RESUMEN
The COVID-19 pandemic has highlighted the importance of environmental ventilation in reducing airborne pathogen transmission. Carbon dioxide monitoring is recommended in the community to ensure adequate ventilation. Dynamic measurements of ventilation quantifying human exhaled waste gas accumulation are not conducted routinely in hospitals. Instead, environmental ventilation is allocated using static hourly air change rates. These vary according to the degree of perceived hazard, with the highest change rates reserved for locations where aerosol-generating procedures are performed, where medical/anaesthetic gases are used and where a small number of high-risk infective or immunocompromised patients may be isolated to reduce cross-infection. We aimed to quantify the quality and distribution of ventilation in hospital by measuring carbon dioxide levels in a two-phased prospective observational study. First, under controlled conditions, we validated our method and the relationship between human occupancy, ventilation and carbon dioxide levels using non-dispersive infrared carbon dioxide monitors. We then assessed ventilation quality in patient-occupied (clinical) and staff break and office (non-clinical) areas across two hospitals in Scotland. We selected acute medical and respiratory wards in which patients with COVID-19 are cared for routinely, as well as ICUs and operating theatres where aerosol-generating procedures are performed routinely. Between November and December 2022, 127,680 carbon dioxide measurements were obtained across 32 areas over 8 weeks. Carbon dioxide levels breached the 800 ppm threshold for 14% of the time in non-clinical areas vs. 7% in clinical areas (p < 0.001). In non-clinical areas, carbon dioxide levels were > 800 ppm for 20% of the time in both ICUs and wards, vs. 1% in operating theatres (p < 0.001). In clinical areas, carbon dioxide was > 800 ppm for 16% of the time in wards, vs. 0% in ICUs and operating theatres (p < 0.001). We conclude that staff break, office and clinical areas on acute medical and respiratory wards frequently had inadequate ventilation, potentially increasing the risks of airborne pathogen transmission to staff and patients. Conversely, ventilation was consistently high in the ICU and operating theatre clinical environments. Carbon dioxide monitoring could be used to measure and guide improvements in hospital ventilation.
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COVID-19 , Dióxido de Carbono , Humanos , Pandemias , Aerosoles y Gotitas Respiratorias , HospitalesRESUMEN
This study investigates the inter-trial variability of saccade trajectories observed in five rhesus macaques (Macaca mulatta). For each time point during a saccade, the inter-trial variance of eye position and its covariance with eye end position were evaluated. Data were modeled by a superposition of three noise components due to 1) planning noise, 2) signal-dependent motor noise, and 3) signal-dependent premotor noise entering within an internal feedback loop. Both planning noise and signal-dependent motor noise (together called accumulating noise) predict a simple S-shaped variance increase during saccades, which was not sufficient to explain the data. Adding noise within an internal feedback loop enabled the model to mimic variance/covariance structure in each monkey, and to estimate the noise amplitudes and the feedback gain. Feedback noise had little effect on end point noise, which was dominated by accumulating noise. This analysis was further extended to saccades executed during inactivation of the caudal fastigial nucleus (cFN) on one side of the cerebellum. Saccades ipsiversive to an inactivated cFN showed more end point variance than did normal saccades. During cFN inactivation, eye position during saccades was statistically more strongly coupled to eye position at saccade end. The proposed model could fit the variance/covariance structure of ipsiversive and contraversive saccades. Inactivation effects on saccade noise are explained by a decrease of the feedback gain and an increase of planning and/or signal-dependent motor noise. The decrease of the fitted feedback gain is consistent with previous studies suggesting a role for the cerebellum in an internal feedback mechanism. Increased end point variance did not result from impaired feedback but from the increase of accumulating noise. The effects of cFN inactivation on saccade noise indicate that the effects of cFN inactivation cannot be explained entirely with the cFN's direct connections to the saccade-related premotor centers in the brainstem.
