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AIMS AND OBJECTIVES: To identify and synthesise nurses' experiences of competence in lifestyle counselling with adult patients in healthcare settings. BACKGROUND: Modifiable lifestyle risk behaviours contribute to an increased prevalence of chronic diseases worldwide. Lifestyle counselling is part of nurses' role which enables them to make a significant contribution to patients' long-term health in various healthcare contexts, but requires particular competence. DESIGN: Qualitative systematic literature review and meta-aggregation. METHOD: The review was guided by Joanna Briggs Institute's methodology for conducting synthesis of qualitative studies. PRISMA-checklist guided the review process. Relevant original studies were search from databases (CINAHL, PubMed, Scopus, Medic and Psych Articles, Ebscho Open Dissertations and Web of Science). After researcher consensus was reached and quality of the studies evaluated, 20 studies were subjected to meta-aggregation. RESULTS: From 20 studies meeting the inclusion criteria, 75 findings were extracted and categorised into 13 groups based on their meaning, resulting in the identification of 5 synthesised findings for competence description: Supporting healthy lifestyle adherence, creating interactive and patient-centred counselling situations, acquiring competence through clinical experience and continuous self-improvement, collaborating with other professionals and patients, planning lifestyle counselling and managing work across various stages of the patient's disease care path. CONCLUSION: The review provides an evidence base that can be used to support nurses' competence in lifestyle counselling when working with adult patients in healthcare settings. Lifestyle counselling competence is a complex and rather abstract phenomenon. The review identified, analysed and synthesised the evidence derived from nurses' experience which shows that lifestyle counselling competence is a multidimensional entity which relates to many other competencies within nurses' work. IMPLICATIONS FOR THE PROFESSION: Recognising the competencies of nurses in lifestyle counselling for adult patients can stimulate nurses' motivation. The acquisition of these competencies can have a positive impact on patients' lives and their health. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. IMPACT: The research may enhance nurses' competence in lifestyle counselling, leading to improved health outcomes, better adherence to recommendations and overall well-being. It may also drive the development of interventions, improving healthcare delivery in lifestyle counselling. REPORTING METHOD: The review was undertaken and reported using the PRISMA guidelines. PROTOCOL REGISTRATION: Blinded for the review.
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Competencia Clínica , Consejo , Investigación Cualitativa , Adulto , Humanos , Consejo/métodos , Estilo de Vida , Rol de la Enfermera/psicologíaRESUMEN
Neuroinflammation is a salient part of diverse neurological and psychiatric pathologies that associate with neuronal hyperexcitability, but the underlying molecular and cellular mechanisms remain to be identified. Here, we show that peripheral injection of lipopolysaccharide (LPS) renders the dentate gyrus (DG) hyperexcitable to perforant pathway stimulation in vivo and increases the internal spiking propensity of dentate granule cells (DGCs) in vitro 24 h post-injection (hpi). In parallel, LPS leads to a prominent downregulation of chloride extrusion via KCC2 and to the emergence of NKCC1-mediated chloride uptake in DGCs under experimental conditions optimized to detect specific changes in transporter efficacy. These data show that acute neuroinflammation leads to disruption of neuronal chloride regulation, which unequivocally results in a loss of GABAergic inhibition in the DGCs, collapsing the gating function of the DG. The present work provides a mechanistic explanation for neuroinflammation-driven hyperexcitability and consequent cognitive disturbance.
