Laboratorios de Circuitos Neuronales

 

 

 

HFO_KArat

We are using multi-site silicon probes to record hippocampal oscillations. We look at rhythm distortion in the epileptic hippocampus using different experimental models that further allow us to propose new treatments for the human condition

Activity patterns of hippocampal circuits

The main goal of our lab is to understand the function of the hippocampal and para-hippocampal circuits in the normal and the epileptic brain. We are interested on how complex patterns of activity are produced with a special emphasis in the cellular and synaptic rules that govern circuit dynamics. To tackle these questions we use different in vitro and in vivo preparations. We focus in different forms of activity, including several types of oscillations (ripples, fast ripples, theta and gamma) and epileptiform events.

Different types of HFOs, in J Neurosc
In Utero>

We are using novel experimental models of cortical displasia and hippocampal heterotopias to better understand how to diagnose and treat this human condition. We also collaborate to further exploit genetic approaches aimed to interfer with development of specific cellular populations of the cerebral cortex and hippocampus, and to subsequently look at their impact in brain oscillations.

Rhythmopathies & developmental malformations

Most of the functional and structural specificity of neuronal circuitry emerges during early development through specific genetic programs. Recent research suggests that subtle alterations of this process might lead to brain dysfunction, including epilepsy, autism and schizophrenia. We are using different genetic and pharmacological approaches to interfere with brain development during different embryonic stages. We focus on models of hippocampal heterotopias and similar developmental malformations to look for the cellular and synaptic mechanisms underlying early onset dysfunction of rhythms and epilepsy.

Models of the heterotopic brain, in Frontiers Syst Neu
ChronicRat

Multi-electrode recording of hippocampal oscillations in temporal lobe epilepsy. We study normal and epileptic animals while they perform several behavioral tasks aimed to test for their cognitive abilities. These approaches allow us to understand how cognition is impaired in humans with epilepsy and to propose new treatments.

Neurophysiological correlates of TLE-associated memory deficts

Memory deficits represent a serious neuropsychological problem in people suffering from temporal lobe epilepsy (TLE). While seizures play major roles in such impairment, the interictal brain also displays severe distortion of the physiological rhythms involved in memory function. However, the impact of brain rhythmopathies in TLE-associated memory deficits remains poorly understood. We pursue for the basic mechanisms underlying distortion of hippocampal oscillations in TLE during the interictal period and their relationship with the most common memory deficits. We are using an arsenal of techniques including multi-site recordings, single-cell electrophysiology (tetrode, intracellular and juxtacellular recordings) and new behavioral paradigms for testing memory function and hippocampal oscillations.

LFP correlates of episodic-like memory deficits, in J Neurosci
MRI&Electrodes2

Intracranial EEG recordings from a TLE patient. Three-dimensional reconstruction of electrode contacts from post-implantation MRI showing sites where different types of epileptic events were recorded. See our paper in Nat Neu 14:627-634 (2011) for more details

Studies on human TLE

We aim to translate our research to clinical activities in collaboration with the Neurosurgery Unit at the Hospital de La Princesa in Madrid, and with the INSERM unit U739 at the Hôpital Pitié Salpêtrière at Paris. Our purpose is to develop tools for analyzing and interpreting the electrophysiological signals obtained during the clinical evaluation of patients suffering drug-resistant temporal lobe epilepsy (TLE). We use in vivo and in vitro (hippocampal and cortical slices) electrophysiological approaches.

In collaboration with: Richard Miles and Gilles Huberfeld in Paris[+]

Seizure transition, in Nat Neu
Tetrodo

We are now using SU-8 and a new MEMS fabrication designs to produce multisite probes for neural applications. In collaboration with the group of Rosa Villa at the CNM-CSIC at Barcelona and with the technological research center IKERLAN at Arrasate we designed a SU-8-based tetrode, as a proof-of-principle that this material can be used as a substrate for depth multisite recording probes.

