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.

Functional Convergence of Motor and Social Processes in Lobule IV/V of the Mouse Cerebellum.

Topographic organization of the cerebellum is largely segregated into the anterior and posterior lobes that represent its "motor" and "non-motor" functions, respectively. Although patients with damage to the anterior cerebellum often exhibit motor deficits, it remains unclear whether and how such an injury affects cognitive and social behaviors. To address this, we perturbed the activity of major anterior lobule IV/V in mice by either neurotoxic lesion or chemogenetic excitation of Purkinje cells in the cerebellar cortex. We found that both of the manipulations impaired motor coordination, but not general locomotion or anxiety-related behavior. The lesioned animals showed memory deficits in object recognition and social-associative recognition tests, which were confounded by a lack of exploration. Chemogenetic excitation of Purkinje cells disrupted the animals' social approach in a less-preferred context and social memory, without affecting their overall exploration and object-based memory. In a free social interaction test, the two groups exhibited less interaction with a stranger conspecific. Subsequent c-Fos imaging indicated that decreased neuronal activities in the medial prefrontal cortex, hippocampal dentate gyrus, parahippocampal cortices, and basolateral amygdala, as well as disorganized modular structures of the brain networks might underlie the reduced social interaction. These findings suggest that the anterior cerebellum plays an intricate role in processing motor, cognitive, and social functions.

Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain.

Principal neurons encode information by varying their firing rate and patterns precisely fine-tuned through GABAergic interneurons. Dysregulation of inhibition can lead to neuropsychiatric disorders, yet little is known about the molecular basis underlying inhibitory control. Here, we find that excessive GABA release from basket cells (BCs) attenuates the firing frequency of Purkinje neurons (PNs) in the cerebellum of Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mice, a model of Fragile X Syndrome (FXS) with abrogated expression of the Fragile X Mental Retardation Protein (FMRP). This over-inhibition originates from increased excitability and Ca2+ transients in the presynaptic terminals, where Kv1.2 potassium channels are downregulated. By paired patch-clamp recordings, we further demonstrate that acutely introducing an N-terminal fragment of FMRP into BCs normalizes GABA release in the Fmr1-KO synapses. Conversely, direct injection of an inhibitory FMRP antibody into BCs, or membrane depolarization of BCs, enhances GABA release in the wild type synapses, leading to abnormal inhibitory transmission comparable to the Fmr1-KO neurons. We discover that the N-terminus of FMRP directly binds to a phosphorylated serine motif on the C-terminus of Kv1.2; and that loss of this interaction in BCs exaggerates GABA release, compromising the firing activity of PNs and thus the output from the cerebellar circuitry. An allosteric Kv1.2 agonist, docosahexaenoic acid, rectifies the dysregulated inhibition in vitro as well as acoustic startle reflex and social interaction in vivo of the Fmr1-KO mice. Our results unravel a novel molecular locus for targeted intervention of FXS and perhaps autism.

[Research Status of Application of Gold Nanoparticles in Medical Biotechnology].

In recent years, gold nanoparticles (GNPs) have attracted more and more attention for their unique physical, chemical and biological properties, and are emerging as optical probes and biocompatibility materials for use. With the application of nanogold labeling technology in the medical field, detection techniques using GNPs as immune markers will become a major labeling technique, and will have wide applications in basic and clinical medicine. In this article, recent research progress on the applications of GNPs in the detection of pathogens, nucleic acids, and proteins and in the preparation of biosensors is reviewed.

[Preliminary survey on the host of Angiostrongylus cantonensis in three plateau lakes of Yunnan Province].

