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OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.
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Militares , Humanos , Estudos Retrospectivos , Militares/estatística & dados numéricos , Masculino , Estudos de Coortes , Reino Unido , Seleção de Pessoal/métodos , Seleção de Pessoal/estatística & dados numéricos , Saúde Ocupacional/estatística & dados numéricos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Feminino , Índia/epidemiologia , AdultoRESUMO
Ice worlds are at the forefront of astrobiological interest because of the evidence of subsurface oceans. Enceladus in particular is unique among the icy moons because there are known vent systems that are likely connected to a subsurface ocean, through which the ocean water is ejected to space. An existing study has shown that sending small robots into the vents and directly sampling the ocean water is likely possible. To enable such a mission, NASA's Jet Propulsion Laboratory is developing a snake-like robot called Exobiology Extant Life Surveyor (EELS) that can navigate Enceladus' extreme surface and descend an erupting vent to capture unaltered liquid samples and potentially reach the ocean. However, navigating to and through Enceladus' environment is challenging: Because of the limitations of existing orbital reconnaissance, there is substantial uncertainty with respect to its geometry and the physical properties of the surface/vents; communication is limited, which requires highly autonomous robots to execute the mission with limited human supervision. Here, we provide an overview of the EELS project and its development effort to create a risk-aware autonomous robot to navigate these extreme ice terrains/environments. We describe the robot's architecture and the technical challenges to navigate and sense the icy environment safely and effectively. We focus on the challenges related to surface mobility, task and motion planning under uncertainty, and risk quantification. We provide initial results on mobility and risk-aware task and motion planning from field tests and simulated scenarios.
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BACKGROUND: Previous research has shown that, in comparison with non-pregnant women of reproductive age, pregnant women with COVID-19 are more likely to be admitted to critical care, receive invasive ventilation, and die. At present there are limited data in relation to outcomes and healthcare utilisation following hospital discharge of pregnant and recently pregnant women admitted to critical care. METHODS: A national cohort study of pregnant and recently pregnant women who were admitted to critical care in Scotland with confirmed or suspected COVID-19. We examined hospital outcomes as well as hospital re-admission rates. RESULTS: Between March 2020 and March 2022, 75 pregnant or recently pregnant women with laboratory-confirmed COVID-19 were admitted to 24 Intensive Care Units across Scotland. Almost two thirds (n=49, 65%) were from the most deprived socio-economic areas. Complete 90-day acute hospital re-admission data were available for 74 (99%) patients. Nine (12%) women required an emergency non-obstetric hospital re-admission within 90â¯days. Less than 5% of the cohort had received any form of vaccination. CONCLUSIONS: This national cohort study has demonstrated that pregnant or recently pregnant women admitted to critical care with COVID-19 were more likely to reside in areas of socio-economic deprivation, and fewer than 5% of the cohort had received any form of vaccination. More targeted public health campaigning across the socio-economic gradient is urgently required.
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COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , Masculino , Estudos de Coortes , Unidades de Terapia Intensiva , Cuidados Críticos , Escócia/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/terapiaRESUMO
INTRODUCTION: There is little research regarding patient engagement (PE) in Continuing Professional Development (CPD) programs in radiation oncology. This study aims to understand the barriers and enablers to PE in the design and implementation process of CPD programs, and advance PE in these programs moving forward. METHODS: This qualitative study involved 17 semi-structured interviews, with 5 cancer patients and 12 educators, conducted from June 2019 to April 2020. Interview data identified common themes, such as: the current state of PE in CPD programming, and key barriers and recommendations on how to engage patients in meaningful and practical ways. RESULTS: Six themes were identified related to PE: the concept of PE, ethical considerations, barriers, key considerations in planning resources, and the anticipated impact of PE on curriculum planning. CONCLUSION: Both patients and educators emphasized that creating and sustaining meaningful educator-patient relationships and giving patients an active and effective role in CPD planning would improve curriculum content. The University of Toronto Department of Radiation Oncology (UTDRO) should consider building this initiative into its strategic CPD priorities and ensure the appropriate infrastructure is in place.
