21. Sustitución valvular aórtica: ¿prótesis biológica o mecánica? Estudio comparativo de sobrevida a largo plazo

Antecedentes: la elección del tipo de prótesis valvular en los pacientes sometidos a sustitución valvular aórtica (SVA) es de gran relevancia. Buscamos evaluar si es el tipo de prótesis valvular aórtica un predictor de mortalidad operatoria y sobrevida a largo plazo. Objetivo: el objetivo del trabajo es comparar el impacto de la colocación de prótesis valvulares mecánicas y biológicas en la mortalidad operatoria y sobrevida a largo plazo. Material y método: se identificaron en la base de datos de la institución aquellos pacientes sometidos a SVA entre enero de 2006 y diciembre de 2016. Se extrajeron y compararon las variables demográficas, intraoperatorias y posoperatorias. Se compararon las mismas entre aquellos que recibieron bioprótesis y prótesis mecánica mediante chi cuadrado (variables categóricas) y test de t (variables continuas). Se utilizó Kaplan-Meier y log-rank test para comparación de sobrevida. Mediante regresión logística y Cox se identificó el valor predictivo del tipo protésico en los resultados. Resultados: en dicho período se operaron 1.826 pacientes por SVA. Recibieron bioprótesis 1.450 pacientes (78,3%). Estos eran de mayor edad (72,7±8,5 versus 53,7±11,9, p<0,05), con mayor incidencia de CFNYHA III-IV, mayor requerimiento de revascularización asociada y mayor Euroscore (10,5±0,1 versus 7,7±0,1, p<0,05). Pacientes con prótesis mecánica presentaban mayor incidencia de tabaquismo, endocarditis y requerimiento de sustitución de aorta ascendente. No hubo diferencias en las variables intraoperatorias a excepción de menor tamaño de prótesis en el grupo de bioprótesis (22,1±2,0 versus 23,1±2,3, p<0,05). Pacientes con bioprótesis presentaron mayor incidencia de FA, accidente isquémico transitorio y requerimiento de inotrópicos. No hubo diferencias significativas en la mortalidad operatoria. A diez años de seguimiento, el tipo protésico no fue predictor de sobrevida a largo plazo. Conclusiones: el tipo de prótesis valvular aórtica no es predictor de mortalidad operatoria ni sobrevida a largo plazo.

Early surgery after angiography in patients scheduled for valve replacement.

Background There are limited data regarding the risks of cardiac surgery early after coronary angiography in patients scheduled for isolated aortic and/or mitral valve replacement. Our aim was to evaluate the risk of early surgery after coronary angiography in these patients. Methods We retrospectively analyzed data of 1044 patients who underwent isolated aortic and/or mitral valve replacement from 2006 to 2014. Baseline, operative, and postoperative variables were collected. The patients were divided into 3 groups based on the interval between coronary angiography and surgery: ≤3 days ( n = 216), 4-7 days ( n = 109), and ≥8 days ( n = 719). We evaluated hospital mortality and postoperative acute kidney injury. Subgroup analysis was performed according to preoperative creatinine clearance. Results Postoperative creatinine clearance was lower in patients who underwent surgery ≤3 days after coronary angiography (63.57 ± 38.52 mL min-1) compared to ≥8 days after coronary angiography (74.56 ± 54.25 mL min-1, p = 0.015). Patients who underwent surgery ≤3 days after coronary angiography had higher hospital mortality when preoperative creatinine clearance was ≤60 mL min-1 (12% vs. 4% for creatinine clearance ≤and >60 mL min-1, respectively; p = 0.039). Predictors of hospital mortality were New York Heart Association class and postoperative creatinine clearance. Conclusion Hospital mortality was higher in patients with decreased preoperative renal function who underwent surgery within the first 3 days after coronary angiography. Delaying surgery in this subgroup of patients could be a good strategy.

¿Es seguro realizar la cirugía de revascularización miocárdica precozmente luego del cateterismo? / Is it safe to perform coronary artery bypass surgery early after catheterization?