OBJECTIVE: To investigated the intermediate hosts of Angiostrongylus cantonensis in three plateau lakes of Yunnan Province, and analyze the effect of temperature on A. cantonensis during 1991-2010. METHODS: An epidemiological investigation of angiostrongyliasis cantonensis in Erhai Lake, Fuxian Lake and Xingyun Lake was conducted from April to September in 2012. Snails were examined for the third stage larvae by enzyme digestion or lung examination. Rodents were captured in the fields, and their hearts and lungs were dissected for adult worms. The potential distribution of A. cantonensis and its main intermediate host Pomacea canaliculata were predicted based on degree-day models using GIS technique. RESULTS: A total of 4 950 snails were collected, belonging to 4 species, P. canaliculata, Cipangopaludina chinensis, Bellamya aeruginosa, and B. quadrata. 174 rodents were captured, belonging to 5 species. No positive samples were found. The potential distribution map showed that the distribution of A. cantonensis and P. canaliculata in Yunnan would expand with the rise of temperature, and with the passage of time they could complete one generation in the region which couldn't finish one generation in one year along with time passing. CONCLUSION: A. cantonensis are not found in the hosts. The natural environment and ecological system of the three lakes match the condition of A. cantonensis transmission.

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.

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.

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.

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.

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.

[Application of PCR and PCR-derived technologies in the detection of Angiostrongylus cantonensis].

Angiostrongyliasis is a zoonotic disease and has become one of the potentially threatening food-borne parasitic infections in China. This article reviews the advances in the application of PCR and PCR-derived techniques in detection of Angiostrongylus cantonensis.

[Killing effect of garlic extract on Schistosoma japonicum cercariae and Oncomelania snails].

The killing effect of different concentrations of garlic extract solution on Schistosoma japonicum cercariae and Oncomelania snails was observed under dissecting microscope. Mice were infected by cercariae through the abdominal skin daubed by garlic solution or by deionized water as control. The results showed that the cercariae were killed in (77.33 +/- 25.01) s in average, it needed (73.00 +/- 1.73)- (299.67 +/- 18.96) s under the garlic solution concentrations of 50.00%-0.79% respectively, while the cercariae kept alive in 600 s in the control. The snails were killed in 1 d by 100% garlic solution but no death in the control in 2 d. No mouse daubed with different concentrations of garlic solution was found infected by schistosomes while 100% of the control mice got infected. It is concluded that the garlic shows satisfactory effect in killing cercariae and Oncomelania snails, and may prevent schistosome infection by daubing the skin.

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.

GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse.

Fast excitatory synaptic transmission in central synapses is mediated primarily by AMPA receptors (AMPARs), which are heteromeric assemblies of four subunits, GluA1-4. Among these subunits, rapidly gating GluA3/4 appears to be the most abundantly expressed to enable neurotransmission with submillisecond precision at fast rates in subsets of central synapses. However, neither definitive identification of the molecular substrate for native AMPARs in these neurons, nor their hypothesized functional roles in vivo has been unequivocally demonstrated, largely due to lack of specific antagonists. Using GluA3 or GluA4 knockout (KO) mice, we investigated these issues at the calyx of Held synapse, which is known as a high-fidelity synapse involved in sound localization. Patch-clamp recordings from postsynaptic neurons showed that deletion of GluA4 significantly slowed the time course of both evoked and miniature AMPAR-mediated excitatory postsynaptic currents (AMPAR-EPSCs), reduced their amplitude, and exacerbated AMPAR desensitization and short-term depression (STD). Surprisingly, presynaptic release probability was also elevated, contributing to severe STD at GluA4-KO synapses. In contrast, only marginal changes in AMPAR-EPSCs were found in GluA3-KO mice. Furthermore, independent of changes in intrinsic excitability of postsynaptic neurons, deletion of GluA4 markedly reduced synaptic drive and increased action potential failures during high-frequency activity, leading to profound deficits in specific components of the auditory brainstem responses associated with synchronized spiking in the calyx of Held synapse and other related neurons in vivo. These observations identify GluA4 as the main determinant for fast synaptic response, indispensable for driving high-fidelity neurotransmission and conveying precise temporal information.

Action potential bursts enhance transmitter release at a giant central synapse.