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Cloruros , Lipopolisacáridos , Humanos , Cloruros/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Enfermedades Neuroinflamatorias , Giro Dentado/metabolismo , Neuronas/metabolismoRESUMEN
PURPOSE: To review and synthesize the available evidence on the effectiveness of preparatory digital counseling for children undergoing diagnostic imaging and their parents in terms of patient-related and imaging outcomes. METHODS: Relevant studies were identified by searching databases and gray literature resources. References from full-text articles identified in the initial search were searched manually to identify additional relevant studies. The reviewed literature included studies on children and adolescents aged 3 to 21 years, their parents, or both, who participated in digital counseling interventions before medical imaging examinations. Literature selection and quality appraisal were conducted by 2 independent reviewers. Data were extracted using standardized tools and synthesized using the narrative synthesis approach. This review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Five randomized controlled trials and quasi-experimental studies were included in this review. Digital counseling was provided via multiple approaches with interactive elements. Digital counseling was reported to be effective at reducing anxiety and increasing knowledge and satisfaction among children and their parents. It also appeared to reduce the need for general anesthesia and to improve the success of imaging procedures based on image quality and number of repeated images required. Digital counseling also appeared to increase children's confidence and help them remain still during the imaging process. DISCUSSION: The increased knowledge from digital counseling can strengthen senses of security and self-efficacy, which are important for successful medical imaging examinations, especially in children. The digital counseling applications used in the included studies are location-independent, and children and their parents can use them as often as they want, which might help ensure the provision of sufficient counseling before procedures. CONCLUSIONS: Digital counseling seems to be an effective method for preparing children for diagnostic imaging and a useful tool for facilitating successful medical imaging examinations of children. Because of the small number of original studies in this area, further research is needed to confirm the effectiveness of digital counseling in children's diagnostic imaging.
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Ansiedad , Consejo , Adolescente , Niño , Humanos , Diagnóstico por ImagenRESUMEN
INTRODUCTION: This study investigated whether a 360° virtual counselling environment (360°VCE) was more effective at decreasing patients' anxiety than routine standard of care counselling for patients undergoing coronary computed tomography angiography (CCTA), and if there was any difference in the process times for both of these groups. METHODS: A total of 86 patients underwent CCTA in this randomised controlled trial. Patients were randomly assigned to intervention and control groups. The 360°VCE was developed using spherical panoramic images and non-immersive 360° technology. The primary outcome, anxiety, was measured using the State-Trait Anxiety Inventory (STAI). The secondary outcome, CCTA process time, was measured from the time of arrival in the department until end of examination. RESULTS: Pre-scan anxiety was lower among patients in the 360°VCE group immediately before CCTA in comparison to patients in the control group (p = 0.015). Women demonstrated higher levels of anxiety than men in both groups. No between-group differences were discerned in CCTA process time. CONCLUSION: Access to 360°VCE can reduce patients' pre-CCTA anxiety levels. IMPLICATIONS FOR PRACTICE: The presented results can be used to improve patient counselling and care, reduce anxiety among patients undergoing CCTA, and optimise the CCTA examination procedure.
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Ansiedad , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Consejo , Terapia de Exposición Mediante Realidad Virtual , Ansiedad/diagnóstico , Ansiedad/prevención & control , Angiografía por Tomografía Computarizada/psicología , Factores de Tiempo , Terapia de Exposición Mediante Realidad Virtual/normas , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Factores Sexuales , Resultado del Tratamiento , Angiografía Coronaria/psicología , Consejo/métodos , Consejo/normasRESUMEN
The Na-K-2Cl cotransporter NKCC1 is widely expressed in cells within and outside the brain. However, our understanding of its roles in brain functions throughout development, as well as in neuropsychiatric and neurological disorders, has been severely hindered by the lack of reliable data on its developmental and (sub)cellular expression patterns. We provide here the first properly controlled analysis of NKCC1 protein expression in various cell types of the mouse brain using custom-made antibodies and an NKCC1 knock-out validated immunohistochemical procedure, with parallel data based on advanced mRNA approaches. NKCC1 protein and mRNA are expressed at remarkably high levels in oligodendrocytes. In immature neurons, NKCC1 protein was located in the somata, whereas in adult neurons, only NKCC1 mRNA could be clearly detected. NKCC1 immunoreactivity is also seen in microglia, astrocytes, developing pericytes, and in progenitor cells of the dentate gyrus. Finally, a differential expression of NKCC1 splice variants was observed, with NKCC1a predominating in non-neuronal cells and NKCC1b in neurons. Taken together, our data provide a cellular basis for understanding NKCC1 functions in the brain and enable the identification of major limitations and promises in the development of neuron-targeting NKCC1-blockers.