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Radioterapia (Especialidade) , Currículo , Humanos , Participação do Paciente , Pesquisa QualitativaRESUMO
BACKGROUND: Radial head replacement is used to confer joint stability in the management of acute unstable elbow fractures and dislocations associated with instability. We determined the annual incidence of radial head replacement over a 22-year period in a defined population. MATERIALS AND METHODS: Hospital episode statistics were collected prospectively at a national level. This database was retrospectively examined to determine the annual incidence of radial head replacement over the study period in adults over 16 years of age. RESULTS: A total of 615 radial head replacements were performed over the 22 years studied. The overall incidence was 0.65/100,000/year (95% confidence interval, CI, 0.50-0.71). The average adult population during the period was 4,270,593. There was a steady and statistically significant increase in the incidence of radial head replacement over the study period (r 2 = 0.816; p < 0.0001). This incidence was significantly greater in women than men (odds ratio 1.46, 95% CI 1.25-1.72; p < 0.001). The peak incidence in men was 0.87/100,000 population/year in the fifth decade of life while in women the peak incidence was in the seventh decade of life (1.38/100,000 population/year). CONCLUSION: The incidence of radial head replacement has increased steadily over 22 years. We hypothesise that this represents an evolving understanding of the role of radial head replacement in acute trauma in the context of emerging literature during the study period.
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Artroplastia de Substituição/tendências , Articulação do Cotovelo/cirurgia , Fraturas do Rádio/cirurgia , Adolescente , Adulto , Distribuição por Idade , Idoso , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escócia/epidemiologia , Distribuição por Sexo , Adulto JovemRESUMO
PURPOSE: This study aimed to determine the prevalence and predictors of death or new disability following critical illness. METHODS: Prospective, multicentre cohort study conducted in six metropolitan intensive care units (ICU). Participants were adults admitted to the ICU who received more than 24 h of mechanical ventilation. The primary outcome was death or new disability at 6 months, with new disability defined by a 10% increase in the WHODAS 2.0. RESULTS: Of 628 patients with the primary outcome available (median age of 62 [49-71] years, 379 [61.0%] had a medical admission and 370 (58.9%) died or developed new disability by 6 months. Independent predictors of death or new disability included age [OR 1.02 (1.01-1.03), P = 0.001], higher severity of illness (APACHE III) [OR 1.02 (1.01-1.03), P < 0.001] and admission diagnosis. Compared to patients with a surgical admission diagnosis, patients with a cardiac arrest [OR (95% CI) 4.06 (1.89-8.68), P < 0.001], sepsis [OR (95% CI) 2.43 (1.32-4.47), P = 0.004], or trauma [OR (95% CI) 6.24 (3.07-12.71), P < 0.001] diagnosis had higher odds of death or new disability, while patients with a lung transplant [OR (95% CI) 0.21 (0.07-0.58), P = 0.003] diagnosis had lower odds. A model including these three variables had good calibration (Brier score 0.20) and acceptable discriminative power with an area under the receiver operating characteristic curve of 0.76 (95% CI 0.72-0.80). CONCLUSION: Less than half of all patients mechanically ventilated for more than 24 h were alive and free of new disability at 6 months after admission to ICU. A model including age, illness severity and admission diagnosis has acceptable discriminative ability to predict death or new disability at 6 months.
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Estado Terminal , Unidades de Terapia Intensiva , APACHE , Adulto , Idoso , Estudos de Coortes , Humanos , Lactente , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The Mars Science Laboratory (MSL) made a successful landing at Gale crater early August 2012. MSL has an environmental instrument package called the Rover Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS comprises instrumentation for the observation of atmospheric pressure, temperature of the air, ground temperature, wind speed and direction, relative humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H measurement performance and initial observations during the first 100 MSL sols as well as constraining the REMS-H results by comparing them with earlier observations and modeling results. The REMS-H device is based on polymeric capacitive humidity sensors developed by Vaisala Inc., and it makes use of transducer electronics section placed in the vicinity of the three humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The final relative humidity results appear to be convincing and are aligned with earlier indirect observations of the total atmospheric precipitable water content. The water mixing ratio in the atmospheric surface layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the precipitable water content of the atmosphere is ranging from a few to six precipitable micrometers. KEY POINTS: Atmospheric water mixing ratio at Gale crater varies from 30 to 140 ppmMSL relative humidity observation provides good dataHighest detected relative humidity reading during first MSL 100 sols is RH75.
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OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.
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Transtorno Depressivo/terapia , Adulto , Antidepressivos/uso terapêutico , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/tratamento farmacológico , Eletroconvulsoterapia/métodos , Medicina Baseada em Evidências/métodos , Humanos , Terapia Psicanalítica/métodosRESUMO
OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.
