum 25(OH)D levels <50 nmol/L, the odds ratios (ORs) and 95% confidence intervals (CIs) of serum 25(OH)D 50-<75 nmol/L and ≥75 nmol/L were 0.274 (0.138, 0.544) and 0.374 (0.202, 0.693) in osteoporosis of total femur, 0.537 (0.328, 0.879) and 0.583 (0.331, 1.026) in osteoporosis of femoral neck, and 0.614 (0.357, 1.055) and 0.627 (0.368, 1.067) in osteoporosis of lumbar spine, respectively. The protective effect of high 25(OH)D was observed at all three skeletal sites in those ≥65 years of age, whereas it was observed only in the total femur in those <65 years of age. Conclusion: In conclusion, adequate vitamin D may reduce the risk of osteoporosis in postmenopausal women in the United States, especially in those aged 65 years and older. More attention should be given to serum 25 (OH) D levels to prevent osteoporosis.

'Y'-Shaped Palmar Common Digital Artery Interposition Bypass in the Treatment of an Infantile M2 Large Aneurysm and Literature Review.

OBJECTIVE: Both craniotomy and interventional embolization are difficult and risky to treat complex middle cerebral artery (MCA) aneurysms in infants. Trapping with revascularization is a therapeutic option for giant aneurysms that cannot be clipped or coiled alone. METHOD: We describe a technical method using revascularization with a natural Y-shaped palmar common digital artery interposition graft that provides a normal variation for a complex MCA aneurysm in an infant with intracerebral hemorrhage at 37 days of age. Conservative treatment was performed at that time. Seven months later, the patient was re-admitted to the hospital and was confirmed a large aneurysm in the M2 segment of the right MCA by cerebral angiography. A natural artery palmar common digital artery Y-graft was used as the graft and anastomosed to the M2 and both M3 trunks. RESULT: The symptoms improved after surgery, and the mRS score of the patient was 1 after 5 years of follow-up. CONCLUSION: The palmar common digital artery can be an option for intracranial revascularization bypass in complex intracranial aneurysms.

Association between age at menarche and bone mineral density in postmenopausal women.

BACKGROUND: Age at menarche (AAM) directly affects female estrogen levels, which play a vital role in bone metabolism. The exact relationship between bone mineral density (BMD) and AAM remains controversial. Thus, this study aimed to determine the association between AAM and lumbar spine (LS) BMD in postmenopausal women. METHODS: Our data were based on the National Health and Nutrition Examination Survey (NHANES) 2011-2018. AAM was divided into three categories including ≤ 12, 13-15, and ≥ 16 years, and the ≤ 12 years old category was used as the reference group. To examine the association between AAM and LS BMD, we used three weighted linear regression models, Model 1 (without adjustment), Model 2 (with adjustment for age, race, and body mass index [BMI]), and Model 3 (with adjustment for all covariates). RESULTS: This study included 1195 postmenopausal women aged 40-59 years. In the unadjusted model, a menarche age of ≥ 16 years compared with a menarche age of ≤ 12 years was associated with lower LS BMD (ß = - 0.083, 95% CI - 0.117, - 0.048, P < 0.001). After adjusting for potential confounding factors, there was still a negative correlation in model 2 (ß = - 0.078, 95% CI - 0.113, - 0.042, P < 0.001) and model 3 (ß = - 0.065, 95% CI - 0.096, - 0.033, P < 0.001). Moreover, this significant relationship persisted after excluding participants who used female hormones (ß = - 0.053, 95% CI - 0.089, - 0.016, P = 0.006). CONCLUSION: Our study found that postmenopausal women with a menarche age of ≥ 16 years had significantly lower LS BMD than that had by those with a menarche age of ≤ 12 years. As a result of this study, postmenopausal women with a late menarche age may have a higher risk of lumbar osteoporotic fractures and need better bone health care.

A suturable biohydrogel with mechanical matched property based on coating chitosan and polyethylene glycol shell for tissue patching.