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Encéfalo , Neuronas , Ratones , Animales , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Encéfalo/metabolismo , Neuronas/metabolismo , ARN Mensajero/metabolismo , Hipocampo/metabolismoRESUMEN
BACKGROUND: Patients who are chronically ill need novel patient counseling methods to support their self-care at different stages of the disease. At present, knowledge of how effective digital counseling is at managing patients' anxiety, depression, and adherence to treatment seems to be fragmented, and the development of digital counseling will require a more comprehensive view of this subset of interventions. OBJECTIVE: This study aims to identify and synthesize the best available evidence on the effectiveness of digital counseling environments at improving anxiety, depression, and adherence to treatment among patients who are chronically ill. METHODS: Systematic searches of the EBSCO (CINAHL), PubMed, Scopus, and Web of Science databases were conducted in May 2019 and complemented in October 2020. The review considered studies that included adult patients aged ≥18 years with chronic diseases; interventions evaluating digital (mobile, web-based, and ubiquitous) counseling interventions; and anxiety, depression, and adherence to treatment, including clinical indicators related to adherence to treatment, as outcomes. Methodological quality was assessed using the standardized Joanna Briggs Institute critical appraisal tool for randomized controlled trials or quasi-experimental studies. As a meta-analysis could not be conducted because of considerable heterogeneity in the reported outcomes, narrative synthesis was used to synthesize the results. RESULTS: Of the 2056 records screened, 20 (0.97%) randomized controlled trials, 4 (0.19%) pilot randomized controlled trials, and 2 (0.09%) quasi-experimental studies were included. Among the 26 included studies, 10 (38%) digital, web-based interventions yielded significantly positive effects on anxiety, depression, adherence to treatment, and the clinical indicators related to adherence to treatment, and another 18 (69%) studies reported positive, albeit statistically nonsignificant, changes among patients who were chronically ill. The results indicate that an effective digital counseling environment comprises high-quality educational materials that are enriched with multimedia elements and activities that engage the participant in self-care. Because of the methodological heterogeneity of the included studies, it is impossible to determine which type of digital intervention is the most effective for managing anxiety, depression, and adherence to treatment. CONCLUSIONS: This study provides compelling evidence that digital, web-based counseling environments for patients who are chronically ill are more effective than, or at least comparable to, standard counseling methods; this suggests that digital environments could complement standard counseling.
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Trastornos de Ansiedad , Depresión , Adolescente , Adulto , Ansiedad/terapia , Enfermedad Crónica , Consejo , Depresión/terapia , HumanosRESUMEN
Intracellular pH is a potent modulator of neuronal functions. By catalyzing (de)hydration of CO2 , intracellular carbonic anhydrase (CAi ) isoforms CA2 and CA7 contribute to neuronal pH buffering and dynamics. The presence of two highly active isoforms in neurons suggests that they may serve isozyme-specific functions unrelated to CO2 -(de)hydration. Here, we show that CA7, unlike CA2, binds to filamentous actin, and its overexpression induces formation of thick actin bundles and membrane protrusions in fibroblasts. In CA7-overexpressing neurons, CA7 is enriched in dendritic spines, which leads to aberrant spine morphology. We identified amino acids unique to CA7 that are required for direct actin interactions, promoting actin filament bundling and spine targeting. Disruption of CA7 expression in neocortical neurons leads to higher spine density due to increased proportion of small spines. Thus, our work demonstrates highly distinct subcellular expression patterns of CA7 and CA2, and a novel, structural role of CA7.
