Local Field Potentials: Myths and Misunderstandings

The intracerebral local field potential (LFP) is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a composite signal that receives contributions from multiple neural sources, yet interpreting its nature and significance may be hindered by several confounding factors and technical limitations. By and large, the main factor defining the amplitude of LFPs is the geometry of the current sources, over and above the degree of synchronization or the properties of the media. As such, similar levels of activity may result in potentials that differ in several orders of magnitude in different populations. The geometry of these sources has been experimentally inaccessible until intracerebral high density recordings enabled the co-activating sources to be revealed. Without this information, it has proven difficult to interpret a century's worth of recordings that used temporal cues alone, such as event or spike related potentials and frequency bands. Meanwhile, a collection of biophysically ill-founded concepts have been considered legitimate, which can now be corrected in the light of recent advances. The relationship of LFPs to their sources is often counterintuitive. For instance, most LFP activity is not local but remote, it may be larger further from rather than close to the source, the polarity does not define its excitatory or inhibitory nature, and the amplitude may increase when source's activity is reduced. As technological developments foster the use of LFPs, the time is now ripe to raise awareness of the need to take into account spatial aspects of these signals and of the errors derived from neglecting to do so.This work was supported by the Spanish Ministry of Economy and Competitiveness (BFU2013-41533R).Peer reviewedPeer Reviewe

Parallel readout of pathway-specific inputs to laminated brain structures

Local field potentials (LFPs) capture the electrical activity produced by principal cells during integration of converging synaptic inputs from multiple neuronal populations. However, since synaptic currents mix in the extracellular volume, LFPs have complex spatiotempo-ral structure, making them hard to exploit. Here we propose a biophysical framework to identify and separate LFP-generators. First we use a computational multineuronal model that scales up single cell electrogenesis driven by several synaptic inputs to realistic aggregate LFPs. This approach relies on the fixed but distinct locations of synaptic inputs from different presynaptic populations targeting a laminated brain structure. Thus the LFPs are contributed by several pathway-specific LFP-generators, whose electrical activity is defined by the spatial distribution of synaptic terminals and the time course of synaptic currents initiated in target cells by the corresponding presynaptic population. Then we explore the efficacy of independent component analysis to blindly separate converging sources and reconstruct pathway-specific LFP-generators. This approach can optimally locate synaptic inputs with subcellular accuracy while the reconstructed time course of pathway-specific LFP-generators is reliable in the millisecond scale. We also describe few cases where the non-linear intracellular interaction of strongly overlapping LFP-generators may lead to a significant cross-contamination and the appearance of derivative generators. We show that the approach reliably disentangle ongoing LFPs in the hippocampus into contribution of several LFP-generators.We were able to readout in parallel the pathway-specific presynap-tic activity of projection cells in the entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3. Thus we provide formal mathematical and experimental support for parallel readout of the activity of converging presynaptic populations in working neuronal circuits from common LFPs. © 2011 Makarova, Ibarz, Makarov, Benito and Herreras.This study has been financed by grants FIS2010-20054 and BFU2010-19192 of the Spanish Ministry of Science and Innovation.Peer Reviewe

Centro deportivo de alta montaña y esquí en Candanchú

El presente proyecto se realiza como encargo de la Universidad de Zaragoza del estudio y desarrollo de un Centro Deportivo de alta montaña y esquí en Candanchú.La estación se ubica en el Pirineo oscense, cuna del esquí español, perteneciente al término municipal de Aisa en Huesca. La estación de esquí de Candanchú abrió en 1928, surgió a raíz del turismo por los deportes de montaña, produciéndose un aumento en la edificación alrededor de manera drástica y desordenada, creando un territorio sin carácter más que el individual de los propios edificios.La propuesta pretende solventar la absoluta desconexión espacial y estética, creado un lugar de transición entre los dos edificios colindantes y con la suficiente fuerza para formar un foco en Candanchú, estableciendo así un punto de referencia y dando origen a un orden urbano.<br /

Slow-wave activity in the S1HL cortex is contributed by different layer-specific field potential sources during development

Spontaneous correlated activity in cortical columns is criticalfor postnatal circuit refinement.We used spatial discriminationtechniques to explore the late maturation of synaptic pathways through the laminar distribution of the field potential (FP) generators underlying spontaneous and evoked activities ofthe S1HL cortex in juvenile (P14 –P16) and adult anesthetized rats. Juveniles exhibit an intermittent FP pattern resembling Up/Down states in adults, but with much reduced power and different laminar distribution. Whereas FPs in active periods are dominated by a layer VI generator in juveniles, in adults a developing multipart generatortakes over, displaying current sinks in middle layers (III–V). The blockade of excitatory transmission in upper and middle layers of adults recovered the juvenile-like FP profiles. In additiontothe layer VI generator, a gamma-specific generator in supragranular layers wasthe same in both age groups.While searching for dynamical coupling among generators in juveniles we found significant cross-correlation in one-half of the tested pairs, whereas excessive coherence hindered their efficient separation in adults. Also, potentials evoked by tactile and electrical stimuli showed different short-latency dipoles between the two age groups, and the juveniles lacked the characteristic long latency UP state currents in middle layers. In addition, the mean firing rate of neurons was lower in juveniles. Thus, cortical FPs originate from different intracolumnar segments as they become active postnatally. We suggest that although some cortical segments are active early postnatally, a functional sensory-motor control relies on a delayed maturation and network integration of synaptic connections in middle layers

Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization

Background: Within 2 min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30 years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s Methods: Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued. Results: Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast, SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury. Conclusions: Spreading depolarizations better account for the acute neuronal injury arising from brain ischemia than does the early and excessive release of glutamate.Grants to RDA from the Canadian Heart & Stroke Foundation, National Science Engineering and Research Council and the New Frontiers in Research Fund, to E.F from the National Research, Development and Innovation Office of Hungary, grant no. K134377; and the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593, and to JPD from the DFG (German research Council) (DFG DR323/5-1,DFG DR 323/10-1) BMBF Bundesministerium fuer Bildung und Forschung (Era-Net Neuron EBio2, with funds from BMBF 01EW2004)

Diseño metodológico para el desarrollo de benchmarks para robots cuadrúpedos de monitorización agro-ecológica

El cabio climático y la contaminación amenazan una de cada ocho especies que habitan en bosques y océanos. Para atajar este problema la Unión Europea ha planificado una serie de cambios a todos los niveles de la sociedad europea que quedan recogidos en el Pacto Verde Europeo. Entre las numerosas políticas que contempla este plan, se encuentran las destinadas a preservar y restaurar los ecosistemas dentro de las fronteras europeas, entre los que se encuentran los protegidos por la Red Natura 2000. La Red Natura 2000 es una red ecológica para la protección de áreas con alta biodiversidad marina y terrestre encargada de conservar los diferentes entornos naturales dentro de Europa. Aun siendo la mayor red del mundo, solo es capaz de monitorizar el 18% de las áreas naturales terrestres y el 6% de las marinas. La tarea de monitorización, es decir, la evaluación periódica y repetible de un conjunto dado de indicadores clave, es un instrumento esencial para estudiar los sistemas ambientales. Dicha monitorización de los hábitats naturales tiene tres funciones principales: (1) proporcionar información sobre las diferencias del estado actual del medio ambiente en comparación con un estado de referencia. (2) conocer los efectos de las acciones encaminadas a conservar el estado del medio ambiente. (3) evaluar los efectos de las perturbaciones en los medios naturales.(Yoccoz, 2012). Dentro del Pacto Verde se pretende aumentar la superficie monitorizada hasta el 30% en el año 2030 (Estrategia de biodiversidad, EU 2030). Para alcanzar esta cifra, los programas de monitorización dependen de la capacidad de operarios humanos que tengan los conocimientos necesarios, así como la capacidad para desplazarse por entornos complicados. A pesar de que las tareas de monitorización requieren de técnicas repetitivas, consistentes y económicas, actualmente los operarios especializados trabajan sin asistencia robotizada, que podría ayudar enormemente con tareas tan complicadas. Este trabajo se centra en la monitorización de áreas rurales, tanto naturales como cultivadas, mediante el uso de pruebas de evaluación estandarizadas (benchmarking). Gracias a dichas pruebas se podrá asegurar una plataforma europea con capacidad para comparar diversos robots con capacidad de desplazarse por entornos naturales bajo las mismas métricas

Determining the True Polarity and Amplitude of Synaptic Currents Underlying Gamma Oscillations of Local Field Potentials

Fluctuations in successive waves of oscillatory local field potentials (LFPs) reflect the ongoing processing of neuron populations. However, their amplitude, polarity and synaptic origin are uncertain due to the blending of electric fields produced by multiple converging inputs, and the lack of a baseline in standard AC-coupled recordings. Consequently, the estimation of underlying currents by laminar analysis yields spurious sequences of inward and outward currents. We devised a combined analytical/experimental approach that is suitable to study laminated structures. The approach was essayed on an experimental oscillatory LFP as the Schaffer-CA1 gamma input in anesthetized rats, and it was verified by parallel processing of model LFPs obtained through a realistic CA1 aggregate of compartmental units. This approach requires laminar LFP recordings and the isolation of the oscillatory input from other converging pathways, which was achieved through an independent component analysis. It also allows the spatial and temporal components of pathway-specific LFPs to be separated. While reconstructed Schaffer-specific LFPs still show spurious inward/outward current sequences, these were clearly stratified into distinct subcellular domains. These spatial bands guided the localized delivery of neurotransmitter blockers in experiments. As expected, only Glutamate but not GABA blockers abolished Schaffer LFPs when applied to the active but not passive subcellular domains of pyramidal cells. The known chemical nature of the oscillatory LFP allowed an empirical offset of the temporal component of Schaffer LFPs, such that following reconstruction they yield only sinks or sources at the appropriate sites. In terms of number and polarity, some waves increased and others decreased proportional to the concomitant inputs in native multisynaptic LFPs. Interestingly, the processing also retrieved the initiation time for each wave, which can be used to discriminate afferent from postsynaptic cells in standard spike-phase correlations. The applicability of this approach to other pathways and structures is discussed. © 2013 Martín-Vázquez et al.Peer Reviewe