Patterns of action potentials (APs), often in the form of bursts, are critical for coding and processing information in the brain. However, how AP bursts modulate secretion at synapses remains elusive. Here, using the calyx of Held synapse as a model we compared synaptic release evoked by AP patterns with a different number of bursts while the total number of APs and frequency were fixed. The ratio of total release produced by multiple bursts to that by a single burst was defined as 'burst-effect'.We found that four bursts of 25 stimuli at 100 Hz increased the totalcharge of EPSCs to 1.47 ± 0.04 times that by a single burst of 100 stimuli at the same frequency.Blocking AMPA receptor desensitization and saturation did not alter the burst-effect, indicating that it was mainly determined by presynaptic mechanisms. Simultaneous dual recordings of presynaptic membrane capacitance (Cm) and EPSCs revealed a similar burst-effect, being 1.58±0.13by Cm and 1.49±0.05 by EPSCs. Reducing presynapticCa2+ influx by lowering extracellular Ca2+concentration or buffering residual intracellular Ca2+ with EGTA inhibited the burst-effect. We further developed a computational model largely recapitulating the burst-effect and demonstrated that this effect is highly sensitive to dynamic change in availability of the releasable pool of synaptic vesicles during various patterns of activities. Taken together, we conclude that AP bursts modulate synaptic output mainly through intricate interaction between depletion and replenishment of the large releasable pool. This burst-effect differs from the somatic burst-effect previously described from adrenal chromaffin cells, which substantially depends on activity-induced accumulation of Ca2+ to facilitate release of a limited number of vesicles in the releasable pool. Hence, AP bursts may play an important role in dynamically regulating synaptic strength and fidelity during intense neuronal activity at central synapses.

[Application of molecular biological techniques in Taenia identification].

The traditional identification of Taenia spp. based on morphological features of adult and cysticercus has difficulties in identifying the morphologically similar species. The recent development of molecular techniques provides more scientific ways for distinguishing Taenia species. This paper summarizes the application of molecular biological techniques in the identification of Taenia, such as analysis of DNA sequence, PCR-RFLP and LAMP.

[Application of immune colloidal gold technique on the diagnosis of parasitoses].

Immune colloidal gold (ICG) technique is a simple, rapid, accurate diagnosis method. At present, ICG technique has been widely applied in the accessory diagnosis of parasitoses, and this article reviews the latest progress of ICG technique applied in parasitology.

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".

Effects of nursing care in fast-track surgery on postoperative pain, psychological state, and patient satisfaction with nursing for glioma.

BACKGROUND: The brain is the most complex organ in the human body. Treatment for a glioma always involves a multi-disciplinary team. Nursing care in fast-track surgery or enhanced recovery after surgery is such kind of work implemented by an interdisciplinary team to provide services to patients to improve their outcomes. AIM: To explore the effects of nursing care in fast-track surgery on postoperative pain, psychological state, and patient satisfaction with nursing for glioma. METHODS: From June 2018 to June 2020, 138 patients who underwent operation for glioma at Cancer Hospital Affiliated to Chongqing University were selected. They were categorized into groups according to different nursing care that they received. Of them, 69 patients receiving nursing care in fast-track surgery were included in an experimental group, and 69 patients receiving conventional postoperative nursing were included in a control group. Visual analogue scale was used to evaluate postoperative pain in the two groups immediately after the operation and at 3 d after the operation. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the psychological status of patients immediately after operation and on the 3rd postoperative day. A self-made satisfaction scale for patient satisfaction with nursing was used to evaluate and compare patient satisfaction with nursing between the two groups. RESULTS: Time to excretion, time to out-of-bed activities, and length of hospital stay were significantly shorter in the observation group than in the control group (P < 0.05). There was no significant difference in duration of operative time or intraoperative bleeding between the two groups (P > 0.05). There was no significant difference in postoperative pain score between the two groups (P > 0.05). The pain score was significantly lower in the observation group than in the control group at 3 d after the operation (P < 0.05). There was no significant difference in postoperative SAS or SDS score between the two groups (P > 0.05). SAS and SDS scores were significantly lower in the observation group than in the control group at 3 d after operation (P < 0.05). The rate of patient satisfaction with nursing was 94.2% in the observation group, which was significantly higher than that (81.2%) of the control group (P < 0.05). CONCLUSION: Nursing care in fast-track surgery can relieve postoperative pain, anxiety, and depression, and improve patient satisfaction with nursing in patients with glioma, which is worthy of clinical application.