- Hippocampal activity
in health and epilepsy - The hippocampus in developmental epilepsy
- TLE-associated
memory deficits - Translational research: studies on human TLE
- Novel microengineered probe desing
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, as well as computational tools including realistic models based in the Hodgkin-Huxley formalism and machine learning algorithms for pattern recognition. We focus in studying different forms of activity, including several types of oscillations (ripples, fast ripples, theta and gamma) and epileptiform events.
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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.
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.
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[+]
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)
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Liset M de la Prida, PhD
Lab Director
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Elena Cid, PhD
Histology and genetic approaches
Single-cell profiling, viral techniques, epilepsy models.
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Ivan Fernandez de Lamo, PhD
In vivo recordings
Single-cell recordings, multi-electrode silicon probes.
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Beatriz Gal, PhD
Histological studies
Basic histology, camera lucida, cell-reconstruction, cell counting
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Daniel Gomez, PhD Student
Oscillations and rhythmopathies
Multi-electrode recordings, multi-cellular Ca imaging, DREADDs.
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Beatriz Lázaro
Technician
Tissue processing, epilepsy models and colony handling
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Manuel Valero, PhD Student
Chronic & in vivo recordings
Single-cell recordings, multi-electrode silicon probes, behavioural ephys.
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- François Laurent, Institut Pasteur; Paris, France
- Diego Lopez-Pigozzi, KOKI, Budapest, Hungary
- Paloma Aivar, Universidad Europea de Madrid, Spain
- Jorge Brotons-Mas, 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
Previous lab members:
- Giuditta Gambino, Universita di Palermo, Italy (2016)
- Marie Goutierre, Institut fer-a-moulin, Paris, France (2014)
- 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)
Short-term visitors (>2 weeks):
Neuroreport 13 (11):
1421-1425 (2002)
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Hippocampus (2003) 13 (6):
728-744
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Rev Neurol. 42 (11):
663-667 (2006)
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Altered oscillatory dynamics of CA1 parvalbumin basket cells during theta–gamma rhythmopathies of temporal lobe epilepsy
eNeuro 3 (6), 0284-16.2016 (2016)
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Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples
Nature Neuroscience 18, 1281–1290 (2015).
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Simplest relationship between local field potential and intracellular signals in layered neural tissue
Phys. Rev. E 92, 062704 (2015).
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Conundrums of high-frequency oscillations (80-800 Hz) in the epileptic brain
J Clin Neurophysiol. 32(3):207-19(2015).
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Proximodistal structure of theta coordination in the dorsal hippocampus of epileptic rats
J Neuroscience. 35(11): 4760-4775 (2015)
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Different mechanisms of ripple-like oscillations in the human epileptic subiculum
Ann Neurol. 77(2):281-90 (2015).
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Function of inhibitory micronetworks is spared by Na+ channel-acting anticonvulsant drugs
J Neuroscience. 34(29):9720-9735 (2014)
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Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations
Front. Syst. Neurosci. 8:50 (2014)
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Extracellular calcium controls the expression of two different forms of ripple-like hippocampal oscillations
J Neuroscience. 34(8): 2989-3004 (2014)
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Specific impairment of “What-Where-When” episodic-like memory in experimental models of temporal lobe epilepsy
J Neuroscience. 33(45): 17749-17762 (2013)
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Basic properties of somatosensory-evoked responses in the dorsal hippocampus of the rat.
J Physiol. Mar 25 (2013)
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SU-8 based microprobes for simultaneous neural depth recording and drug delivery in the brain.
Lab Chip. 2013 Feb 14 (2013)
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Systemic injection of kainic acid differently affects LTP magnitude depending on its epileptogenic efficiency.
PLoS ONE 7(10): e48128 (2012)
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SU-8 based microprobes with integrated planar electrodes for enhanced neural depth recording.
Biosens Bioelectron. 37(1):1-5 (2012)
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Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats.