The mechanical mismatch between soft hydrated tissues and sutures has become a common negative impact on wound healing process. A novel method of coating multilayer polymer shells is thus reported to improve the mechanical performance of hydrogel sutures. It is suitable for tissue patching and shows advantages of convenient, efficient, and biosafety. Specifically, a precursor hydrogel (Cu@CMC) consisted of carboxymethyl chitosan and copper modified by carbon dots was used as the inner sheath, and then bonding the precursor hydrogel sheath with toughening polyethylene glycol network by anchoring sites composited from rigid chitosan shell integrated a whole structure. Subsequently, the whole system was soaked with EtOH, and rapid dehydration of EtOH was used to accelerate the entanglement process between the two coatings by constricting the molecular chains. Finally, an ideal suture (Cu-fiber) with both toughness and rigidness was obtained. The data showed that the tensile strength and biosafety of the hydrogel sutures prepared by the new strategy were significantly improved, and the skin, liver and vessel of rodents can be sutured without secondary damage. Moreover, it can inhibit inflammation response and promote the healing process of skin wound, indicating that the Cu-fiber will become a great candidate for tissue patching.

Neuronal circuitry for recognition memory of object and place in rodent models.

Rats and mice are used for studying neuronal circuits underlying recognition memory due to their ability to spontaneously remember the occurrence of an object, its place and an association of the object and place in a particular environment. A joint employment of lesions, pharmacological interventions, optogenetics and chemogenetics is constantly expanding our knowledge of the neural basis for recognition memory of object, place, and their association. In this review, we summarize current studies on recognition memory in rodents with a focus on the novel object preference, novel location preference and object-in-place paradigms. The evidence suggests that the medial prefrontal cortex- and hippocampus-connected circuits contribute to recognition memory for object and place. Under certain conditions, the striatum, medial septum, amygdala, locus coeruleus and cerebellum are also involved. We propose that the neuronal circuitry for recognition memory of object and place is hierarchically connected and constructed by different cortical (perirhinal, entorhinal and retrosplenial cortices), thalamic (nucleus reuniens, mediodorsal and anterior thalamic nuclei) and primeval (hypothalamus and interpeduncular nucleus) modules interacting with the medial prefrontal cortex and hippocampus.

The Construction and Effect Analysis of Nursing Safety Quality Management Based on Data Mining.

Data mining belongs to knowledge discovery, which is the process of revealing hidden, unknown, and valuable information from a large amount of fuzzy application data. The potential information revealed by data mining can help decision-makers adjust market strategies and reduce market risks. The information mined can be the discovery of a particular study and little known, which must be based on the principle of truth. Nursing safety means that during nursing work, the nursing staff must strictly follow the nursing system and operating procedures, accurately execute doctor's orders, implement nursing plans, and ensure that patients get physical and mental safety during treatment and recovery. This paper aims to explore the construction of nursing safety quality management system and its effect analysis based on data mining. It is hoped that improvements in hospital nursing processes will provide better nursing services for patients using data mining techniques. This paper uses the FP algorithm to mine the data set and generates frequent itemsets, proposes and implements the association rule mining algorithm, and obtains the association rules with practical reference value. This article analyzes the current status and existing problems of nursing management, and puts forward some problems existing in the current nursing management staff's own quality, nursing quality system standards, and nursing management system. The experimental results in this article show that there are 42 cases of poor nursing due to lack of basic medical knowledge, accounting for 52%; there are 12 cases of poor nursing due to their own diseases, accounting for 15%; there were 7 cases of poor nursing due to lack of communication, accounting for 9%; there were 15 cases of poor nursing caused by unreasonable use of restraint devices, accounting for 19%. From these data, it can be seen that patients need to have basic medical knowledge and act in strict accordance with doctors' orders. Family members also need to accompany the patients more and cooperate with all parties in order to maximize the effectiveness of care.

VPS9D1-AS1, a novel long-non-coding RNA, acts as a tumor promoter by regulating the miR-324-5p/ITGA2 axis in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is among the most common malignancies worldwide. Elucidating the function and mechanism of action of the lncRNA VPS9D1-AS1 in COAD will be of great value for identifying potential therapeutic targets. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to measure the expression levels of lncRNA VPS9D1-AS1 in COAD tissues and cell lines. After knocking down the expression of VPS9D1-AS1 in two COAD cell lines, namely SW1116 and LoVo, their proliferation rate was measured by the 5-ethynyl-2'-deoxyuridine (Edu) incorporation and cell counting kit-8 (CCK-8) viability assays, migration and invasion abilities were assessed by wound healing and Transwell assays, and apoptosis rate was measured withflow cytometry. Additionally, the dual luciferase reporter assay system was used to investigate the targeting of miR-324-5p to VPS9D1-AS1 and ITGA2 3'-UTR. The inhibitory effects of the miR-324-5p/ITGA2 axis on the function of VPS9D1-AS1 were also examined. In vivo tumorigenesis assay was performed in nude mice injected with VPS9D1-AS1 shRNA or control shRNA lentivirus-transfected LoVo cells. RESULTS: VPS9D1-AS1 was found to be upregulated in COAD tissues and cell lines. VPS9D1-AS1 knockdown inhibited the COAD cell proliferation, migration and invasion and increased the apoptosis rate. In addition, we have demonstrated that miR-324-5p targets VPS9D1-AS1 and ITGA2 3'-UTR, and miR-324-5p silencing or forced ITGA2 expression attenuated the effect of VPS9D1-AS1 knockdown. CONCLUSION: This study identified a novel competing endogenous RNA (ceRNA) pathway that potentially associates with the oncogenic functions of VPS9D1-AS1, miR-324-5p, and ITGA2 in COAD, which could contribute to the identification of new therapeutic approaches targeting COAD.