Fundamentos y objetivos: existen reportes que vinculan la cirugía coronaria precoz luego de la coronariografía a falla renal aguda posoperatoria. Sin embargo, no existe evidencia concluyente acerca de la relación directa entre cirugía coronaria precoz y mortalidad posoperatoria. Nuestro objetivo fue evaluar la relación entre la cirugía coronaria precoz (dentro de las 24 horas de la coronariografía) y la evolución posoperatoria. Método: se seleccionaron pacientes sometidos a cirugía de revascularización coronaria aislada operados entre enero de 2006 y diciembre de 2014. Comparamos las características demográficas entre los pacientes sometidos a cirugía precoz versus no precoz. Evaluamos las siguientes variables evolutivas: mortalidad operatoria, tiempo de asistencia ventilatoria, uso de inotrópicos, tiempo de internación en cuidados intensivos y requerimiento de hemodiálisis. Resultados: se incluyeron un total de 2.039 pacientes (cirugía precoz en 382). Aquellos operados dentro de las 24 horas eran más jóvenes, con menor proporción de mujeres y con mayor incidencia de ángor inestable e inestabilidad hemodinámica. La cirugía precoz resultó ser predictora de mortalidad operatoria solo en aquellos pacientes con creatinina preoperatoria ³ 1,2 mg/dl (OR=2,81; IC 95% 1,03-7,68). No encontramos asociación con el resto de las variables evolutivas a excepción del mayor uso prolongado de inotrópicos/vasopresores en pacientes sometidos a cirugía precoz. Conclusiones: la cirugía de revascularización aislada realizada precozmente luego de la coronariografía en pacientes con cifras normales de creatinina (menor a 1,2 mg/dl) puede ser realizada de forma segura y no se asocia a mayor mortalidad operatoria.

Objectives: cardiac surgery performed early after coronariography has been associated with acute renal failure. Nonetheless, there is no solid evidence regarding its association with operative mortality. Our objective was to evaluate the association between early coronary surgery and postoperative outcomes. Methods: patients who underwent isolated coronary artery revascularization between January 2006 and December 2014 were selected from our database. Baseline characteristics were compared between patients who underwent surgery within 24h of coronariography and those in whom surgery was performed afterwards. The following postoperative outcomes were extracted and compared between both groups: operative mortality, time of assisted ventilation, inotrope use, stay in intensive care unit, stay in intensive care unit, and hemodyalisis requirement. Results: we included 2039 patients (early surgery in 382 patients). Patients operated early were younger, less frequently female and with higher incidence of unstable angina and hemodynamic instability. Early surgery was found to be an independent predictor for operative mortality only in patients with preoperative creatinine ³ 1.2 mg/dl (OR=2.81; IC 95% 1.03-7.68). No association was found between early surgery and other postoperative outcomes with the exception of greater use of inotropes. Conclusions: isolated coronary artery revascularization may be safely performed within 24 h of coronariography and does not increase operative mortality in patients with normal preoperative levels of creatinine.

Bootstrap testing for cross-correlation under low firing activity.

A new cross-correlation synchrony index for neural activity is proposed. The index is based on the integration of the kernel estimation of the cross-correlation function. It is used to test for the dynamic synchronization levels of spontaneous neural activity under two induced brain states: sleep-like and awake-like. Two bootstrap resampling plans are proposed to approximate the distribution of the test statistics. The results of the first bootstrap method indicate that it is useful to discern significant differences in the synchronization dynamics of brain states characterized by a neural activity with low firing rate. The second bootstrap method is useful to unveil subtle differences in the synchronization levels of the awake-like state, depending on the activation pathway.

Functional two-way analysis of variance and bootstrap methods for neural synchrony analysis.