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Núcleos Cerebelosos/fisiología , Modelos Neurológicos , Neuronas Motoras/fisiología , Movimientos Sacádicos/fisiología , Animales , Simulación por Computador , Retroalimentación Sensorial/fisiología , Humanos , Macaca mulatta , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Perineuronal nets (PNNs) are extracellular molecules that form around neurons near the end of critical periods during development. They surround neuronal cell bodies and proximal dendrites. PNNs inhibit the formation of new connections and may concentrate around rapidly firing inhibitory interneurons. Previous work characterized the important role of perineuronal nets in plasticity in the visual system, amygdala, and spinal cord of rats. In this study, we use immunohistochemistry to survey the distribution of perineuronal nets in representative areas of the primate brain. We also document changes in PNN prevalence in these areas in animals of different ages. We found that PNNs are most prevalent in the cerebellar nuclei, surrounding >90% of the neurons there. They are much less prevalent in cerebral cortex, surrounding less than 10% of neurons in every area that we examined. The incidence of perineuronal nets around parvalbumin-positive neurons (putative fast-spiking interneurons) varies considerably between different areas in the brain. Our survey indicates that the presence of PNNs may not have a simple relationship with neural plasticity and may serve multiple functions in the central nervous system.
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Acetilgalactosamina/análisis , Encéfalo/metabolismo , Matriz Extracelular/metabolismo , Plasticidad Neuronal , Neuronas/metabolismo , Animales , Encéfalo/citología , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Macaca mulatta , Masculino , Neuronas/citología , Ratas , Médula Espinal/citología , Médula Espinal/metabolismo , Sinapsis/metabolismoRESUMEN
To characterize the cerebellar influence on neurons in the abducens (ABD) nucleus, we recorded ABD neurons before and after we inactivated the caudal part of the ipsilateral cerebellar fastigial nucleus (cFN) with muscimol injection. cFN activity influences the horizontal component of saccades. cFN inactivation increased the activity of most ipsilateral ABD neurons (19/22 in 2 monkeys) during ipsiversive (hypermetric) saccades, primarily by increasing burst duration. During contraversive (hypometric) saccades, the off-direction pause of most (10/15) ABD neurons was shorter than normal because of the early resumption of ABD activity. Early ABD firing caused the early contraction of antagonist muscles that reduced eye rotation and made contraversive saccades hypometric. Thus the cerebellum controls ipsilateral ABD activity by truncating on-direction bursts during ipsiversive saccades and extending off-direction pauses during contraversive saccades. We conclude that cFN output keeps saccades accurate by controlling when ABD on-direction bursts and off-direction pauses end.
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Núcleo del Nervio Abducens/fisiología , Núcleos Cerebelosos/fisiología , Neuronas/fisiología , Movimientos Sacádicos/fisiología , Animales , Macaca mulatta , MasculinoRESUMEN
From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the earliest stage of the visual process. In primates, by contrast, direction selectivity is a hallmark of motion processing areas in visual cortex, but has not been found in the retina, despite significant effort. Here we combined functional recordings of light-evoked responses and connectomic reconstruction to identify diverse direction-selective cell types in the macaque monkey retina with distinctive physiological properties and synaptic motifs. This circuitry includes an ON-OFF ganglion cell type, a spiking, ON-OFF polyaxonal amacrine cell and the starburst amacrine cell, all of which show direction selectivity. Moreover, we discovered that macaque starburst cells possess a strong, non-GABAergic, antagonistic surround mediated by input from excitatory bipolar cells that is critical for the generation of radial motion sensitivity in these cells. Our findings open a door to investigation of a precortical circuitry that computes motion direction in the primate visual system.