Novel electrode design

Neuroscience is a constantly growing field and new approaches are required for further advances. Some of our scientific questions require new tools to allow us for detailed fine-scale exploration of neural activity. We are interested in designing and producing new multisite probes for high-density single-cell recording and integrated functionalities, including microfluidity channels, new material coating and optical stimulation. We also design our probes using custom services of most known companies (see probe A16x1-2mm-100 in Neuronexus)

Novel integrated micro-fluidic probes in Lab on a Chip
  • Liset M de la Prida

    Liset M de la Prida, PhD

    Lab Director

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  • Elena Cid

    Elena Cid, PhD

    TLE models and histology

    Immunostaining, histochemistry, epilepsy models, models of developmental malformations.

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  • Jorge Eugercios

    Jorge Eugercios, Student

    Histological studies

    Basic histology, immunostaining

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  • Beatriz Gal

    Beatriz Gal, PhD

    Histological studies

    Basic histology, camera lucida, cell-reconstruction, cell counting

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  • Daniel Gomez

    Daniel Gomez, PhD Student

    Mice electrophysiology

    Multi-electrode silicon probes, immunostaining, models of developmental malformations.

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  • Francois Laurent

    François Laurent, PhD

    Data analysis & Matlab

    Oscillations, theta and gamma activities.

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  • Diego Lopez-Pigozzi

    Diego Lopez-Pigozzi, PhD

    Tetrode recordings & sorting

    Unit recordings and data analysis.

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  • Alberto Sanchez-Aguilera

    Alberto Sanchez-Aguilera, PhD Student

    In vitro recordings

    In collaboration with Asun Colino, from the UCM. Patch recordings, intrinsic excitability.

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  • Manuel Valero

    Manuel Valero, PhD Student

    Chronic & in vivo recordings

    Tetrodes, single-cell recordings, multi-electrode silicon probes, behavioural electro.

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    Previous lab members:

  • Paloma Aivar, Madrid, Spain
  • Jorge Brotons, Instituto de Neurociencias Alicante, Spain
  • Marion Inostroza, University Tuebingen, Germany
  • David Martin-Lopez, Kings College London, UK
  • Elisa Bellistri, Istituto Neurologico Carlo Besta, Italy
  • Yoryani G Uzcategui, Le Havre, France
  • Eva Jimenez-Mateos, Royal College of Surgeons, Ireland

    Short-term visitors (minimum 2 weeks):

  • Jose Luis Fernandez-Torre, Hospital Marques de Valdecillas, Santander (2013)
  • Thomas Blauwblomme, Hôpital Necker Enfants Malades (2013)
  • Pawel Fidzinski, Charité Universitätsmedizin Berlin. Funded by IBRO-InEurope (2011)
  • Oana Chever, College de France. Funded by YITP-FENS (2012)
  • Beatrice Radu, University of Verona. Funded by YITP-FENS (2012)
  • Audrey Touzot, Institut de Biologie Valrose. Funded by University of Nice (2012)
Neuroreport

Neuroreport 13 (11):
1421-1425 (2002) PDF

Hippocampus

Hippocampus (2003) 13 (6):
728-744 PDF

Revista Neurologia

Rev Neurol. 42 (11):
663-667 (2006) PDF

  • E. Cid, D.Gomez-Dominguez, D. Martin-Lopez, B. Gal, F. Laurent, JM. Ibarz, F. Francis and L. Menendez de la Prida

    Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

    Front. Syst. Neurosci. 8:50 (2014)

    Link
  • P.Aivar, M.Valero, E.Bellistri, L.Menendez de la Prida

    Extracellular calcium controls the expression of two different forms of ripple-like hippocampal oscillations

    J Neuroscience. 34(8): 2989-3004 (2014)

    Link
  • M.Inostroza, JR.Brotons-Mas, F.Laurent, E.Cid, L.Menendez de la Prida

    Specific impairment of “What-Where-When” episodic-like memory in experimental models of temporal lobe epilepsy

    J Neuroscience. 33(45): 17749-17762 (2013)

    Link
  • E.Bellistri, J.Aguilar, JR.Brotons-Mas, G.Foffani, L.Menendez de la Prida

    Basic properties of somatosensory-evoked responses in the dorsal hippocampus of the rat.