Association between parity and bone mineral density in postmenopausal women.

BACKGROUND: Pregnancy has been considered a risk factor for the development of osteoporosis. Despite much research in this field, the relationship between parity and bone mineral density (BMD) is still controversial. Therefore, we conducted this study to investigate whether there was an association between parity and BMD of the femoral neck and lumbar spine in postmenopausal women. METHODS: Cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES). Three linear regression models, Model 1 (unadjusted), Model 2 (adjusted for age and body mass index (BMI)), and Model 3 (adjusted for all covariates), were established to evaluate the relationship between parity and BMD. In addition, the p value trend of BMD in the different parity groups was mutually verified with the results of multiple regression. Multiple logistic regression models were used to assess the relationship between parity and osteoporosis. RESULTS: In total, 924 postmenopausal women aged 45-65 years were eligible for this study. After adjustment for potential confounders, women with ≥ 6 parities had significantly lower lumbar spine BMD than women with 1-2 parities (ß = - 0.072, 95% CI: - 0.125, - 0.018, P = 0.009). However, there was no correlation between parity and femoral neck BMD in any of the three regression models. Furthermore, ≥ 6 parities were associated with a significantly higher prevalence of lumbar spine osteoporosis compared with 1-2 parities (OR = 3.876, 95% CI: 1.637, 9.175, P = 0.002). CONCLUSIONS: After adjustment for BMD-related risk factors, ≥ 6 parities were associated with decreased lumbar spine BMD but not femoral neck BMD in postmenopausal women. This suggests that postmenopausal women with high parity are at increased risk of lumbar osteoporotic fractures and should pay more attention to their bone health.

Comparison of clinical and imaging features between pulmonary tuberculosis complicated with lung cancer and simple pulmonary tuberculosis: a systematic review and meta-analysis.

This review aimed to compare the clinical features and CT imaging features between patients with pulmonary tuberculosis (PTB) and lung cancer and patients with PTB alone. That would help to analyse the differences between the two and consequently providing a theoretical basis for the clinical diagnosis and treatment for the patients. Relevant case-control studies focusing on the clinical and CT imaging characteristics between PTB with lung cancer and PTB alone were systematically searched from five electronic databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for comparison. As of 2021-07-06, a total of 1735 articles were retrieved. But only 15 articles were finally included for meta-analysis. The results showed a higher proportion of irritable cough, haemorrhagic pleural effusion and lower proportion of night sweating in PTB patients with lung cancer than in PTB patients, and the differences were statistically significant (irritable cough: OR 2.43, 95% CI 1.43-4.11; haemorrhagic pleural effusion: OR 5.73, 95% CI 1.63-20.12; night sweating: OR 0.56, 95% CI 0.36-0.87). In addition, there are many differences in the imaging characteristics of the two types of patients. In conclusion, this review summarises the similarities and differences in clinical symptoms and imaging features between patients with PTB and lung cancer and patients with PTB alone, suggesting that we should be alert to the occurrence of lung cancer in patients with obsolete PTB relapse.

Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice.