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Conectoma , Macaca , Retina , Células Amacrinas/fisiología , Animales , Potenciales Evocados Visuales/fisiología , Macaca/fisiología , Mamíferos , Ratones , Primates/fisiología , Retina/fisiología , Células Ganglionares de la Retina/fisiología , Sinapsis/fisiologíaRESUMEN
Human vision starts with the activation of rod photoreceptors in dim light and short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway, arising from a population of retinal ganglion cells, was discovered in nocturnal rodents. These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction. Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and (L + M) cone-derived light responses combine in these giant cells to signal irradiance over the full dynamic range of human vision. In accordance with cone-based colour opponency, the giant cells project to the lateral geniculate nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception.
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Percepción de Color/fisiología , Macaca/fisiología , Células Ganglionares de la Retina/fisiología , Opsinas de Bastones/metabolismo , Núcleos Talámicos/fisiología , Animales , Células Cultivadas , Oscuridad , Humanos , Técnicas In Vitro , Luz , Fototransducción/efectos de la radiación , Retina/citología , Retina/fisiología , Retina/efectos de la radiación , Células Fotorreceptoras Retinianas Conos/fisiología , Células Fotorreceptoras Retinianas Conos/efectos de la radiación , Células Ganglionares de la Retina/citología , Células Ganglionares de la Retina/efectos de la radiación , Células Fotorreceptoras Retinianas Bastones/fisiología , Células Fotorreceptoras Retinianas Bastones/efectos de la radiación , Opsinas de Bastones/genética , Núcleos Talámicos/efectos de la radiación , Vías Visuales/fisiología , Vías Visuales/efectos de la radiaciónRESUMEN
OBJECTIVE: An analysis of surgical experience in gastrointestinal procedures within a UK-based gynaecological oncology centre to which subspecialty fellows within the subject are exposed. DESIGN: Retrospective study. SETTING: Northern Gynaecological Oncology Centre, Gateshead, UK. POPULATION: All women undergoing bowel surgery over a six-year period, 1 January 2000 to 31 December 2005. METHODS: Cases were analysed by specialty and grade of surgeon performing the procedure. MAIN OUTCOME MEASURE: Proportion of cases to which subspecialty fellows were exposed. RESULTS: Two hundred and sixty-two women (11.5%) underwent bowel surgery out of 2280 women undergoing major surgery for gynaecological cancer. This included ovarian/primary peritoneal cancer in 186 women (71%). Of these 262 cases, 238 operations (91%) were performed by a gynaecological oncologist, 20 (7.5%) were performed jointly with the gastrointestinal surgeons and four (1.5%) were performed solely by the gastrointestinal surgeons. A gynaecological oncology subspecialty fellow performed 21 (8%) and assisted in an additional 204 operations (78%). Perioperative morbidity and mortality statistics in addition to overall survival outcomes were comparable to the published literature. CONCLUSIONS: A significant proportion of major surgical operations performed within a gynaecological oncology centre require gastrointestinal procedures. The majority of these procedures can be performed by gynaecological oncologists with an acceptable perioperative morbidity and mortality rate. Subspecialty training has the potential to allow trainees significant exposure to these procedures. An accredited post-Fellowship Training Programme can provide the opportunity for hands-on experience to allow gynaecological oncologists the confidence and credibility to perform these procedures independently.
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Neoplasias de los Genitales Femeninos/cirugía , Enfermedades Intestinales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Femenino , Gastroenterología/estadística & datos numéricos , Ginecología/estadística & datos numéricos , Humanos , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Estudios Retrospectivos , Reino Unido , Adulto JovenRESUMEN
BACKGROUND/AIMS: Posterior fossa tumors are the most common brain tumors in children. Surgeons usually remove these tumors via a midline incision through the posterior vermis of the cerebellum. Though often effective, this surgery causes hypotonia, ataxia, oculomotor deficits, transient mutism, difficulty in swallowing and nausea. To date, there is no animal model that mimics these complications. We found that the rhesus macaque is a good model for the consequences of this surgery. METHODS: We made a midline incision through the cerebellar vermis of one monkey to mimic the posterior fossa surgery. Then, we closely monitored the monkey for deficits following the surgery. RESULTS: In the first few days, the monkey exhibited nausea, hypotonia, ataxia, difficulty in swallowing and an absence of vocalization. At 28 days, we recorded eye movements and found severe deficits in the accuracy of rapid eye movements and smooth pursuit of a target. Additionally, the animal had trouble fixating and a rightward-beating nystagmus. Oculomotor signs persisted until we sacrificed the animal 99 days after surgery, but the other effects resolved by 37 days. CONCLUSION: Our surgery in a monkey caused the same postsurgical signs observed in humans. We expect to use this model to improve the posterior fossa surgery methods.