PyramidalExplorer: A New Interactive Tool to Explore Morpho-Functional Relations of Human Pyramidal Neurons

This work presents PyramidalExplorer, a new tool to interactively explore and reveal the detailed organization of the microanatomy of pyramidal neurons with functionally related models. It consists of a set of functionalities that allow possible regional differences in the pyramidal cell architecture to be interactively discovered by combining quantitative morphological information about the structure of the cell with implemented functional models. The key contribution of this tool is the morpho-functional oriented design that allows the user to navigate within the 3D dataset, filter and perform Content-Based Retrieval operations. As a case study, we present a human pyramidal neuron with over 9000 dendritic spines in its apical and basal dendritic trees. Using PyramidalExplorer, we were able to find unexpected differential morphological attributes of dendritic spines in particular compartments of the neuron, revealing new aspects of the morpho-functional organization of the pyramidal neuron.This work has been partially supported by the Spanish Ministry of Economy and Competitiveness (Grants TIN2014-57481 and BFU2013-41533R, and the Cajal Blue Brain Project C080020-09, the Spanish partner of the Blue Brain initiative from EPFL), by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 604102 (Human Brain Project) and by a grant from the Alzheimer’s Association (ZEN-15-321663). RB-P was supported by the Ministerio de Economia y Competitividad (CSIC).Peer reviewedPeer Reviewe

Relation of apical dendritic spikes to output decision in CA1 pyramidal cells during synchronous activation: A computational study

Recent studies on the initiation and propagation of dendritic spikes have modified the classical view of postsynaptic integration. Earlier we reported that subthreshold currents and spikes recruited by synaptic currents play a critical role in defining outputs following synchronous activation. Experimental factors strongly condition these currents due to their nonlinear behaviour. Hence, we have performed a detailed parametric study in a CA1 pyramidal cell model to explore how different variables interact and initiate dendritic spiking, and how they influence cell output. The input pattern, the relative excitability of axon and dendrites, the presence/modulation of voltage-dependent channels, and inhibition were cross analysed. Subthreshold currents and spikes on synaptically excited branches fired spikes in other branches to jointly produce different modalities of apical shaft spiking with a variable impact on cell output. Synchronous activation initiated a varying number and temporal scatter of firing branches that produced in the apical shaft-soma axis nonpropagating spikes, pseudosaltatory or continuous forward conduction, or backpropagation. As few as 6-10 local spikes within a time window of 2 ms ensure cell output. However, the activation mode varied extremely when two or more variables were cross-analysed, becoming rather unpredictable when all the variables were considered. Spatially clustered inputs and upper modulation of dendritic Na+ or Ca2+ electrogenesis favour apical decision. In contrast, inhibition biased the output decision toward the axon and switched between dendritic firing modes. We propose that dendrites can discriminate input patterns and decide immediate cell output depending on the particular state of a variety of endogenous parameters. © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.Peer Reviewe

The influence of synaptic size on AMPA receptor activation: A monte carlo model

© 2015 Montes et al. Physiological and electron microscope studies have shown that synapses are functionally and morphologically heterogeneous and that variations in size of synaptic junctions are related to characteristics such as release probability and density of postsynaptic AMPA receptors. The present article focuses on how these morphological variations impact synaptic transmission. We based our study on Monte Carlo computational simulations of simplified model synapses whose morphological features have been extracted from hundreds of actual synaptic junctions reconstructed by three-dimensional electron microscopy. We have examined the effects that parameters such as synaptic size or density of AMPA receptors have on the number of receptors that open after release of a single synaptic vesicle. Our results indicate that the maximum number of receptors that will open after the release of a single synaptic vesicle may show a ten-fold variation in the whole population of synapses. When individual synapses are considered, there is also a stochastical variability that is maximal in small synapses with low numbers of receptors. The number of postsynaptic receptors and the size of the synaptic junction are the most influential parameters, while the packing density of receptors or the concentration of extrasynaptic transporters have little or no influence on the opening of AMPA receptors. Copyright:Peer Reviewe