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Fast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity of different GABAergic interneurons in prefrontal cortex under conditions mimicking distinct brain states. While fast-spiking neurons always exhibited a wide bandwidth of around 400 Hz, the response properties of spike-frequency adapting interneurons switched with the background input's statistics. Slowly fluctuating background activity, as typical for sleep or quiet wakefulness, dramatically boosted the neurons' sensitivity to gamma and ripple frequencies. We developed a time-resolved dynamic gain analysis and revealed rapid sensitivity modulations that enable neurons to periodically boost gamma oscillations and ripples during specific phases of ongoing low-frequency oscillations. This mechanism predicts these prefrontal interneurons to be exquisitely sensitive to high-frequency ripples, especially during brain states characterized by slow rhythms, and to contribute substantially to theta-gamma cross-frequency coupling.

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Streams of action potentials or long depolarizations evoke a massive exocytosis of transmitters and peptides from the surface of dendrites, axons and cell bodies of different neuron types. Such mode of exocytosis is known as extrasynaptic for occurring without utilization of synaptic structures. Most transmitters and all peptides can be released extrasynaptically. Neurons may discharge their contents with relative independence from the axon, soma and dendrites. Extrasynaptic exocytosis takes fractions of a second in varicosities or minutes in the soma or dendrites, but its effects last from seconds to hours. Unlike synaptic exocytosis, which is well localized, extrasynaptic exocytosis is diffuse and affects neuronal circuits, glia and blood vessels. Molecules that are liberated may reach extrasynaptic receptors microns away. The coupling between excitation and exocytosis follows a multistep mechanism, different from that at synapses, but similar to that for the release of hormones. The steps from excitation to exocytosis have been studied step by step for the vital transmitter serotonin in leech Retzius neurons. The events leading to serotonin exocytosis occur similarly for the release of other transmitters and peptides in central and peripheral neurons. Extrasynaptic exocytosis occurs commonly onto glial cells, which react by releasing the same or other transmitters. In the last section, we discuss how illumination of the retina evokes extrasynaptic release of dopamine and ATP. Dopamine contributes to light-adaptation; ATP activates glia, which mediates an increase in blood flow and oxygenation. A proper understanding of the workings of the nervous system requires the understanding of extrasynaptic communication.

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Short-term plasticity gates information transfer across neuronal synapses and is thought to be involved in fundamental brain processes, such as cortical gain control and sensory adaptation. Neurons employ synaptic vesicle priming proteins of the CAPS and Munc13 families to shape short-term plasticity in vitro, but the relevance of this phenomenon for information processing in the intact brain is unknown. By combining sensory stimulation with in vivo patch-clamp recordings in anesthetized mice, we show that genetic deletion of CAPS-1 in thalamic neurons results in more rapid adaptation of sensory-evoked subthreshold responses in layer 4 neurons of the primary visual cortex. Optogenetic experiments in acute brain slices further reveal that the enhanced adaptation is caused by more pronounced short-term synaptic depression. Our data indicate that neurons engage CAPS-family priming proteins to shape short-term plasticity for optimal sensory information transfer between thalamic and cortical neurons in the intact brain in vivo.

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Zoom Image Abstract Introduction Penile carcinoma is an aggressive disease with catastrophic consequences that frequently lead to death. Therefore, further knowledge on the prognostic factors that can help identify patients in need of more aggressive treatments becomes essential. Objective To identify the prognostic factors for lymph node (LN) involvement and tumor recurrence in patients diagnosed with squamous cell carcinoma of the penis (SCCP). Methods A retrospective cohort study was conducted. Patients diagnosed and treated for SCCP at Instituto Nacional de Cancerología between 2008 and 2015 were included in the sample. Cases in which no information on recurrence was available for the follow-up were excluded, as well as patients with no initial pathology and those getting penile reconstructions after cancer. Relevant data was retrieved from the medical records of each patient, and a descriptive analysis was performed. Subsequently, this data was used to apply a logistic regression model to determine the potential clinical and histopathological prognostic factors. Results A total of 104 patients were included in the present study. The average age of the sample was 59 years, while the follow-up averaged 24 months per patient. Inguinal lymphadenectomy was performed on 61 patients (59%) during the follow-up. The logistic regression model showed that lymphovascular invasion (odds ratio [OR]: 6.7; 95% confidence interval [95%CI]: 1.2­35) and poor tumor differentiation (OR: 17; 95%CI: 3.2­92) were associated with tumor recurrence. Likewise, the lymphadenectomy procedures showed that lymphovascular invasion was associated with LN involvement (OR: 3.3; 95%CI: 1.1­10). Conclusion Lymphovascular invasion was the strongest prognostic factor observed in our sample, aiding in the prediction of inguinal LN involvement and tumor recurrence in SCCP patients