    J Physiol. Mar 25 (2013)

    Link
  • A.Altuna, E.Bellistri, E.Cid, P.Aivar, B.Gal, J.Berganzo, G.Gabriel, A.Guimerà, R.Villa, LJ.Fernández, L.Menendez de la Prida

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

    Lab Chip. 2013 Feb 14 (2013)

    Link
  • Luz M.Suárez, E.Cid, B.Gal, M.Inostroza, Jorge R. Brotons-Mas, D. Gomez-Dominguez, L.Menendez de la Prida, José M. Solís.

    Systemic injection of kainic acid differently affects LTP magnitude depending on its epileptogenic efficiency.

    PLoS ONE 7(10): e48128 (2012)

    Link
  • A.Altuna, L.Menendez de la Prida, E.Bellistri, G.Gabriel, A.Guimerá, J.Berganzo, R.Villa, LJ.Fernández

    SU-8 based microprobes with integrated planar electrodes for enhanced neural depth recording.

    Biosens Bioelectron. 37(1):1-5 (2012)

    Link
  • M.Inostroza, E.Cid, L.Menendez de la Prida, C.Sandi

    Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats.

    PLoS ONE 7(6):e38959 (2012)

    Link Comment
  • JG. Jefferys JG, L. Menendez de la Prida, F. Wendling, A Bragin, M Avoli, I Timofeev, F Lopes da Silva

    Mechanisms of physiological and epileptic HFO generation.

    Prog Neurol 8, 250–264 (2012)

    Link
  • M.Inostroza, E.Cid, J.Brotons-Mas, B.Gal, P.Aivar, Y.G.Uzcategui, C.Sandi, L.Menendez de la Prida

    Hippocampal dependent spatial memory in the water maze is preserved in an experimental models of temporal lobe epilepsy.

    PLoS ONE 6(7) e22372 (2011)

    Link
  • G.Huberfeld, L.Menendez de la Prida, J.Pallud, I.Cohen, M.l Le Van Quyen,C.Adam, S.Clemenceau,.M.Baulac, R.Miles

    Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy.

    Nat Neu 14:627-634 (2011)

    Action Comment
  • L.Menendez de la Prida, A.Trevelyan

    Cellular mechanisms of high frequency oscillations in epilepsy: on the diverse sources of pathological actitivies.

    Epilepsy Research 97, 308-317 (2011)

    Action
  • S.Lodato, GS.Tomassy, E De Leonibus, YG. Uzcategui, G.Andolfi, M.Armentano, A.Touzot, JM Gaztelu, P.Arlotta, L.Menendez de la Prida, M.Stude

    Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy.

    J Neuroscience 31:4650-4662 (2011)

    Action
  • JM. Ibarz, G Foffani, E Cid, M Inostroza, L Menendez de la Prida

    Emergent dynamics of fast ripples in the epileptic hippocampus.

    J Neuroscience 30:16249-16261 (2010)

    PDF
  • A.Altuna, G.Gabriel, L.Menendez de la Prida, M.Tijero, A.Guimera, J.Berganzo, R.Salido, R.Villa, L.J. Fernandez

    SU-8-based microneedles for in vitro neural applications.

    J. Micromech. Microeng.20:064014-20 (2010)

    PDF
  • G.J. Ortega, L.Menendez de la Prida, R.G. Sola, J. Pastor

    Synchronization clusters of interictal activity in the lateral temporal cortex of epileptic patients: intraoperative electrocorticographic analisis.

    Epilepsia 49: 269-280 (2008)

    PDF
  • G. Foffani, Y.G. Uzcategui, B. Gal, L. Menendez de la Prida

    Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus.

    Neuron 55:930-941 (2007)

    PDF Comment Comment
  • L.Menendez de la Prida, S. Totterdell, J. Gigg, R. Miles.

    The subiculum comes of age.

    Hippocampus (2006) 16: 916-923

    PDF
  • J.Pastor, L. Menendez de la Prida, V. Hernando, R. G. Sola.

    Voltage sources in mesial temporal lobe epilepsy recorded with foramen ovale electrodes.

    Clin Neurophysiol (2006) 117(12):2604-14

    PDF
  • L.Menendez de la Prida

    Functional features of the rat subicular microcircuits studied in vitro.