BACKGROUND: Pairwise association between neurons is a key feature in understanding neural coding. Statistical neuroscience provides tools to estimate and assess these associations. In the mammalian brain, activating ascending pathways arise from neuronal nuclei located at the brainstem and at the basal forebrain that regulate the transition between sleep and awake neuronal firing modes in extensive regions of the cerebral cortex, including the primary visual cortex, where neurons are known to be selective for the orientation of a given stimulus. In this paper, the estimation of neural synchrony as a function of time is studied in data obtained from anesthetized cats. A functional data analysis of variance model is proposed. Bootstrap statistical tests are introduced in this context; they are useful tools for the study of differences in synchrony strength regarding 1) transition between different states (anesthesia and awake), and 2) affinity given by orientation selectivity. RESULTS: An analysis of variance model for functional data is proposed for neural synchrony curves, estimated with a cross-correlation based method. Dependence arising from the experimental setting needs to be accounted for. Bootstrap tests allow the identification of differences between experimental conditions (modes of activity) and between pairs of neurons formed by cells with different affinities given by their preferred orientations. In our test case, interactions between experimental conditions and preferred orientations are not statistically significant. CONCLUSIONS: The results reflect the effect of different experimental conditions, as well as the affinity regarding orientation selectivity in neural synchrony and, therefore, in neural coding. A cross-correlation based method is proposed that works well under low firing activity. Functional data statistical tools produce results that are useful in this context. Dependence is shown to be necessary to account for, and bootstrap tests are an appropriate method with which to do so.

Cross nearest-spike interval based method to measure synchrony dynamics.

A new synchrony index for neural activity is defined in this paper. The method is able to measure synchrony dynamics in low firing rate scenarios. It is based on the computation of the time intervals between nearest spikes of two given spike trains. Generalized additive models are proposed for the synchrony profiles obtained by this method. Two hypothesis tests are proposed to assess for differences in the level of synchronization in a real data example. Bootstrap methods are used to calibrate the distribution of the tests. Also, the expected synchrony due to chance is computed analytically and by simulation to assess for actual synchronization.

Cortical modulation of the transient visual response at thalamic level: a TMS study.

The transient visual response of feline dorsal lateral geniculate nucleus (dLGN) cells was studied under control conditions and during the application of repetitive transcranial magnetic stimulation at 1 Hz (rTMS@1Hz) on the primary visual cortex (V1). The results show that rTMS@1Hz modulates the firing mode of Y cells, inducing an increase in burst spikes and a decrease in tonic firing. On the other hand, rTMS@1Hz modifies the spatiotemporal characteristics of receptive fields of X cells, inducing a delay and a decrease of the peak response, and a change of the surround/center amplitude ratio of RF profiles. These results indicate that V1 controls the activity of the visual thalamus in a different way in the X and Y pathways, and that this feedback control is consistent with functional roles associated with each cell type.

Evaluación de resultados quirúrgicos de la miectomía como tratamiento de la miocardiopatía hipertrófica obstructiva: experiencia de un centro en Uruguay / Evaluation of surgical results of myectomy in the treatment of hypertrophic obstructive cardiomyopathy: experience of a single center in Uruguay

Introducción: la miectomía quirúrgica del septum interventricular es el gold standard en el tratamiento de la miocardiopatía hipertrófica (MH) que requiere cirugía para alivio sintomático. No se encontró publicada ninguna serie de pacientes tratados mediante miectomía en Uruguay, lo que motivó analizar una serie de nuestro centro, valorando variables para su comparación con series de referencia. Material y método: se incluyeron todos los pacientes con miectomía entre enero de 2001 y enero de 2008. Se consignaron variables demográficas, ecocardiográficas y sobrevida a los 18 y 72 meses. Resultados: se incluyeron 23 pacientes, 14 mujeres. Edad promedio 59 años. Siete presentaban familiar de primer grado con MH. Seis presentaban lesiones coronarias significativas. El promedio del gradiente intraventricular máximo fue 96,32 mmHg, SIVD 21,4 mm y FEVI 66%. 17 tenían SAM, y de ellos, 15 presentaban insuficiencia mitral severa. En el preoperatorio, 14 presentaban CF NYHA III y nueve CF IV; 20 recibieron algún procedimiento asociado. La mortalidad operatoria fue de 8,7% (dos pacientes). El gradiente máximo postoperatorio promedio fue 12 mmHg, SIVD 16,65 mm y FEVI 64%. A los 18 meses, 20 estaban vivos y en CF I. La sobrevida actuarial a seis años fue 76,7%. Conclusiones: en 20 de los 23 pacientes se asoció otro procedimiento, mayormente sustitución valvular mitral. La miectomía redujo significativamente los gradientes intraventriculares, el espesor del SIVD y los síntomas en todos los pacientes (p < 0,0001). La mortalidad operatoria fue de 8,7% (dos pacientes) y la sobrevida actuarial a seis años de 76,7%. Estos resultados se equiparan a series de referencia.