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Transtorno Bipolar/terapia , Adulto , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Eletroconvulsoterapia/métodos , Medicina Baseada em Evidências/métodos , Humanos , Compostos de Lítio/uso terapêutico , Terapia Psicanalítica/métodosRESUMO
Resistance to permethrin in an East African population of the major malaria vector, Anopheles gambiae is multifactorial. A mutated sodium channel allele and enhanced insecticide metabolism contribute to the resistance phenotype. We used microsatellite markers to scan the genome for quantitative trait loci (QTL) associated with permethrin resistance. Two major and one minor QTL were identified. The first QTL, rtp1, colocalizes with the sodium channel gene on chromosome 2L thus further supporting the importance of mutations in this gene in conferring permethrin resistance. The second two loci are located on the third chromosome and one of these, rtp2, flanks a large cluster of cytochrome P450 genes. Further detailed mapping of these regions will help elucidate the molecular mechanisms of metabolic resistance to insecticides.
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Anopheles/genética , Mapeamento Cromossômico , Permetrina/toxicidade , Animais , Anopheles/efeitos dos fármacos , Cruzamentos Genéticos , Primers do DNA , Resistência a Inseticidas/genética , Repetições de Microssatélites/genética , Mutação/genética , Locos de Características Quantitativas/genética , Canais de Sódio/genéticaRESUMO
OBJECTIVE: To estimate the prevalence of caseous lymphadenitis (CLA), determine the current usage of vaccines against CLA and to measure the effectiveness of these vaccines on sheep farms. DESIGN AND POPULATION: A survey was undertaken on 223 sheep flocks in New South Wales, Victoria and Western Australia. METHOD: The prevalence of CLA was measured by conventional inspection techniques at abattoirs in lines of sheep that could be traced back to a farm. Managers of the flocks were sent a questionnaire about their vaccine practices, management practices and knowledge of CLA. RESULTS: The average prevalence of CLA in adult sheep in these flocks was 26% and varied from 20% in Western Australia to 29% in New South Wales. About 43% of sheep producers used CLA vaccines; only 12% used them as recommended. Awareness of CLA was highest in Western Australia. More producers would use CLA vaccine if they knew the prevalence of CLA in their flock and producers obtained most information about CLA from vaccine resellers. CONCLUSIONS: Only 10 to 15% of producers are currently achieving effective CLA control through the use of recommended CLA vaccination programs. In Western Australian flocks more than 25% of effectively vaccinated ewes will be sent to abattoirs in the 2 to 3 years after this study. However, large decreases in the prevalence of CLA can be achieved by about 70% of producers by either making adjustments to their vaccination programs or buying a vaccine with a CLA component. Two or three key facts on effective CLA vaccination could be made available at the point of sale of vaccines and from abattoirs that reported the prevalence of CLA to farmers.
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Vacinas Bacterianas/administração & dosagem , Infecções por Corynebacterium/veterinária , Corynebacterium pseudotuberculosis/imunologia , Linfadenite/veterinária , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/prevenção & controle , Vacinação/veterinária , Animais , Infecções por Corynebacterium/epidemiologia , Infecções por Corynebacterium/prevenção & controle , Linfadenite/epidemiologia , Linfadenite/prevenção & controle , New South Wales/epidemiologia , Prevalência , Ovinos , Doenças dos Ovinos/etiologia , Inquéritos e Questionários , Vitória/epidemiologia , Austrália Ocidental/epidemiologiaRESUMO
OBJECTIVE: To examine the effects of management practices and environment on the prevalence of arthritis in lambs. DESIGN AND POPULATION: A case-control study was conducted on groups of lambs from 122 Western Australian sheep flocks. METHOD: Arthritis was diagnosed by visual assessment of lambs at abattoirs by qualified meat inspectors. The prevalence was estimated from data collected from producers on culling practices for arthritis. Data on management practices and environmental variables were collected by personal interview. Stepwise logistic regression was used to measure the effects of the most important factors on the prevalence of arthritis. RESULTS: Mulesing and shearing lambs increased the odds of high prevalence of arthritis by 7 (95% CI 1.9 - 25.6) and 4.3 (95% CI 0.9 - 19.6) times, respectively compared to unmarked and unshorn lambs. Lambs slaughtered between December and June had 3.7 (95% CI 0.8 - 16.6) times greater odds of having a high prevalence of arthritis than lambs slaughtered in the remainder of the year. CONCLUSIONS: This study indicates that, to decrease the risk of high prevalence of arthritis, lambs raised for meat production should not be mulesed or shorn. Recommended improvements to hygiene at mulesing such as the use of portable yards had little effect on the prevalence of arthritis.