PLoS ONE 7(6):e38959 (2012)
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Mechanisms of physiological and epileptic HFO generation.
Prog Neurol 8, 250–264 (2012)
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Hippocampal dependent spatial memory in the water maze is preserved in an experimental models of temporal lobe epilepsy.
PLoS ONE 6(7) e22372 (2011)
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Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy.
Nat Neu 14:627-634 (2011)
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Cellular mechanisms of high frequency oscillations in epilepsy: on the diverse sources of pathological actitivies.
Epilepsy Research 97, 308-317 (2011)
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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)
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Emergent dynamics of fast ripples in the epileptic hippocampus.
J Neuroscience 30:16249-16261 (2010)
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SU-8-based microneedles for in vitro neural applications.
J. Micromech. Microeng.20:064014-20 (2010)
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Synchronization clusters of interictal activity in the lateral temporal cortex of epileptic patients: intraoperative electrocorticographic analisis.
Epilepsia 49: 269-280 (2008)
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Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus.
Neuron 55:930-941 (2007)
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The subiculum comes of age.
Hippocampus (2006) 16: 916-923
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Voltage sources in mesial temporal lobe epilepsy recorded with foramen ovale electrodes.
Clin Neurophysiol (2006) 117(12):2604-14
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Functional features of the rat subicular microcircuits studied in vitro.
Behav Brain Res (2006) 174: 198-205
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Threshold behavior in the initiation of hippocampal population bursts.
Neuron (2006) 49:131-142
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Synaptic contributions to focal and widespread spatiotemporal dynamics in the isolated rat subiculum in vitro.
J Neuroscience (2004) 24:5525-5536
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Control of bursting by local inhibition in the subiculum in vitro.
J Physiol (2003) 549:219-230
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Electrophysiological and morphological diversity of neurons from the rat subicular complex in vitro.
Hippocampus (2003) 13 (6): 728-744
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Electrophysiological properties of interneurons from intraoperative spiking areas of epileptic human temporal neocortex.
Neuroreport 13 (11): 1421-1425 (2002)
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Excitatory and inhibitory control of epileptiform discharges in combined hippocampal/entorhinal cortical slices.
Brain Research 940:27-35 (2002)
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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)
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Heterogenous neuronal population underly synchronous bursting in the developing hippocampus through a frequency-dependent mechanism.
Neuroscience 97 (2) : 227-241 (2000)
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Nonlinear transfer function encodes synchronization in a neural network from the mammaliam brain.
Phys.Rev.E. 60 (3) 3239-3243 (1999)
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Nonlinear frequency-dependent synchronization in the developing hippocampus.
J.Neurophysiol 82, 202-208 (1999)
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Origin of the synchronized network activity in the rabbit developing hippocampus.
Eur.J.Neurosci. 10, 899-906 (1998)
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Bursting as a source for predictability in the neural networks activity.
Physica D 110, 323-331 (1997)
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Analytical characterization of the evolution of spontaneous activity in early hippocampal development in rabbit.
Neurosc.Lett. 218 (1996) 185-187
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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:
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Ministerio de Economía y Competitividad (BFU2015-66887-R)
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Human Fontiers Science Program (with JC Poncer, Y Hayashi and A.Ting)
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Fundación Tatiana Pérez de Guzmán el Bueno
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ERANET-Neuron (with C Rivera, JC Poncer, F Guillemot and CA Hübner)
- The European ERANET-Neuron Program 2009-2013 (EpiNet)
- European Commission FP6 (STREP Contract 005139 INTERDEVO) and FP7 (MemStick)
- Fundación Alicia Koplowitz
- Gobierno de España (BFI2003-04305, BFU2006-10584, SAF2005-23977, BFU2009-07989, BFU2012-37156-C03-01)
- Joint Action with the French Ministry of Education and Science (HF2006-0082)
- Comunidad de Madrid (GR/SAL/0131/2004)