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Modelos Animales de Enfermedad , Neoplasias Infratentoriales/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Animales , Neoplasias Infratentoriales/fisiopatología , Macaca mulatta , Masculino , Hipotonía Muscular/diagnóstico , Hipotonía Muscular/etiología , Hipotonía Muscular/fisiopatología , Mutismo/diagnóstico , Mutismo/etiología , Mutismo/fisiopatología , Complicaciones Posoperatorias/etiología , SíndromeRESUMEN
The distinctive parasol ganglion cell of the primate retina transmits a transient, spectrally nonopponent signal to the magnocellular layers of the lateral geniculate nucleus. Parasol cells show well-recognized parallels with the alpha-Y cell of other mammals, yet two key alpha-Y cell properties, a collateral projection to the superior colliculus and nonlinear spatial summation, have not been clearly established for parasol cells. Here, we show by retrograde photodynamic staining that parasol cells project to the superior colliculus. Photostained dendritic trees formed characteristic spatial mosaics and afforded unequivocal identification of the parasol cells among diverse collicular-projecting cell types. Loose-patch recordings were used to demonstrate for all parasol cells a distinct Y-cell receptive field "signature" marked by a nonlinear mechanism that responded to contrast-reversing gratings at twice the stimulus temporal frequency [second Fourier harmonic (F2)] independent of stimulus spatial phase. The F2 component showed high contrast gain and temporal sensitivity and appeared to originate from a region coextensive with that of the linear receptive field center. The F2 spatial frequency response peaked well beyond the resolution limit of the linear receptive field center, showing a Gaussian center radius of approximately 15 microm. Blocking inner retinal inhibition elevated the F2 response, suggesting that amacrine circuitry does not generate this nonlinearity. Our data are consistent with a pooled-subunit model of the parasol Y-cell receptive field in which summation from an array of transient, partially rectifying cone bipolar cells accounts for both linear and nonlinear components of the receptive field.
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Macaca/anatomía & histología , Células Ganglionares de la Retina/citología , Colículos Superiores/citología , Campos Visuales , Vías Visuales/citología , Animales , Macaca/fisiología , Macaca fascicularis , Macaca mulatta , Macaca nemestrina , Papio , Estimulación Luminosa/métodos , Retina/citología , Retina/fisiología , Células Ganglionares de la Retina/clasificación , Células Ganglionares de la Retina/fisiología , Colículos Superiores/fisiología , Campos Visuales/fisiología , Vías Visuales/fisiologíaRESUMEN
In the primate visual system approximately 20 morphologically distinct pathways originate from retinal ganglion cells and project in parallel to the lateral geniculate nucleus (LGN) and/or the superior colliculus. Understanding of the properties of these pathways and the significance of such extreme early pathway diversity for later visual processing is limited. In a companion study we found that the magnocellular LGN-projecting parasol ganglion cells also projected to the superior colliculus and showed Y-cell receptive field structure supporting the hypothesis that the parasol cells are analogous to the well studied alpha-Y cell of the cat's retina. We here identify a novel ganglion cell class, the smooth monostratified cells, that share many properties with the parasol cells. Smooth cells were retrogradely stained from tracer injections made into either the LGN or superior colliculus and formed inner-ON and outer-OFF populations with narrowly monostratified dendritic trees that surprisingly appeared to perfectly costratify with the dendrites of parasol cells. Also like parasol cells, smooth cells summed input from L- and M-cones, lacked measurable S-cone input, showed high spike discharge rates, high contrast and temporal sensitivity, and a Y-cell type nonlinear spatial summation. Smooth cells were distinguished from parasol cells however by smaller cell body and axon diameters but approximately 2 times larger dendritic tree and receptive field diameters that formed a regular but lower density mosaic organization. We suggest that the smooth and parasol populations may sample a common presynaptic circuitry but give rise to distinct, parallel achromatic spatial channels in the primate retinogeniculate pathway.