Introduccion El cáncer de pene es una enfermedad agresiva con consecuencias catastróficas que frecuentemente llevan a la muerte. Por lo tanto, es esencial un mayor conocimiento sobre los factores pronósticos que pueden ayudar a identificar a los pacientes que necesitan tratamientos más agresivos. Objetivo Identificar los factores pronósticos patológicos de compromiso ganglionar inguinal y recaída tumoral en pacientes con carcinoma escamocelular de pene. Métodos Se realizó un estudio de cohorte retrospectivo. Se incluyeron en la muestra pacientes diagnosticados y tratados por carcinoma escamocelular de pene (SCCP) en el Instituto Nacional de Cancerología entre 2008 y 2015. Los casos en los que no había información sobre la recurrencia en el seguimiento fueron excluidos, así como los pacientes sin patología inicial y aquellos que reciben reconstrucciones del pene después del cáncer. Se recuperaron los datos relevantes de los registros médicos de cada paciente, y una descripción fue realizada. Posteriormente, estos datos se utilizaron para aplicar un modelo de regresión logística para determinar los posibles factores pronósticos clínicos e histopatológicos. Resultados Un total de 104 pacientes fueron incluidos en el estudio. La edad promedio de la muestra fue de 59 años, mientras que el seguimiento promedió fue de 24 meses por paciente. La linfadenectomía inguinal se realizó en 61 pacientes (59%) durante el seguimiento. El modelo de regresión logística mostró que la invasión linfovascular (odds ratio [OR]: 6,7; intervalo de confianza del 95% [IC 95%]: 1,2­35) y la pobre diferenciación tumoral (OR: 17; IC 95%: 3,2­92) se asociaron con recurrencia tumoral. Así mismo, los procedimientos de linfadenectomía mostraron que la invasión linfovascular se asoció con afectación de LN. (OR: 3,3; IC 95%: 1,1-10). Conclusión La invasión linfovascular es el factor pronóstico independiente más importante que se asocia de manera independiente con compromiso ganglionar inguinal positivo y recaída tumoral.

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Resumen Objetivo: Determinar la efectividad del uso de las tecnologías de la información y la comunicación, en la adherencia al tratamiento de los pacientes con insuficiencia cardiaca, que asistieron a una Unidad de Insuficiencia Cardiaca de Bogotá. Métodos: Se realizó un ensayo clínico con preprueba, posprueba y grupo de control. Se conformaron aleatoriamente tres grupos de 37 participantes cada uno, a dos de los cuales se les aplicó una intervención durante dos meses basada en el uso de las tecnologías de la información y la comunicación; el grupo 1 recibió seguimiento telefónico más envío de mensajes de texto, el grupo 2 seguimiento telefónico más envío de correos electrónicos y el grupo 3 correspondiente al grupo de control recibió la intervención de enfermería usual en una Unidad de Insuficiencia Cardiaca. Resultados: Los tres grupos definidos para el estudio modificaron significativamente sus niveles medios de adherencia; en los grupos 1 y 2 dicho incremento es atribuible a la intervención con el uso de las tecnologías de la información y la comunicación, de igual manera la adherencia en los participantes del grupo control que recibieron la atención usual en una Unidad de Insuficiencia Cardiaca, también muestra un incremento significativo. Conclusiones: El uso de las tecnologías de la información y la comunicación: el seguimiento telefónico asociado a los mensajes de texto y los correos electrónicos incrementó la adherencia al tratamiento farmacológico y no farmacológico en pacientes con insuficiencia cardiaca a través de la motivación y el seguimiento de los pacientes.

Abstract Motivation: To determine the efficacy of the use of information and communication technologies in the treatment adherence of patients with heart failure that were assisted at the Heart Failure Unit of Bogotá. Methods: A clinical trial was conducted with pre-, post-test and control group. Three randomised groups of 37 participants each were conformed, two of which received an intervention during two months based in the use of information and communication technology; group 1 received telephone follow-up plus text messages, group 2 telephone follow-up plus emails and group 3, which was the control group, received the usual nurse follow-up at a Heart Failure Unit. Results: The three defined study groups significantly modified their average adherence levels; groups 1 and 2 the increase is attributable to the intervention with the use of information and communication technologies, likewise, adherence of the control group participants who received the usual care at a Heart Failure Unit also showed a significant increase. Conclusion: The use of information and communication technologies, such as the telephone follow-up associated to text messages and emails, rose the adherence to the pharmacological and non-pharmacological treatment in patients with heart failure by motivating and monitoring patients.

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Serotonin, a modulator of multiple functions in the nervous system, is released predominantly extrasynaptically from neuronal cell bodies, axons and dendrites. This paper describes how serotonin is released from cell bodies of Retzius neurons in the central nervous system (CNS) of the leech, and how it affects neighbouring glia and neurons. The large Retzius neurons contain serotonin packed in electrodense vesicles. Electrical stimulation with 10 impulses at 1 Hz fails to evoke exocytosis from the cell body, but the same number of impulses at 20 Hz promotes exocytosis via a multistep process. Calcium entry into the neuron triggers calcium-induced calcium release, which activates the transport of vesicle clusters to the plasma membrane. Exocytosis occurs there for several minutes. Serotonin that has been released activates autoreceptors that induce an inositol trisphosphate-dependent calcium increase, which produces further exocytosis. This positive feedback loop subsides when the last vesicles in the cluster fuse and calcium returns to basal levels. Serotonin released from the cell body is taken up by glia and released elsewhere in the CNS. Synchronous bursts of neuronal electrical activity appear minutes later and continue for hours. In this way, a brief train of impulses is translated into a long-term modulation in the nervous system.