Introduction: surgical septum myectomy remains the gold standard for the treatment of obstructive hypertrophic cardiomyopathy requiring surgery forsymptomatic relief. Wasn’t found in the literature, any series of patients underwent myectomy in Uruguay.Our objetive was the analysis of our center series, assessing variables for comparison with reference series.Materials and methods: were included all patients with myectomy from january 2001 to 2008. Demographicsand ultrasonographics variables, and survival at 18 and 72 months were consignated. Results: Were included 23 patients, 14 women. Mean age 59 years. Seven with a first grade relativeaffected of hypertrophic cardiomyopathy (HM). Six with coronary lessions. The mean maximum intraventricular gradient was 96,32 mmHg, dyastolic interventricular septum wide 21,4 mm, EF 66%. 17with systolic anterior motion, 15 with severe mitral insufficience. Before surgery, 14 shows NYHA functionalclass (FC) III, and 9 FCIV. 20 with one additional surgical procedure. Operative mortality was 8,7% (two patients). The mean maximum intraventriculargradient after surgery was 12 mmHg, dyastolic interventricular septum wide 16,65mmand EF 64%. At 18 months, survival was 20 patients, all in FC I. Actuarial survival at 6 years was 76,7%. Conclussions: 20 of 23 patients with an additional procedure, mainly mitral valve substitution. Myectomyimproved intraventricular gradients, DIVS wide and symptoms in all patients (p<0,0001). Operative mortality was 8,7% (two patients), and actuarialsurvival at 6 years was 76,7%. This results are comparable with reference series.

Modulación de la actividad talámica por acetilcolina y óxido nítrico: una llave maestra en el ciclo vigilia-sueño / Acetylcholine and nitric oxide modulation of thalamic activity: a master key in the sleep-wake cycle

El control del ciclo vigilia-sueño depende de la función de grupos neuronales situados en diversas regiones subcorticales. Las rutas ascendentes de activación contactan con el circuito tálamo-córtico-talámico y, de esta manera, tienen una vía muy eficaz de modular la actividad encefálica global. Esto se consigue esencialmente mediante la variación de los niveles de potencial de membrana (Vm) de las neuronas de proyección talámicas, las cuales tienen dos tipos básicos de funcionamiento: un modo tónico y otro en ráfaga. Se han estudiado con cierto detalle las aferencias colinérgicas del tronco encefálico al tálamo visual –núcleo geniculado lateral (NGL) y núcleo perigeniculado (NPG)–, en cuyas sinapsis participan al menos dos sustancias: el neurotransmisor acetilcolina (ACh) y el gas neuromodulador óxido nítrico (NO). Los experimentos de registro extracelular indican que el NO tiene un efecto activador tanto en el NGL como en el NPG, lo cual difiere de los efectos de la ACh, ya que en este caso el efecto sobre el NPG es principalmente inhibidor. En la actualidad se están realizando experimentos de registro intracelular para definir con mayor precisión los efectos sinápticos de ambas sustancias (AU)

Sleep-wake cycle function depends on the activity of neuronal groups located in subcortical regions. Activating systems can effectively modulate global brain activity through their connections with the thalamo-cortico-thalamic network. This is mainly achieved by changing the membrane potential levels of thalamic projection neurons, which possess two modes of spike firing: tonic and bursting. Cholinergic inputs from brainstem to visual thalamus (lateral geniculate (LGN) and perigeniculate (NPG) nucleus) have been extensively studied. In their synapses two substances are of critical importance: the neurotransmitter acetylcholine (ACh) and the gaseous neuromodulator nitric oxide (NO). Intracellular recordings have shown that NO has an activating effect over both LGN and NPG cells; which is different from ACh effects (inhibition over NPG). Ongoing intracellular experiments are trying to delimitate the synaptic effects of both substances (AU)

The operating regime of local computations in primary visual cortex.