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Axones/ultraestructura , Cuerpos Geniculados/citología , Células Ganglionares de la Retina/citología , Colículos Superiores/citología , Vías Visuales/citología , Percepción Visual/fisiología , Potenciales de Acción/fisiología , Animales , Axones/fisiología , Forma de la Célula/fisiología , Dendritas/fisiología , Dendritas/ultraestructura , Dextranos , Cuerpos Geniculados/fisiología , Macaca mulatta , Dinámicas no Lineales , Orientación/fisiología , Células Ganglionares de la Retina/fisiología , Rodaminas , Percepción Espacial/fisiología , Coloración y Etiquetado , Colículos Superiores/fisiología , Sinapsis/fisiología , Sinapsis/ultraestructura , Campos Visuales/fisiología , Vías Visuales/fisiologíaRESUMEN
Diverse cell types and parallel pathways are characteristic of the vertebrate nervous system, yet it remains a challenge to define the basic components of most neural structures. We describe a process termed retrograde photodynamics that allowed us to rapidly make the link between morphology, physiology, and connectivity for ganglion cells in the macaque retina that project to the lateral geniculate nucleus (LGN). Rhodamine dextran injected into the LGN was transported retrogradely and sequestered within the cytoplasm of ganglion cell bodies. Exposure of the retina to light in vitro liberated the tracer and allowed it to diffuse throughout the dendrites, revealing the cell's complete morphology. Eight previously unknown LGN-projecting cell types were identified. Cells could also be targeted in vitro for intracellular recording and physiological analysis. The photodynamic process was also observed in pyramidal cells in a rat neocortical slice.
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Biotina/análogos & derivados , Dendritas/ultraestructura , Dextranos , Microscopía Fluorescente/métodos , Estimulación Luminosa/métodos , Células Ganglionares de la Retina/citología , Rodaminas , Potenciales de Acción/fisiología , Animales , Transporte Axonal/efectos de los fármacos , Transporte Axonal/fisiología , Dendritas/fisiología , Difusión/efectos de los fármacos , Cuerpos Geniculados/citología , Cuerpos Geniculados/fisiología , Macaca , Microscopía Fluorescente/instrumentación , Técnicas de Cultivo de Órganos , Estimulación Luminosa/instrumentación , Células Piramidales/citología , Células Piramidales/fisiología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Células Ganglionares de la Retina/clasificación , Células Ganglionares de la Retina/fisiología , Corteza Visual/citología , Corteza Visual/fisiología , Vías Visuales/citología , Vías Visuales/fisiologíaRESUMEN
Perineuronal nets (PNNs) accumulate around neurons near the end of developmental critical periods. PNNs are structures of the extracellular matrix which surround synaptic contacts and contain chondroitin sulfate proteoglycans. Previous studies suggest that the chondroitin sulfate chains of PNNs inhibit synaptic plasticity and thereby help end critical periods. PNNs surround a high proportion of neurons in the cerebellar nuclei. These PNNs form during approximately the same time that movements achieve normal accuracy. It is possible that PNNs in the cerebellar nuclei inhibit plasticity to maintain the synaptic organization that produces those accurate movements. We tested whether or not PNNs in a saccade-related part of the cerebellar nuclei maintain accurate saccade size by digesting a part of them in an adult monkey performing a task that changes saccade size (long term saccade adaptation). We use the enzyme Chondroitinase ABC to digest the glycosaminoglycan side chains of proteoglycans present in the majority of PNNs. We show that this manipulation does not result in faster, larger, or more persistent adaptation. Our result indicates that intact perineuronal nets around saccade-related neurons in the cerebellar nuclei are not important for maintaining long-term saccade gain.