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Propósito: La presente investigación tuvo como objeto determinar la efectividad del uso de tecnologías de la información y la comunicación, en la adherencia al tratamiento de los pacientes con insuficiencia cardiaca, que asisten a la Unidad de Insuficiencia Cardiaca de la Clínica Universitaria Colombia. Metodología: Se realizó un ensayo clínico con pre prueba, pos prueba y grupo control. Se conformaron aleatoriamente tres grupos de participantes cada uno, a dos de los cuales se les aplicó una intervención durante dos meses basada en el uso de Tecnologías de la Información y la Comunicación: el grupo 1 recibió seguimiento telefónico más envío de mensajes de texto, el grupo 2 seguimiento telefónico más envío de correos electrónicos; y el grupo 3 correspondiente al grupo control recibió la intervención de enfermería usual en la Unidad de Insuficiencia Cardiaca. Resultados: El uso de las tecnologías de la información y la comunicación C en pacientes con insuficiencia cardiaca incremento la adherencia al tratamiento farmacológico y no farmacológico, frente al grupo control que recibió la intervención de enfermería usual en la Unidad de Insuficiencia Cardiaca.

Purpose: The present study was to determine the effectiveness of using information and communications technology, adherence to treatment of patients with heart failure, attending the Heart Failure Unit at the University Hospital Colombia. Methodology: A clinical trial was conducted with pre test, post test and control group. They were formed randomly three groups of participants each, two of which were given an intervention for two months based on the use of information and communications technology: group 1 received telephone follow more sending text messages, the Group 2 telephone follow more sending emails; and group 3 for the control group received usual nursing intervention in Heart Failure Unit. Results: The use of information and communications technology in patients with heart failure increased adherence to pharmacological and non-pharmacological treatment, compared to the control group that received usual nursing intervention in Heart Failure Unit.

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The soma of many neurons releases large amounts of transmitter molecules through an exocytosis process that continues for hundreds of seconds after the end of the triggering stimulus. Transmitters released in this way modulate the activity of neurons, glia and blood vessels over vast volumes of the nervous system. Here we studied how somatic exocytosis is maintained for such long periods in the absence of electrical stimulation and transmembrane Ca(2+) entry. Somatic exocytosis of serotonin from dense core vesicles could be triggered by a train of 10 action potentials at 20 Hz in Retzius neurons of the leech. However, the same number of action potentials produced at 1 Hz failed to evoke any exocytosis. The 20-Hz train evoked exocytosis through a sequence of intracellular Ca(2+) transients, with each transient having a different origin, timing and intracellular distribution. Upon electrical stimulation, transmembrane Ca(2+) entry through L-type channels activated Ca(2+)-induced Ca(2+) release. A resulting fast Ca(2+) transient evoked an early exocytosis of serotonin from sparse vesicles resting close to the plasma membrane. This Ca(2+) transient also triggered the transport of distant clusters of vesicles toward the plasma membrane. Upon exocytosis, the released serotonin activated autoreceptors coupled to phospholipase C, which in turn produced an intracellular Ca(2+) increase in the submembrane shell. This localized Ca(2+) increase evoked new exocytosis as the vesicles in the clusters arrived gradually at the plasma membrane. In this way, the extracellular serotonin elevated the intracellular Ca(2+) and this Ca(2+) evoked more exocytosis. The resulting positive feedback loop maintained exocytosis for the following hundreds of seconds until the last vesicles in the clusters fused. Since somatic exocytosis displays similar kinetics in neurons releasing different types of transmitters, the data presented here contributes to understand the cellular basis of paracrine neurotransmission.

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Cnidarians comprise a taxon with a high biodiversity of cytolitic, neurotoxic and cardiotoxic compounds, which have not been studied on insulin release. We tested the effect of a crude extract of Zoanthus sociatus (Ellis, 1767) and the low molecular weight fraction of this extract on insulin secretion in isolated rat ß-cells and also in a glucose tolerance test in vivo. We observed that the extract inhibited insulin release by reducing the amount secreted by individual ß-cells and also by silencing a fraction of the secreting population. This effect coincided with a diminished rise of intracellular Ca(+2) in response to high glucose and high K+ -induced depolarization. Moreover intraperitoneal administration of the low molecular weight fraction produced glucose intolerance in adult rats. The active fraction exhibited molecular weights similar to the neurotoxins described in the phylum. Our results broaden the toxic effects of cnidarian venoms and show evidence of potential modulators of voltage-gated Ca(+2) channels in this group.

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