In V1, local circuitry depends on the position in the orientation map: close to pinwheel centers, recurrent inputs show variable orientation preferences; within iso-orientation domains, inputs are relatively uniformly tuned. Physiological properties such as cell's membrane potentials, spike outputs, and temporal characteristics change systematically with map location. We investigate in a firing rate and a Hodgkin-Huxley network model what constraints these tuning characteristics of V1 neurons impose on the cortical operating regime. Systematically varying the strength of both recurrent excitation and inhibition, we test a wide range of model classes and find the likely models to account for the experimental observations. We show that recent intracellular and extracellular recordings from cat V1 provide the strongest evidence for a regime where excitatory and inhibitory recurrent inputs are balanced and dominate the feed-forward input. Our results are robust against changes in model assumptions such as spatial extent and strength of lateral inhibition. Intriguingly, the most likely recurrent regime is in a region of parameter space where small changes have large effects on the network dynamics, and it is close to a regime of "runaway excitation," where the network shows strong self-sustained activity. This could make the cortical response particularly sensitive to modulation.

Cirugía cardíaca en octogenarios. Comparación de los resultados a corto y mediano plazo con la población menor a 80 años / Cardiac surgery in octogenarians. Compararison of results from short to medium term with population younger than 80 years

Objetivo: evaluar resultados a corto y mediano plazo de cirugía cardíaca en octogenarios. Material y método: se incluyeron los pacientes operados entre el 1 de enero de 2000 hasta el 31 de diciembre de 2005 (n=5.450), en forma prospectiva. Se analizaron: variables hemodinámicas, factores de riesgo preoperatorio, evolución post operatoria. Se seleccionaron dos poblaciones: menores de 80 años (G1) y de 80 años o más (G2). El análisis estadístico se realizó a través del test de “t”, test de Mann-Whitney, chi cuadrado, método de Kaplan-Meier, log-rank test y el modelo de regresión logística. Resultados: se operaron 217 pacientes mayores de 80 años (3,98%), media 82,2 años (rango: 80-90). Sin diferencias para las variables: enfermedad pulmonar obstructiva crónica (EPOC), enfermedad vascularperiférica, cerebral, hipertensión arterial (HTA), cirugía cardíaca previa, inestabilidad hemodinámica, fracción de eyección del ventrículo izquierdo (FEVI), infarto agudo de miocardio (IAM) previo. Hubo diferencias entre G1 y G2 en: diabetes (24,8% versus 14,3%; p<0,0001), tabaquismo (23,2% versus 5,1%; p<0,0001), sexo femenino (33% versus 45,6%; p<0,001), filtrado glomerular estimado (75,5 ml/min versus 46,6 ml/min; p<0,0001), cirugía coronaria aislada (63,7% versus 43,3%; p<0,0001), cambio de válvula aórtica (25,2% versus 52,5%; p<0,0001), EuroSCORE (5,7± 2,8 versus 9,1±1,9; p<0,001). La mortalidad operatoria fue 6,3% versus 9,7% (p<0,05), la mortalidad esperada por EuroSCORE fue 6,8% versus 14,9% (p<0,05)...