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Acetilgalactosamina/metabolismo , Núcleos Cerebelosos/fisiología , Red Nerviosa/fisiología , Movimientos Sacádicos/fisiología , Adaptación Ocular/fisiología , Adaptación Fisiológica/fisiología , Animales , Condroitina ABC Liasa/metabolismo , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/fisiología , Macaca mulatta , Masculino , Red Nerviosa/metabolismo , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Neuronas/fisiología , Factores de TiempoRESUMEN
Copper (Cu) metabolism is altered in rats fed diets high in molybdenum (Mo) and low in Cu. This 10-week study was carried out to examine the effects of supplemental Mo (7.5-240 µg/g diet) on male Sprague-Dawley rats fed diets adequate in Cu (5 µg/g diet) and to determine the susceptibility of Mo-treated animals to the environmental pollutant 3,3',4,4'-tetrabromobiphenyl (TBB). After 7 weeks of dietary treatment, half of the rats in each group received a single IP injection of TBB (150 µM/kg bw), while the other half received the corn oil vehicle. Rats sacrificed at 10 weeks showed no effects of Mo on growth, feed efficiency, or selected organ or tissue weights. Dose-dependent effects on plasma Mo (0-5.1 µg/mL), plasma Cu (0.95-0.20 µg/mL), and bone Cu (3.4-10 µg/g) in control through the high dose were found. Cu sequestration in the bone of Mo-treated rats is a new finding. TBB treatment resulted in dramatic weight loss and loss of absolute organ mass. Relative organ weights were increased, except for the thymus. TBB altered the concentrations of certain amino acids. Compared to control rats, this polybrominated biphenyl congener significantly decreased plasma Cu and ceruloplasmin at higher concentrations of dietary Mo and promoted the process of plasma Cu decrease by Mo, suggesting a combined effect.
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Cobre/toxicidad , Sustancias Peligrosas/toxicidad , Molibdeno/toxicidad , Bifenilos Polibrominados/toxicidad , Animales , Ceruloplasmina/metabolismo , Cobre/metabolismo , Dieta , Suplementos Dietéticos , Sustancias Peligrosas/administración & dosificación , Sustancias Peligrosas/metabolismo , Inyecciones Intraperitoneales , Masculino , Molibdeno/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Bifenilos Polibrominados/administración & dosificación , Bifenilos Polibrominados/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The caudal part of the cerebellar fastigial nucleus (CFN) influences the horizontal component of saccades. Previous reports show that activity in the CFN contralateral to saccade direction aids saccade acceleration and that activity in the ipsilateral CFN aids saccade deceleration. Here we refine this description by characterizing how blocking CFN activity changes the distance that the eye rotates during each of 4 phases of saccades, the increasing and decreasing saccade acceleration (phases 1 and 2) and deceleration (3 and 4). We found that unilateral CFN inactivation increases total eye rotation to â¼1.8× normal. This resulted from rotation increases in all four phases of ipsiversive saccades. Rotation during phases 1 and 2 increases slightly, more during phase 3, and most during phase 4, to â¼4.4× normal. Thus, the ipsilateral CFN normally reduces eye rotation throughout a saccade but reduces it the most near saccade end. After unilateral CFN inactivation, rotation during contraversive saccades was â¼0.8× normal. This resulted from decreased rotation during phases 1-3, to â¼0.7× normal, and then normal rotation during phase 4. Thus the CFN contraversive to saccade direction normally increases eye rotation during acceleration and the first phase of deceleration. These data indicate that the influences of the CFNs on saccades overlap extensively and that there is a smooth shift from predominance of the contralateral CFN early in a saccade to the ipsilateral CFN later. The pathway from the CFN to contralateral IBNs and then to the abducens nucleus can account for these effects.