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Criação de Animais Domésticos/métodos , Artrite Infecciosa/veterinária , Infecções por Erysipelothrix/epidemiologia , Infecções por Erysipelothrix/prevenção & controle , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/prevenção & controle , Animais , Animais Recém-Nascidos , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/prevenção & controle , Estudos de Casos e Controles , Erysipelothrix , Prevalência , Ovinos , Austrália Ocidental/epidemiologiaRESUMO
OBJECTIVE: To determine whether the spread of Corynebacterium pseudotuberculosis infection to sheep in dips could be controlled by increasing the time between shearing and dipping. DESIGN: A controlled treatment trial where only the time between shearing and dipping was varied. ANIMALS AND PROCEDURE: One hundred and ninety-five sheep were found to be negative for C. pseudotuberculosis exposure by assay of CLA toxin antibody, were divided into four treatment groups. Each was shorn at either 0, 2, 4 or 8 weeks before dipping in a solution containing C. pseudotuberculosis. Blood samples were taken 6 weeks after dipping and sheep were slaughtered 12 weeks after dipping. A fifth smaller group of 14 sheep shorn 26 weeks before dipping, was also exposed to C. pseudotuberculosis and was slaughtered with the other sheep. RESULTS: The occurrence of caseous lymphadenitis abscesses did not differ between groups or with sheep shorn 26 weeks before dipping. The proportion of sheep that seroconverted to the C. pseudotuberculosis toxin and cell wall ELISA was larger in sheep dipped immediately after shearing than in sheep in the other groups. CONCLUSIONS: Delaying dipping until 8 weeks after shearing did not decrease the C. pseudotuberculosis infection rate due to dipping. Sheep dipped immediately after shearing developed higher concentrations of antibody to C. pseudotuberculosis than sheep when dipping occurred between 2 and 8 weeks and later after shearing.
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Criação de Animais Domésticos/métodos , Infecções por Corynebacterium/veterinária , Corynebacterium pseudotuberculosis , Transmissão de Doença Infecciosa/veterinária , Doenças dos Ovinos/transmissão , Animais , Anticorpos Antibacterianos/sangue , Toxinas Bacterianas , Infecções por Corynebacterium/sangue , Infecções por Corynebacterium/microbiologia , Infecções por Corynebacterium/transmissão , Corynebacterium pseudotuberculosis/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Linfadenite/sangue , Linfadenite/microbiologia , Linfadenite/veterinária , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/microbiologia , Fatores de TempoRESUMO
Slabs of slow-release plastic (Elvax) containing NMDA or solvent were implanted over the rat colliculus beginning on postnatal day 8 (P8). Whole-cell patch clamping in the superficial superior collicular layers (sSCs) from P10 to P21 demonstrated a severe decrease in spontaneous EPSC frequency after chronic NMDA treatment. The decrease was not attributable to an increase in GABA(A) receptor-mediated inhibition and was present only when NMDA receptor (NMDAR) current was blocked by Mg(2+). Analysis of miniature EPSCs indicated that many active sites on NMDA-treated neurons lacked functional AMPA and kainate receptor (AMPA/KAR) currents, and AMPA/KAR:NMDAR current ratios of evoked EPSCs were also significantly reduced. In addition, the normal downregulation of NMDAR decay time in sSC neurons at P11 was absent after NMDA treatment. Nevertheless, neither AMPA nor NMDA receptor subunit expression was altered by NMDA treatment, and experiments with the NMDAR antagonist ifenprodil suggested that incorporation of NR2A-containing NMDARs at the sSC synapses was unperturbed. Thus, disrupting but not blocking NMDARs suppresses the development of AMPA/KAR currents. The absence of the P11 NMDAR current downregulation is likely a secondary effect resulting from the reduction of AMPA/KAR function. Chronic agonist application reduces but does not eliminate NMDAR conductances. Therefore these data support an active role for NMDAR currents in synaptic development. Prolonged NMDA treatment in vivo, which couples reduced postsynaptic Ca(2+) responses with normally developing afferent activity, produces a long-lasting synaptic depression and stalls glutamatergic synaptogenesis, suggesting that the correlation between robust NMDAR activation and afferent activity is an essential component during normal development.