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Actinas , Anhidrasas Carbónicas , Citoesqueleto de Actina/metabolismo , Actinas/genética , Actinas/metabolismo , Anhidrasas Carbónicas/genética , Espinas Dendríticas/metabolismo , Hipocampo/metabolismo , Neuronas/metabolismoRESUMEN
KCC2, best known as the neuron-specific chloride-extruder that sets the strength and polarity of GABAergic currents during neuronal maturation, is a multifunctional molecule that can regulate cytoskeletal dynamics via its C-terminal domain (CTD). We describe the molecular and cellular mechanisms involved in the multiple functions of KCC2 and its splice variants, ranging from developmental apoptosis and the control of early network events to the formation and plasticity of cortical dendritic spines. The versatility of KCC2 actions at the cellular and subcellular levels is also evident in mature neurons during plasticity, disease, and aging. Thus, KCC2 has emerged as one of the most important molecules that shape the overall neuronal phenotype.
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Simportadores , Cloruros/metabolismo , Humanos , Neuronas/metabolismoRESUMEN
Ionotropic GABA transmission is mediated by anion (mainly Cl-)-permeable GABAA receptors (GABAARs). In immature neurons, GABA exerts depolarizing and sometimes functionally excitatory actions, based on active uptake of Cl- by the Na-K-2Cl cotransporter NKCC1. While functional evidence firmly shows NKCC1-mediated ion transport in immature and diseased neurons, molecular detection of NKCC1 in the brain has turned out to be extremely difficult. In this review, we describe the highly inconsistent data that are available on the cell type-specific expression patterns of the NKCC1 mRNA and protein in the CNS. We discuss the major technical caveats, including a lack of knock-out-controlled immunohistochemistry in the forebrain, possible effects of alternative splicing on the binding of antibodies and RNA probes, and the wide expression of NKCC1 in different cell types, which make whole-tissue analyses of NKCC1 useless for studying its neuronal expression. We also review novel single-cell RNAseq data showing that most of the NKCC1 in the adult CNS may, in fact, be expressed in non-neuronal cells, especially in glia. As future directions, we suggest single-cell NKCC1 mRNA and protein analyses and the use of genetically tagged endogenous proteins or systematically designed novel antibodies, together with proper knock-out controls, for the visualization of endogenous NKCC1 in distinct brain cell types and their subcellular compartments.
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Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Empalme Alternativo , Animales , Sistema Nervioso Central/metabolismo , Cloruros/metabolismo , Epilepsia/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Inmunohistoquímica , Transporte Iónico , Ratones , Neuroglía/metabolismo , Neuronas/metabolismo , Prosencéfalo , ARN Mensajero/metabolismo , RNA-Seq , Ratas , Receptores de GABA-A/metabolismo , Simportadores/metabolismo , Ácido gamma-AminobutíricoRESUMEN
OBJECTIVES: The aim of this systematic review was to evaluate the effectiveness of educational interventions in digital collaborative learning implemented in nursing education. DESIGN: A systematic literature review of randomised controlled trials (RCTs) was carried out in accordance with Joanna Briggs Institute (JBI) and Centre for Reviews and Dissemination guidelines and the PRISMA statement. DATA SOURCES: CINAHL (EBSCO), ERIC, MEDLINE (Ovid) and Scopus databases were used to identify original peer-reviewed RCT studies published between 2003 and 2018. REVIEW METHOD: The 'hits' were systematically screened by title, abstract and full text by two authors acting independently. The quality of the selected original studies was evaluated using the quality assessment criteria of the JBI and Cochrane collaboration's tool for assessing risk of bias in randomised trials. The studies were analysed by narrative synthesis. RESULTS: Five peer-reviewed RCT studies were included in the review. All participants in these studies (647 in total) were nursing students exposed to educational interventions in various nursing programme courses. The reviewed studies indicated that digital collaborative learning increased students' knowledge and nursing skills. The results show that collaborative learning in digital learning environments enhanced nursing students' interaction and collaborative skills, problem-solving skills, satisfaction and motivation for learning. CONCLUSION: Collaborative learning in digital learning environments has encouraging effects in enhancing nursing students' knowledge, competence, satisfaction and problem-solving skills. Moreover, evidence-based digital collaborative learning is becoming increasingly effective in nursing education, as available tools and teachers' abilities to use them are improving and providing new learning activities to boost students' learning outcomes in higher education. Thus, its systematic use in digital collaborative learning environments in various nursing courses is recommended.