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Núcleos Cerebelosos/fisiología , Orientación/fisiología , Movimientos Sacádicos/fisiología , Vías Visuales/fisiología , Animales , Ataxia Cerebelosa/fisiopatología , Núcleos Cerebelosos/efectos de los fármacos , Lateralidad Funcional/efectos de los fármacos , Lateralidad Funcional/fisiología , Agonistas de Receptores de GABA-A/farmacología , Macaca mulatta , Muscimol/farmacología , Orientación/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Movimientos Sacádicos/efectos de los fármacos , Factores de Tiempo , Vías Visuales/efectos de los fármacosRESUMEN
The caudal fastigial nucleus (cFN) is one of the main cerebellar areas involved in the control of eye movements. Lesions of this area cause hypermetria of ipsilateral saccades and hypometria of contralateral saccades, as well as cogwheel smooth pursuit. Most studies with nonhuman primates described this dysmetria with a change of the ratio target amplitude to saccade amplitude, whereas in cats this dysmetria was attributed to a static fixation error. The targeting of visually-guided saccades before and after 11 unilateral injections of the inhibitory transmitter muscimol into the caudal fastigial nucleus in 5 monkeys was analyzed. In one monkey, who had eye coils implanted in both eyes, the postsaccadic interocular alignment was also analyzed. The main result is that the dysmetria observed in nonhuman primates can be explained as a combination of (1) hypermetria of the ipsilateral horizontal saccade component, and (2) a horizontal static fixation error of about 1.2 deg toward the side of the lesion. The static postsaccadic alignment of both eyes was only slightly disturbed after unilateral injection. The results suggest that the dysmetria seen after muscimol inactivation of the cFN is due to two distinct processes: one causes a gain change, and the other causes the static fixation error. Unilateral lesions have only a slight influence on binocular postsaccadic alignment.
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Núcleos Cerebelosos/patología , Macaca mulatta/fisiología , Movimientos Sacádicos , AnimalesRESUMEN
Cerebellar output changes during motor learning. How these changes cause alterations of motoneuron activity and movement remains an unresolved question for voluntary movements. To answer this question, we examined premotor neurons for saccadic eye movement. Previous studies indicate that cells in the fastigial oculomotor region (FOR) within the cerebellar nuclei on one side exhibit a gradual increase in their saccade-related discharge as the amplitude of ipsiversive saccades adaptively decreases. This change in FOR activity could cause the adaptive change in saccade amplitude because neurons in the FOR project directly to the brain stem region containing premotor burst neurons (BNs). To test this possibility, we recorded the activity of saccade-related burst neurons in the area that houses premotor inhibitory burst neurons (IBNs) and examined their discharge during amplitude-reducing adaptation elicited by intrasaccadic target steps. We specifically analyzed their activity for off-direction (contraversive) saccades, in which the IBN activity would increase to reduce saccade size. Before adaptation, 29 of 42 BNs examined discharged, at least occasionally, for contraversive saccades. As the amplitude of contraversive saccades decreased adaptively, half of BNs with off-direction spike activity showed an increase in the number of spikes (14/29) or an earlier occurrence of spikes (7/14). BNs that were silent during off-direction saccades before adaptation remained silent after adaptation. These results indicate that the changes in the off-direction activity of BNs are closely related to adaptive changes in saccade size and are appropriate to cause these changes.
