Emergent dynamics of fast ripples in the epileptic hippocampus

Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100-400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in >pure> fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in >emergent> fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo.We found that in-phase firing can reach frequencies up to 300 Hz in the CA1and up to 400Hzin the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus. Copyright © 2010 the authors.Peer Reviewe

Empleo de Actividades Interactivas como Apoyo en el Desarrollo de Competencias en Temas de Probabilidad y Estadística

Ponencia del V Foro de Investigación Educativ

Systemic Injection of Kainic Acid Differently Affects LTP Magnitude Depending on its Epileptogenic Efficiency

Seizures have profound impact on synaptic function and plasticity. While kainic acid is a popular method to induce seizures and to potentially affect synaptic plasticity, it can also produce physiological-like oscillations and trigger some forms of long-term potentiation (LTP). Here, we examine whether induction of LTP is altered in hippocampal slices prepared from rats with different sensitivity to develop status epilepticus (SE) by systemic injection of kainic acid. Rats were treated with multiple low doses of kainic acid (5 mg/kg; i.p.) to develop SE in a majority of animals (72-85% rats). A group of rats were resistant to develop SE (15-28%) after several accumulated doses. Animals were subsequently tested using chronic recordings and object recognition tasks before brain slices were prepared for histological studies and to examine basic features of hippocampal synaptic function and plasticity, including input/output curves, paired-pulse facilitation and theta-burst induced LTP. Consistent with previous reports in kindling and pilocapine models, LTP was reduced in rats that developed SE after kainic acid injection. These animals exhibited signs of hippocampal sclerosis and developed spontaneous seizures. In contrast, resistant rats did not become epileptic and had no signs of cell loss and mossy fiber sprouting. In slices from resistant rats, theta-burst stimulation induced LTP of higher magnitude when compared with control and epileptic rats. Variations on LTP magnitude correlate with animals' performance in a hippocampal-dependent spatial memory task. Our results suggest dissociable long-term effects of treatment with kainic acid on synaptic function and plasticity depending on its epileptogenic efficiency. © 2012 Suárez et al.Peer Reviewe

Me gusta como soy : experiencia de salud mental, educación sexual y prevención de drogodependencias en el Colegio Público San Sebastián de Castelseras (Teruel)

Encuadernado con : Nuestra sexualidad, nuestra vida. En la cub. : Educación para la Salud en Enseñanza Secundaria (primer ciclo). Programa experimental de educación para la salud en la escuelaLos objetivos del proyecto son proporcionar al alumnado la información adecuada y completa sobre los temas de sexualidad, salud mental y dependencias (tabaco y alcohol) y procurar un cambio profundo de actitudes y conductas hacia un estilo de vida más saludable. Se realizan con los alumnos actividades en el aula (charlas, debates, encuestas, puestas en común, visionado de vídeos, sociogramas, dramatización), y con los padres y miembros del APA (reuniones informativas, charlas y seminarios).AragónBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5; 28014 Madrid; Tel. +34917748000; [email protected]

Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples

Sharp-wave ripples represent a prominent synchronous activity pattern in the mammalian hippocampus during sleep and immobility. GABAergic interneuronal types are silenced or fire during these events, but the mechanism of pyramidal cell (PC) participation remains elusive. We found opposite membrane polarization of deep (closer to stratum oriens) and superficial (closer to stratum radiatum) rat CA1 PCs during sharp-wave ripples. Using sharp and multi-site recordings in combination with neurochemical profiling, we observed a predominant inhibitory drive of deep calbindin (CB)-immunonegative PCs that contrasts with a prominent depolarization of superficial CB-immunopositive PCs. Biased contribution of perisomatic GABAergic inputs, together with suppression of CA2 PCs, may explain the selection of CA1 PCs during sharp-wave ripples. A deep-superficial gradient interacted with behavioral and spatial effects to determine cell participation during sleep and awake sharp-wave ripples in freely moving rats. Thus, the firing dynamics of hippocampal PCs are exquisitely controlled at subcellular and microcircuit levels in a cell type–selective manner.This work was supported by a grant from the Spanish Ministerio de Economía y Competitividad (BFU2012-37156-C03-01). E.C. receives funding from the CSIC JAE Program, co-funded by the European Social Fund. M.V. was supported by the Spanish Ministry of Education, Culture and Sports (FPU12/03776) and by a short-term grant to visit the MRC Anatomical Neuropharmacological Unit in Oxford (FPU-EST13/01046). A.S.-A. is funded by the Universidad Complutense de Madrid. T.J.V. was supported by the UK Medical Research Council. R.G.A. was supported by an ERC Advanced grant (INTERIMPACT) to G. Tamás. D.G.-D. is funded by the Spanish Ministerio de Economía y Competitividad (BES-2013-064171)