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Conducta Cooperativa , Educación en Enfermería/organización & administración , Aprendizaje , Humanos , Evaluación de Programas y Proyectos de Salud , Estudiantes de EnfermeríaRESUMEN
Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.
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Regulación del Desarrollo de la Expresión Génica/fisiología , Inhibición Neural/fisiología , Corteza Prefrontal/citología , Células Piramidales/fisiología , Sinapsis/fisiología , Factores de Edad , Animales , Animales Recién Nacidos , Proteínas Portadoras/metabolismo , Dendritas/metabolismo , Espinas Dendríticas/fisiología , Embrión de Mamíferos , Técnicas In Vitro , Isoquinolinas/metabolismo , Proteínas de la Membrana/metabolismo , Microscopía Confocal , Neurogénesis/fisiología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/crecimiento & desarrollo , Ratas , Ratas Wistar , Factores de Tiempo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABAA receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth.
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Encéfalo/embriología , Interneuronas/fisiología , Vasopresinas/fisiología , Animales , Encéfalo/crecimiento & desarrollo , Potenciales Evocados , Femenino , Cobayas , Hipocampo/embriología , Hipocampo/crecimiento & desarrollo , Hipocampo/fisiología , Masculino , Red Nerviosa/fisiología , Parto , Ratas , Ratas Wistar , Ácido gamma-Aminobutírico/metabolismoRESUMEN
BACKGROUND: Human epidemiological data suggest a link between anesthesia exposure in early postnatal life and subsequent lasting neurocognitive alterations. Understanding the underlying mechanisms of this potential association is of paramount importance in an attempt to develop protective strategies. While general anesthetics are powerful modulators of GABAergic neurotransmission, little is known about the impact of these drugs on developing GABAergic networks. Here we addressed this issue by evaluating the impact of a 6-h-long midazolam exposure on the development of calbindin-, calretinin- and parvalbumin-expressing GABAergic interneurons. METHODS: Physiological expression patterns of calbindin-, calretinin-, and parvalbumin-positive neurons as well as the impact of a 6-h-long midazolam exposure on these cell populations were evaluated in the medial prefrontal cortex of Wistar rats at defined stages of the brain growth spurt using stereological analysis. Activated caspase-3 immunohistochemistry was used to quantify apoptotic death in controls and midazolam-treated subjects. RESULTS: In control animals, the number of parvalbumin expressing cells significantly (p<0.01) increased while those of calbindin positive populations significantly (p<0.01) decreased between postnatal day 10 and 20. Expression of calretinin remained constant during this period. Immediately following exposure, midazolam induced neuroapoptosis at both early (postnatal day 5, p=0.016) and later (postnatal day 15, p=0.025) stages of brain development. While this did not diminish overall neuronal density in the medial prefrontal cortex, exposure at P5 led to a subsequent increase in the number of parvalbumin positive neurons in lower cortical layers, and midazolam administration at P15 increased the number of both parvalbumin and calretinin expressing neurons 5 days following exposure. CONCLUSION: These observations demonstrate that midazolam exposure can impair the physiological differentiation patterns of GABAergic interneurons during the brain growth spurt. Considering the important role of GABAergic networks in neuronal physiology, these data provide us with one potential mechanism that could account for the lasting neurobehavioral and cognitive deficits observed in the context of anesthesia exposure in the early postnatal period.