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Adaptación Fisiológica/fisiología , Tronco Encefálico/fisiología , Interneuronas/fisiología , Red Nerviosa/fisiología , Inhibición Neural/fisiología , Movimientos Sacádicos/fisiología , Nervio Abducens/fisiología , Potenciales de Acción/fisiología , Animales , Tronco Encefálico/anatomía & histología , Núcleos Cerebelosos/anatomía & histología , Núcleos Cerebelosos/fisiología , Fijación Ocular/fisiología , Macaca mulatta , Neuronas Motoras/fisiología , Red Nerviosa/anatomía & histología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Músculos Oculomotores/inervación , Músculos Oculomotores/fisiología , Orientación/fisiología , Desempeño Psicomotor/fisiología , Transducción de Señal/fisiología , Percepción Espacial/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
In monkeys, saccades that repeatedly overshoot their targets adapt to become smaller by the time the monkey has made 1,000-2,000 saccades. In life, adaptation must keep movements accurate for long periods of time. Previous work describes only saccade adaptation that occurs within a few hours. Here we describe long-term saccade adaptation elicited in three monkeys by 19 days of training. Each day a monkey made saccades to track 16 degrees leftward and rightward target movements. During saccades, the target stepped back toward its starting position 6.4 degrees (40%) in two monkeys or 8 degrees (50%) in the third. After each day's adaptation, we blindfolded the monkey with goggles and returned it to its cage overnight. We found that adapting saccades for 19 days elicited significantly larger, long-lasting reduction in saccade size than did adapting for only 1 day. Further, after 19 days of adaptation we could elicit additional, apparently normal, short-term reduction in saccade size by increasing the size of the intra-saccade target movement. In contrast, we could elicit only small additional size reduction after only 1 day of adaptation. A simple model using separate short- and long-term adaptation mechanisms can reproduce many of the features of saccade gain exhibited by monkeys during a 19-day adaptation. We conclude that there is a long-term saccade-adaptation mechanism that is distinct from the well-characterized short-term system and that this newly recognized system is responsible for long-term maintenance of saccade accuracy.
Asunto(s)
Movimientos Sacádicos/fisiología , Aclimatación , Adaptación Ocular , Animales , Macaca mulatta , Masculino , Seguimiento Ocular Uniforme/fisiologíaRESUMEN
Saccades that consistently over- or undershoot their targets gradually become smaller or larger, respectively. The signal that elicits adaptation of saccade size is a difference between eye and target positions appearing repeatedly at the ends of saccades. Here we describe how visual error size affects the size of saccade adaptation. At the end of each saccade, we imposed a constant-sized error by moving the target to a specified point relative to eye position. We tested a variety of error sizes imposed after saccades to target movements of 6, 12, and 18 degrees. We found that the size of the gain change elicited in a particular experiment depended on both the size of the imposed postsaccade error and on the size of the preceding target movement. For example, imposed errors of 4-5 degrees reduce saccades tracking 6, 12, and 18 degrees target movements by an average of 18, 35, and 45%, respectively. The most effective errors were those that were 15-45% of the size of the initial target eccentricity. Negative errors, which reduce saccade size, were more effective in changing saccade gain than were positive errors, which increased saccade size. For example, for 12 degrees target movements, negative and positive errors of 2-6 degrees changed saccade gain an average of 35 and 8%, respectively. This description of the relationship between error size and adaptation size improves our ability to adapt saccades in the laboratory and characterizes the error sizes that will best drive neurons carrying the adaptation-related visual error signal.
Asunto(s)
Adaptación Fisiológica , Macaca mulatta , Movimientos Sacádicos/fisiología , Percepción Visual/fisiología , Animales , Masculino , Estimulación LuminosaRESUMEN
We describe a family of Slovenian descent with progressive ataxia, corticospinal signs, axonal sensorimotor neuropathy, and disruption of visual fixation by saccadic intrusions. Chromosome mapping indicated a mutation on 1p36, and this recessive disorder has been designated spinocerebellar ataxia with saccadic intrusions. Affected patients showed overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades; other eye movements were normal. Slowed conduction in axons that are selectively vulnerable to the molecular defect could explain both the sensorimotor neuropathy and the saccadic disorder, which would be caused by delayed feedback control because of slow conduction in cerebellar parallel fibers.