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Envelhecimento/metabolismo , Ácido Glutâmico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Colículos Superiores/metabolismo , Transmissão Sináptica/fisiologia , Animais , Animais Recém-Nascidos , Regulação para Baixo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Antagonistas de Receptores de GABA-A , Técnicas In Vitro , Magnésio/farmacologia , N-Metilaspartato/farmacologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/metabolismo , Receptores de GABA-A/metabolismo , Receptores de Ácido Caínico/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Colículos Superiores/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Transmissão Sináptica/efeitos dos fármacosRESUMO
INTRODUCTION AND OBJECTIVES: The induction of ventricular arrhythmias by appropriate antibradycardia ventricular pacing in patients with implantable cardioverter defibrillators has been reported in only a few cases. The aim of this study was to assess the incidence, characteristics and management of these episodes. METHODS: The follow-up records of 180 patients with implantable cardioverter defibrillators with intracardiac electrogram storage were reviewed. Pacing induced episodes were defined as those occurring immediately after an appropriate paced stimulus in a patient with sporadic paced beats. We assessed the number and type of episodes, mode of onset, therapy administered and the efficacy of different prevention measures. RESULTS: Pacing induced episodes were found in 9 patients (5%). Seven received device administered therapy which was effective in all cases. One to 95 episodes were observed per patient, of which 138 were monomorphic ventricular tachycardias and 20 polymorphic ventricular tachycardia/ventricular fibrillation episodes. All were induced by a paced ventricular beat after a post-extrasystolic pause or after long RR intervals during atrial fibrillation. Pacing induced arrhythmias were prevented by changing the pacing rate or hysteresis in 3 out of 6 patients and by decreasing the stimulus energy in 3 out of 3. Antibradycardia pacing function was disabled in 4 patients. CONCLUSIONS: Ventricular arrhythmias induced by appropriate antibradycardia ventricular pacing are relatively common in patients with implantable cardioverter defibrillators. Effective prevention can be achieved in most cases by changing the pacing rate or the pacing stimulus energy, however in selected cases the antibradycardia function may be disabled.
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Arritmias Cardíacas/etiologia , Bradicardia/terapia , Desfibriladores Implantáveis/efeitos adversos , Idoso , Arritmias Cardíacas/epidemiologia , Ventrículos do Coração , Humanos , Incidência , Masculino , Estudos RetrospectivosRESUMO
We have investigated the role of the NMDA glutamate receptor (NMDAR) in the genesis and regulation of structural plasticity during synaptogenesis in the visual layers of the rat superior colliculus (sSC). In this neuropil, three projections compete for synaptic space during development. By fluorescently labeling the projections of both eyes and imaging them with confocal microscopy, we can quantify the sprouting of the ipsilateral retinal projection that follows removal of a portion of the contralateral retinal and/or corticocollicular projection. Using these techniques we have studied the effects of NMDAR blockade under different levels of competition. NMDARs were chronically blocked from birth [postnatal day 0 (P0)] by suspending the competitive antagonist 2-amino-5-phosphonopentanoic acid in the slow release plastic Elvax, a slab of which was implanted over the sSC. Such treatment alone does not impair the normal segregation of the retinal projections. However, if sprouting of the ipsilateral projection is initiated with a small contralateral retinal lesion at P6, this sprouting can be further increased by blocking NMDARs from birth. Sprouting of the ipsilateral retinal projection is also induced by retinal lesions made at P10/P11, but NMDAR blockade does not augment the sprouting induced by this later lesion. However, when combined with simultaneous ablation of the ipsilateral visual cortex, P10/P11 lesions show increased sprouting after NMDAR blockade. These data indicate that P0 NMDAR blockade does not eliminate synaptic competition in the sSC. Instead, early elimination of NMDAR function appears to facilitate sprouting that is gated in a stepwise manner by the other visual afferents.
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Axônios/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Retina/citologia , Colículos Superiores/citologia , Vias Visuais/fisiologia , 2-Amino-5-fosfonovalerato/administração & dosagem , Animais , Animais Recém-Nascidos , Axônios/efeitos dos fármacos , Contagem de Células , Descorticação Cerebral , Implantes de Medicamento , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Corantes Fluorescentes , Plasticidade Neuronal/fisiologia , Lobo Occipital/fisiologia , Lobo Occipital/cirurgia , Ratos , Ratos Sprague-Dawley , Retina/fisiologia , Células Ganglionares da Retina/citologia , Escotoma , Vias Visuais/efeitos dos fármacos , Vias Visuais/crescimento & desenvolvimentoRESUMO
Whole-cell recording in the superficial layers of the developing superior colliculus (sSC) reveals a large drop in NMDA receptor (NMDAR) current decay time synchronized across all neurons and occurring consistently between P10 and P11. We show that blocking the Ca2+/calmodulin-dependent phosphatase calcineurin (CaN) in the postsynaptic neuron can abolish this drop. The regulation is induced prematurely by 1-2 hr of electrical stimulation in P10 collicular slices only if CaN and NMDAR currents can be activated in the neuron. These data suggest that a long-lasting, CaN-mediated control of NMDAR kinetics is rapidly initiated by heightened activity of the NMDAR itself and demonstrate a novel developmental and tonic function of CaN that can play an important role in modulating the plasticity of the developing CNS.