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Calbindina 2/metabolismo , Calbindinas/metabolismo , Midazolam/administración & dosificación , Parvalbúminas/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiología , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/fisiología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Hipnóticos y Sedantes/administración & dosificación , Ratas , Ratas WistarRESUMEN
In adult rodent olfactory bulb, GABAergic signaling regulates migration, differentiation, and synaptic integration of newborn granule cells (GCs), migrating from the subventricular zone. Here we show that these effects depend on the formation of a postsynaptic scaffold organized by gephyrin-the main scaffolding protein of GABAergic synapses, which anchors receptors and signaling molecules to the postsynaptic density-and are regulated by the phosphorylation status of gephyrin. Using lentiviral vectors to selectively transfect adult-born GCs, we observed that overexpression of the phospho-deficient gephyrin mutant eGFP-gephyrin(S270A), which facilitates the formation of supernumerary GABAergic synapses in vitro, favors dendritic branching and the formation of transient GABAergic synapses on spines, identified by the presence of α2-GABAA Rs. In contrast, overexpression of the dominant-negative eGFP-gephyrin(L2B) (a chimera that is enzymatically active but clustering defective), curtailed dendritic growth, spine formation, and long-term survival of GCs, pointing to the essential role of gephyrin cluster formation for its function. We could exclude any gephyrin overexpression artifacts, as GCs infected with eGFP-gephyrin were comparable to those infected with eGFP alone. The opposite effects induced by the two gephyrin mutant constructs indicate that the gephyrin scaffold at GABAergic synapses orchestrates signaling cascades acting on the cytoskeleton to regulate neuronal growth and synapse formation. Specifically, gephyrin phosphorylation emerges as a novel mechanism regulating morphological differentiation and long-term survival of adult-born olfactory bulb neurons.
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Proteínas Portadoras/metabolismo , Proteínas de la Membrana/metabolismo , Neurogénesis/fisiología , Neuronas/citología , Neuronas/metabolismo , Bulbo Olfatorio/citología , Densidad Postsináptica/metabolismo , Factores de Edad , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/ultraestructura , Movimiento Celular/genética , Supervivencia Celular/genética , Dendritas/metabolismo , Dendritas/ultraestructura , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/ultraestructura , Ratones , Mutación/genética , Densidad Postsináptica/ultraestructura , Receptores de GABA-A/metabolismo , Transducción Genética , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismoRESUMEN
The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.
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Astrocitos/fisiología , Hipocampo/citología , Neuronas/citología , Familia de Aldehído Deshidrogenasa 1 , Animales , Astrocitos/ultraestructura , Bromodesoxiuridina/metabolismo , Espinas Dendríticas/efectos de los fármacos , Espinas Dendríticas/metabolismo , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/genética , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Ácido Kaínico/análogos & derivados , Ácido Kaínico/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Confocal , Microscopía Inmunoelectrónica , Neurogénesis/efectos de los fármacos , Neurogénesis/genética , Neuronas/efectos de los fármacos , Técnicas de Placa-Clamp , Fosfopiruvato Hidratasa/metabolismo , Retinal-Deshidrogenasa/genética , Retinal-Deshidrogenasa/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100/metabolismo , Sinapsis/fisiología , Sinapsis/ultraestructura , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/genéticaRESUMEN
Although functional glycinergic synapses have not been identified in the hippocampus, neurons in this area express Cl(-) permeable extrasynaptic glycine receptors (GlyRs). In experiments on CA3 pyramidal neurons on postnatal day 0-6 rat hippocampal slices, we detected robust GlyR activity as a tonic current and as single-channel events. Glycine release was independent of neuronal activity or extracellular Ca(2+). The endogenous GlyR activity was strongly enhanced by inhibition of the glycine-transporter-1 (GlyT1). Blockade of GlyT1 also caused a profound increase in the baseline current induced by exogenous glycine. Inhibition of GlyT1 reduced the frequency of spontaneous network events known as field giant depolarizing potentials (fGDPs) and of the unit activity in the absence of synaptic transmission. This inhibitory action on fGDPs was mimicked by applying 2 µm glycine or 0.1 µm isoguvacine, a GABAA-receptor agonist. Furthermore, 2 µm glycine suppressed unit spiking in the absence of synaptic transmission. Hence, despite the well known depolarizing Cl(-) equilibrium potential of neonatal hippocampal neurons, physiologically relevant extracellular glycine concentrations can exert an inhibitory action. The present data show that, akin to GABA uptake, GlyT1 exerts a powerful modulatory action on network events in the newborn hippocampus.