Although circadian rhythms are thought to be essential for maintaining body health, the effects of chronic circadian disruption during neurodevelopment remain elusive. Here, using the "Short Day" (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was applied from embryonic day 1 to postnatal day 42, we investigated the molecular and behavioral changes after circadian disruption in mice. Adult SD mice fully entrained to the 8 h/8 h LD cycle, and the circadian oscillations of the clock proteins, PERIOD1 and PERIOD2, were disrupted in the suprachiasmatic nucleus and the hippocampus of these mice. By RNA-seq widespread changes were identified in the hippocampal transcriptome, which are functionally associated with neurodevelopment, translational control, and autism. By western blotting and immunostaining hyperactivation of the mTOR and MAPK signaling pathways and enhanced global protein synthesis were found in the hippocampi of SD mice. Electrophysiological recording uncovered enhanced excitatory, but attenuated inhibitory, synaptic transmission in the hippocampal CA1 pyramidal neurons. These functional changes at synapses were corroborated by the immature morphology of the dendritic spines in these neurons. Lastly, autistic-like animal behavioral changes, including impaired social interaction and communication, increased repetitive behaviors, and impaired novel object recognition and location memory, were found in SD mice. Together, these results demonstrate molecular, cellular, and behavioral changes in SD mice, all of which resemble autistic-like phenotypes caused by circadian rhythm disruption. The findings highlight a critical role for circadian rhythms in neurodevelopment.

miR-23b-3p Inhibits the Oncogenicity of Colon Adenocarcinoma by Directly Targeting NFE2L3.

BACKGROUND AND AIMS: MicroR-23b-3p (miR-23b-3p) has been found to be abnormally expressed in a variety of malignant tumors and to play a role in tumor inhibition or promotion. However, the regulatory mechanism of miR-23b-3p in COAD remains unclear. The purpose of this study was to investigate the clinical significance of miR-23b-3p expression in COAD cells and to explore its role and regulatory mechanism in the growth of COAD. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure miR-23b-3p expression in COAD tissues and cell lines. After transfecting miR-23b-3p mimics into two human COAD cell lines (SW620 and LoVo), the cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation, the Transwell assay was used to measure cell migration and invasion capacity, and flow cytometry was used to evaluate cell apoptosis in vitro. In addition, a luciferase reporter assay was used to determine whether miR-23b-3p targets NFE2L3. The downstream regulatory mechanisms of miR-23b-3p action in COAD cells were also investigated. For in vivo tumorigenesis assay, COAD cells stably overexpressing miR-23b-3p were injected subcutaneously into the flank of nude mice to obtain tumors. RESULTS: Significantly decreased expression of miR-23b-3p was detected in COAD tissues and cell lines. Exogenous miR-23b-3p expression inhibited cell proliferation, migration, and invasion and promoted cell apoptosis of COAD cells in vitro. Nuclear factor erythroid 2 like 3 (NFE2L3) was identified as a direct target gene of miR-23b-3p. In addition, reintroduction of NFE2L3 partially abolished the anticancer effects of miR-23b-3p on COAD cells. Furthermore, miR-23b-3p overexpression hindered the growth of COAD cells in vivo. CONCLUSION: miR-23b-3p inhibited the oncogenicity of COAD cells in vitro and in vivo by directly targeting NFE2L3, suggesting the importance of the miR-23b-3p/NFE2L3 pathway in the development of COAD.

Interleukin-33 and its receptor soluble suppression of tumorigenicity 2 in the diagnosis of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common pregnancy-related disease that increases the risk of metabolic disorders for the pregnancies and their offspring. GDM could be effectively prevented by early diagnosis and timely treatment. METHODS: 120 patients with GDM and 108 gestational week-matched pregnancies with normal glucose tolerance (NGT) were enrolled in our study. Their blood samples were collected, and demographic characteristics were analysed. RESULTS: Compared to NGT pregnancies, patients with GDM had increased the secretions of interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), IL-6 and tumour necrosis factor-α (TNF-α) in their plasma with elevated homeostatic model assessment (HOMA). Moreover, IL-33/sST2 was positively correlated with HOMA, IL-6 and TNF-α levels in the plasma of patients with GDM respectively. CONCLUSION: IL-33/sST2 might serve as a novel potential biomarker for early diagnosis of GDM.

Developmental plasticity of NMDA receptors at the calyx of Held synapse.

Excitatory synaptic transmission is largely mediated by glutamate receptors in central synapses, such as the calyx of Held synapse in the auditory brainstem. This synapse is best known for undergoing extensive morphological and functional changes throughout early development and thereby has served as a prominent model system to study presynaptic mechanisms of neurotransmitter release. However, the pivotal roles of N-methyl-d-aspartate receptors (NMDARs) in gating acute forms of activity-dependent, persistent plasticity in vitro and chronic developmental remodeling in vivo are hardly noted. This article will provide a retrospective review of key experimental evidence to conceptualize the impact of a transient abundance of NMDARs during the early postnatal stage on the functionality of fast-spiking central synapses while raising a series of outstanding questions that are of general significance for understanding the developing brain in health and diseases. This article is part of the special Issue on "Glutamate Receptors - NMDA receptors".