Purpose: To evaluate short and mid-term results of cardiac surgery in octogenarians. Methods: All patients operated on between 1/1/200 and 31/12 2005 (n=5.450) were prospectively included. Hemodinamic parameters, preoperative risk factors, and postoperative evolution were analysed. Patients were separated in 2 groups: < 80 years old (G1), ³ 80 years old (G2). Statistical analysis was performed with “t” test, Mann-Whitney test, Chi square test, Kaplan-Meier method, log-rank test and logistic regresion model. Results: Surgery was performed on 217 patients = 80 años (3,98%), average 82,2 years (rank: 80-90). No differences were found in: COPD, periferial vascular disease; cerebro-vascular disease, high blood pressure, previous cardiac surgery, hemodinamic inestability, LVEF, previous AMI. There were differences between G1 and G2 in: diabetes (24,8% versus 14,3%; p<0,0001), smoking (23,2% versus 5,1%; p<0,0001), females (33% versus 45,6%; p<0,001), estimated glomerular filtration (75,5% versus 46,6 ml/min; p<0,0001), coronary surgery alone (63,7% versus 43,3%; p<0,0001), aortic valve replacement (25,2% versus 52,5%; p<0,0001), EuroSCORE (5,7± 2,8 versus 9,1± 1,9; p<0,001). The operative mortality (OM) was 6,3% versus 9,7% (p<0,05), estimated mortality with EuroSCORE was 6,8 vs 14,9% (p<0,05). Patiets in G2 had longer length of stay (LOS), globally and in ICU, longer ventilatory mechanical support and reintervention for bleeding. Patients in both groups had similar incidence of stroke, perioperative AMI and 5 years mortality (21,3% versus 17,3%; p=NS). Conclusions: Cardiac surgery is a reasonable option in selected octogenarians, with greater operative mortality and hospital stay. Long run prognosis is similar in both groups.

Changes in visual responses in the feline dLGN: selective thalamic suppression induced by transcranial magnetic stimulation of V1.

Transcranial magnetic stimulation (TMS) of the cortex can modify activity noninvasively and produce either excitatory or inhibitory effects, depending on stimulus parameters. Here we demonstrate controlled inhibitory effects on the large corticogeniculate feedback pathway from primary visual cortex to cells of the dorsal lateral geniculate nucleus (dLGN) that are focal and reversible-induced by either single pulses or trains of pulses of TMS. These effects selectively suppress the sustained component of responses to flashed spots or moving grating stimuli and are the result of loss of spikes fired in tonic mode, whereas the number of spikes fired in bursts remain the same. We conclude that acute inactivation of the corticogeniculate downflow selectively affects the tonic mode. We found no evidence to suggest that cortical inactivation increased burst frequency.

Cortical modulation of dorsal column nuclei: a computational study.

We present a computational study aimed at exploring the sensorimotor cortex modulation of the behaviour of dorsal column nuclei, specifically the impact of synaptic parameters, during both sleep and waking conditions. On the basis of the circuit proposed by Canedo et al. (2000), we have developed realistic computational models that have been tested with simultaneous electrocorticographic as well as intracellular cuneate recordings performed in anaesthetized cats. The results show that, (1) under sleep conditions, the model can block the transmission of afferent sensory information and, (2) operations expected during wakefulness, such as filtering and facilitation, can be performed if synaptic parameters are appropriately tuned.

Invariant computations in local cortical networks with balanced excitation and inhibition.

Cortical computations critically involve local neuronal circuits. The computations are often invariant across a cortical area yet are carried out by networks that can vary widely within an area according to its functional architecture. Here we demonstrate a mechanism by which orientation selectivity is computed invariantly in cat primary visual cortex across an orientation preference map that provides a wide diversity of local circuits. Visually evoked excitatory and inhibitory synaptic conductances are balanced exquisitely in cortical neurons and thus keep the spike response sharply tuned at all map locations. This functional balance derives from spatially isotropic local connectivity of both excitatory and inhibitory cells. Modeling results demonstrate that such covariation is a signature of recurrent rather than purely feed-forward processing and that the observed isotropic local circuit is sufficient to generate invariant spike tuning.

Local networks in visual cortex and their influence on neuronal responses and dynamics.