Mechanisms for Selective Single-Cell Reactivation during Offline Sharp-Wave Ripples and Their Distortion by Fast Ripples

Memory traces are reactivated selectively during sharp-wave ripples. The mechanisms of selective reactivation, and how degraded reactivation affects memory, are poorly understood. We evaluated hippocampal single-cell activity during physiological and pathological sharp-wave ripples using juxtacellular and intracellular recordings in normal and epileptic rats with different memory abilities. CA1 pyramidal cells participate selectively during physiological events but fired together during epileptic fast ripples. We found that firing selectivity was dominated by an event- and cell-specific synaptic drive, modulated in single cells by changes in the excitatory/inhibitory ratio measured intracellularly. This mechanism collapses during pathological fast ripples to exacerbate and randomize neuronal firing. Acute administration of a use- and cell-type-dependent sodium channel blocker reduced neuronal collapse and randomness and improved recall in epileptic rats. We propose that cell-specific synaptic inputs govern firing selectivity of CA1 pyramidal cells during sharp-wave ripples.Supported by grants from the Spanish Ministerio de Economía y Competitividad (MINECO) to L.M.P. (BFU2012-37156-C03-01 and BFU2015-66887-R). M.V. was supported by a PhD fellowship from the Spanish Ministry of Education, Culture and Sports (FPU12/03776). R.G.A. and G.T. were supported by the ERC Interimpact project, the Hungarian Academy of Sciences, the Hungarian National Office for Research and Technology GINOP-2.3.2-15-2016-00018, and by the National Brain Research Program, Hungary

Altered oscillatory dynamics of CA1 parvalbumin basket cells during theta-gamma rhythmopathies of temporal lobe epilepsy

© 2016 Lopez-Pigozzi et al.Recent reports in human demonstrate a role of theta–gamma coupling in memory for spatial episodes and a lack of coupling in people experiencing temporal lobe epilepsy, but the mechanisms are unknown. Using multisite silicon probe recordings of epileptic rats engaged in episodic-like object recognition tasks, we sought to evaluate the role of theta–gamma coupling in the absence of epileptiform activities. Our data reveal a specific association between theta–gamma (30–60 Hz) coupling at the proximal stratum radiatum of CA1 and spatial memory deficits. We targeted the microcircuit mechanisms with a novel approach to identify putative interneuronal types in tetrode recordings (parvalbumin basket cells in particular) and validated classification criteria in the epileptic context with neurochemical identification of intracellularly recorded cells. In epileptic rats, putative parvalbumin basket cells fired poorly modulated at the falling theta phase, consistent with weaker inputs from Schaffer collaterals and attenuated gamma oscillations, as evaluated by theta-phase decomposition of current–source density signals. We propose that theta–gamma interneuronal rhythmopathies of the temporal lobe are intimately related to episodic memory dysfunction in this condition.This research was supported by Spanish Ministerio de Economía y Competitividad Grants BFU2012-37156-C03-01 and BFU2015-66887-R. M. Valero holds a PhD fellowship (FPU12/03776) from the Spanish Ministry of Education, Culture and Sports. D.G.D. is funded by Spanish Ministerio de Economía y Competitividad Grant BES-2013-064171

SU-8 based microprobes for simultaneous neural depth recording and drug delivery in the brain

While novel influential concepts in neuroscience bring the focus to local activities generated within a few tens of cubic micrometers in the brain, we are still devoid of appropriate tools to record and manipulate pharmacologically neuronal activity at this fine scale. Here we designed, fabricated and encapsulated microprobes for simultaneous depth recording and drug delivery using exclusively the polymer SU-8 as structural material. A tetrode- and linear-like electrode patterning was combined for the first time with single and double fluidic microchannels for independent drug delivery. The device was tested experimentally using the in vivo anesthetized rat preparation. Both probe types successfully recorded detailed spatiotemporal features of local field potentials and single-cell activity at a resolution never attained before with integrated fluidic probes. Drug delivery was achieved with high spatial and temporal precision in a range from tens of nanoliters to a few microliters, as confirmed histologically. These technological advancements will foster a wide range of neural applications aimed at simultaneous monitoring of brain activity and delivery at a very precise micrometer scale. This journal is © 2013 The Royal Society of Chemistry.Peer Reviewe