    Behav Brain Res (2006) 174: 198-205

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  • L. Menendez de la Prida, Gilles Huberfeld, Ivan Cohen, and Richard Miles.

    Threshold behavior in the initiation of hippocampal population bursts.

    Neuron (2006) 49:131-142

    PDF
  • L. Menendez de la Prida and B. Gal.

    Synaptic contributions to focal and widespread spatiotemporal dynamics in the isolated rat subiculum in vitro.

    J Neuroscience (2004) 24:5525-5536

    PDF
  • L. Menendez de la Prida

    Control of bursting by local inhibition in the subiculum in vitro.

    J Physiol (2003) 549:219-230

    PDF
  • L.Menendez de la Prida, F.Suarez and M.A.Pozo.

    Electrophysiological and morphological diversity of neurons from the rat subicular complex in vitro.

    Hippocampus (2003) 13 (6): 728-744

    PDF
  • L.Menendez de la Prida, R.Benavides-Piccione, R.Sola and M.A.Pozo.

    Electrophysiological properties of interneurons from intraoperative spiking areas of epileptic human temporal neocortex.

    Neuroreport 13 (11): 1421-1425 (2002)

    PDF
  • L.Menendez de la Prida and M.A.Pozo.

    Excitatory and inhibitory control of epileptiform discharges in combined hippocampal/entorhinal cortical slices.

    Brain Research 940:27-35 (2002)

    PDF
  • L.Menendez de la Prida, F.Suarez and M.A.Pozo.

    The effect of different morphological sampling criteria on the fraction of bursting cells recorded in the subiculum in vitro.

    Neurosci.Lett. 322: 49-52 (2002)

    PDF
  • L.Menendez de la Prida and J.V.Sanchez-Andres.

    Heterogenous neuronal population underly synchronous bursting in the developing hippocampus through a frequency-dependent mechanism.

    Neuroscience 97 (2) : 227-241 (2000)

    PDF
  • L.Menendez de la Prida and J.V.Sanchez-Andres.

    Nonlinear transfer function encodes synchronization in a neural network from the mammaliam brain.

    Phys.Rev.E. 60 (3) 3239-3243 (1999)

    PDF
  • L.Menendez de la Prida and J.V.Sanchez-Andres.

    Nonlinear frequency-dependent synchronization in the developing hippocampus.

    J.Neurophysiol 82, 202-208 (1999)

    PDF
  • L.Menendez de la Prida, S.Bolea and J.V.Sanchez-Andres.

    Origin of the synchronized network activity in the rabbit developing hippocampus.

    Eur.J.Neurosci. 10, 899-906 (1998)

    PDF
  • L.Menendez de la Prida, N.Stollenwerk and J.V.Sanchez-Andres.

    Bursting as a source for predictability in the neural networks activity.

    Physica D 110, 323-331 (1997)

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  • L.Menendez de la Prida, S.Bolea and J.V.Sanchez-Andres.

    Analytical characterization of the evolution of spontaneous activity in early hippocampal development in rabbit.

    Neurosc.Lett. 218 (1996) 185-187

    PDF
  • R.V.Sole and L. Menendez de la Prida.

    Controlling chaos in discrete neural networks.

    Physics Letters A 199 (1995), 65-69

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Our work is currently supported by grants from:

  • Spanish Ministry of Science and Technology The Spanish Ministry of Science and Technology (BFU2012-37156-C03-01)
  • HFSP Human Fontiers Science Program (with JC Poncer, Y Hayashi and A.Ting)

    Previous grants:

  • The European ERANET-Neuron Program 2009-2013 (EpiNet)
  • European Commission-FP6 (STREP Contract 005139 INTERDEVO) and FP-7 (MemStick)
  • Fundación Alicia Koplowitz
  • Spanish Ministry of Science and Technology (BFI2003-04305, BFU2006-10584,SAF2005-23977,BFU2009-07989)
  • Joint Action with the French Ministry of Education and Science (HF2006-0082)
  • Comunidad de Madrid (GR/SAL/0131/2004)