Networks of neurons in the cerebral cortex generate complex outputs that are not simply predicted by their inputs. These emergent responses underlie the function of the cortex. Understanding how cortical networks carry out such transformations requires a description of the responses of individual neurons and of their networks at multiple levels of analysis. We focus on orientation selectivity in primary visual cortex as a model system to understand cortical network computations. Recent experiments in our laboratory and others provide significant insight into how cortical networks generate and maintain orientation selectivity. We first review evidence for the diversity of orientation tuning characteristics in visual cortex. We then describe experiments that combine optical imaging of orientation maps with intracellular and extracellular recordings from individual neurons at known locations in the orientation map. The data indicate that excitatory and inhibitory synaptic inputs are summed across the cortex in a manner that is consistent with simple rules of integration of local inputs. These rules arise from known anatomical projection patterns in visual cortex. We propose that the generation and plasticity of orientation tuning is strongly influenced by local cortical networks-the diversity of these properties arises in part from the diversity of neighbourhood features that derive from the orientation map.

A computational model of cuneothalamic projection neurons.

The dorsal column nuclei, cuneatus and gracilis, play a fundamental role in the processing and integration of somesthetic ascending information. Intracellular and patch-clamp recordings obtained in cat in vivo have shown that cuneothalamic projection neurons present two modes of activity: oscillatory and tonic (Canedo et al 1998 Neuroscience 84 603-17). The former is the basis of generating, in sleep and anaesthetized states, slow, delta and spindle rhythms under the control of the cerebral cortex (Mariño et al 2000 Neuroscience 95 657-73). The latter is needed, during wakefulness, to process somesthetic information in real time. To study this behaviour we have developed the first realistic computational model of the cuneothalamic projection neurons. The modelling was guided by experimental recordings, which suggest the existence of hyperpolarization-activated inward currents, transient low- and high-threshold calcium currents, and calcium-activated potassium currents. The neuronal responses were simulated during (1) sleep, (2) transition from sleep to wakefulness and (3) wakefulness under both excitatory and inhibitory synaptic input. In wakefulness the model predicts a set of synaptically driven firing modes that could be associated with information processing strategies in the middle cuneate nucleus.

Nitric oxide-mediated cortical activation: a diffuse wake-up system.

Nitric oxide (NO) has been implicated in some of the central pathways engaged in the regulation of the sleep-wake cycle. The existence of nitric oxide synthase (NOS) in the cholinergic basal forebrain (BF) cells projecting to the cortex suggests a role for NO in the activation induced by the BF during arousal. We tested, in the anesthetized cat, the hypothesis that inhibition of NOS would decrease the ability of BF cholinergic fibers to induce cortical activation. In control conditions, BF stimulation evoked an awake-like EEG pattern (i.e., a decrease in the low-frequency-high-amplitude oscillatory activity and an increase in the high-frequency-low-amplitude activity). After blocking NOS activity, the capacity of BF stimulation to induce cortical activation was strongly impaired. Furthermore, voltammetric measurements of NO levels revealed an increase in cortical NO after BF stimulation, also blocked by systemic NOS inhibition. These results indicate that the blockade of NOS activity significantly reduces the ability of BF stimulation to induce changes in the EEG pattern and suggest a role for NO in the BF-cholinergic system implicated in arousal mechanisms.

Synaptic integration by V1 neurons depends on location within the orientation map.

Neurons in the primary visual cortex (V1) are organized into an orientation map consisting of orientation domains arranged radially around "pinwheel centers" at which the representations of all orientations converge. We have combined optical imaging of intrinsic signals with intracellular recordings to estimate the subthreshold inputs and spike outputs of neurons located near pinwheel centers or in orientation domains. We find that neurons near pinwheel centers have subthreshold responses to all stimulus orientations but spike responses to only a narrow range of orientations. Across the map, the selectivity of inputs covaries with the selectivity of orientations in the local cortical network, while the selectivity of spike outputs does not. Thus, the input-output transformation performed by V1 neurons is powerfully influenced by the local structure of the orientation map.

Sensorimotor Integration at the Dorsal Column Nuclei.

Interaction among primary afferents, corticofugal fibers, and intrinsic elements allows for sensorimotor integration at the dorsal column nuclei. The interneurons permit the spatial localization, the recurrent collaterals synchronize the activity of projecting cells with overlapping receptive fields, and the corticofugal fibers induce a central zone of activity surrounded by a peripheral zone of inhibition.