Lucia Wittner

Lucia Wittner
Research Center for Natural Sciences, Budapest, Hungary · Institute of Cognitive Neuroscience and Psychology

PhD

About

65
Publications
7,193
Reads
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2,790
Citations
Introduction
Interested in cellular and network mechanisms of physiological and pathological (epileptic) synchrony generation, mainly in humans. We investigate this topic with a combined in vivo and in vitro electrophysiology, two-photon imaging, completed with anatomical examinations including light and electron microscopy.
Additional affiliations
February 2006 - present
Research Center of Natural Sciences, Hungarian Academy of Sciences
Position
  • Senior Researcher
February 2004 - January 2006
French Institute of Health and Medical Research
Position
  • PostDoc Position
January 2001 - March 2002
Center for Molecular and Behavioral Neuroscience, Rutgers University
Position
  • Research Assistant
Education
September 1999 - January 2004
Semmelweis University
Field of study
  • Neurosciences
September 1994 - June 1999
Eötvös Loránd University
Field of study
  • Biology

Publications

Publications (65)
Article
Full-text available
Knowledge about the activity of single neurons is essential in understanding the mechanisms of synchrony generation, and particularly interesting if related to pathological conditions. The generation of interictal spikes—the hypersynchronous events between seizures—is linked to hyperexcitability and to bursting behaviour of neurons in animal models...
Article
Intrinsically disordered proteins (IDPs) play important roles in disease pathologies; however, their lack of defined stable 3D structures make traditional drug design strategies typically less effective against these targets. Based on promising results of targeted covalent inhibitors (TCIs) on challenging targets, we have developed a covalent desig...
Article
Full-text available
Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroug...
Preprint
Full-text available
Cortical dynamics obey a 1/f power law, exhibiting an exponential decay of spectral power with increasing frequency. The slope and offset of this 1/f decay reflect the timescale and magnitude of aperiodic neural activity, respectively. These properties are tightly linked to cellular and circuit mechanisms (e.g. excitation:inhibition balance, firing...
Article
Full-text available
Sleep spindles are functionally important NREM sleep EEG oscillations which are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patte...
Article
Objective The goal of this study was to define the pathology and anesthesia dependency of single pulse electrical stimulation (SPES) dependent high-frequency oscillations (HFOs, ripples, fast ripples) in the hippocampal formation. Methods Laminar profile of electrically evoked short latency (<100 ms) high-frequency oscillations (80−500 Hz) was exa...
Article
Full-text available
The first representatives of fluorescent boro-β-carbolines were applied for labeling trastuzumab. The antibody fluorophore conjugate was confirmed as a useful tool for labeling and imaging tumour cells in confocal and two-photon microscopy.
Article
Full-text available
The use of SU-8 material in the production of neural sensors has grown recently. Despite its widespread application, a detailed systematic quantitative analysis concerning its biocompatibility in the central nervous system is lacking. In this immunohistochemical study, we quantified the neuronal preservation and the severity of astrogliosis around...
Article
Full-text available
The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We f...
Article
Key points: Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network both in humans and animals. Here we show that epileptiform interictal-like spikes and seizures emerged in human neocortical slices by blocking GABAA receptors, following the disappearance of the...
Conference Paper
Full-text available
Here we show, that based on parallel multichannel extracellular and single channel intracellular potential recordings, it is possible the reconstruct the spatio-temporal distribution of membrane potential with the spatial resolution of the extracellular recordings in single neurons. Moreover we show, that reconstruction of membrane potential made p...
Preprint
Full-text available
Sleep spindles are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epi...
Preprint
Full-text available
The alpha rhythm is the longest studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used micro and macro electrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first foun...
Article
Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual ins...
Article
Key points: Hyperexcitability and hypersynchrony of neuronal networks are thought to be linked to the generation of epileptic activity in both humans and animal models. Here we show that human epileptic postoperative neocortical tissue is able to generate two different types of synchronies in vitro. Epileptiform bursts occurred only in slices deri...
Data
skCSD reconstruction of current source density distribution on the ganglion cell. The video shows the skCSD reconstruction for the retinal ganglion cell model driven with oscillatory current (Section Reconstruction of current distribution on complex morphology) for the whole duration of simulation. Figure 7 shows a snapshot taken at t = 495.25 ms f...
Data
S1 Video skCSD reconstruction of current source density distribution on the ganglion cell. The video shows the skCSD reconstruction for the retinal ganglion cell model driven with oscillatory current (Section Reconstruction of current distribution on complex morphology) for the whole duration of simulation. Figure 7 shows a snapshot taken at t = 49...
Data
S2 Video Spike triggered average of pyramidal cell in vitro. The video shows the recorded potentials and skCSD reconstruction for a 10 ms time window centered around the spike as described in Section Proof of Concept experiment: Spatial Current Source Distribution of Spike-triggered Averages. The top panel presents the spike triggered averages of t...
Preprint
Sleep spindles are a cardinal feature in human slow wave sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in humans by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspe...
Article
Full-text available
Revealing the current source distribution along the neuronal membrane is a key step on the way to understanding neural computations, however, the experimental and theoretical tools to achieve sufficient spatiotemporal resolution for the estimation remain to be established. Here we address this problem using extracellularly recorded potentials with...
Article
The effects of the environment on the mood and behaviour is in the focus of current brain research. All of us certainly have personal observations within this topic, like how much children love places with numerous colourful toys, or that people usually feel better in a bright and picturesque milieu compared to dark and dull places. This article is...
Preprint
Full-text available
Revealing the membrane current source distribution of neurons is a key step on the way to understanding neural computations, however, the experimental and theoretical tools to achieve sufficient spatiotemporal resolution for the estimation remain to be established. Here we address this problem using extracellularly recorded potentials with arbitrar...
Article
Full-text available
GABAergic inhibition and particularly perisomatic inhibition play a crucial role in controlling the firing properties of large principal cell populations. Furthermore, GABAergic network is a key element in the therapy attempting to reduce epileptic activity. Here, we present a review showing the synaptic changes of perisomatic inhibitory neuronal s...
Article
Full-text available
Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role...
Article
Full-text available
Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. Here, we demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated CMOS ele...
Article
Rhythmic slow waves characterize brain electrical activity during natural deep sleep and under anesthesia, reflecting the synchronous membrane potential fluctuations of neurons in the thalamocortical network. Strong evidence indicates that the neocortex plays an important role in the generation of slow wave activity (SWA), however, contributions of...
Article
Full-text available
Spontaneous synchronous population activity (SPA) can be detected by electrophysiological methods in cortical slices of epileptic patients, maintained in a physiological medium in vitro. In order to gain additional spatial information about the network mechanisms involved in the SPA generation, we combined electrophysiological studies with two-phot...
Article
Full-text available
Hippocampal sharp wave-ripples (SPW-Rs) occur during slow wave sleep and behavioral immobility and are thought to play an important role in memory formation. We investigated the cellular and network properties of SPW-Rs with simultaneous laminar multielectrode and intracellular recordings in a rat hippocampal slice model, using physiological bathin...
Article
Abstract In this article, we evaluated the electrophysiological performance of a novel, high-complexity silicon probe array. This brain-implantable probe implements a dynamically reconfigurable voltage-recording device, coordinating large numbers of electronically switchable recording sites, referred to as electronic depth control (EDC). Our result...
Article
Full-text available
Cortical electrical activity during nonrapid eye movement (non-REM) sleep is dominated by slow-wave activity (SWA). At larger spatial scales (∼2-30 cm), investigated by scalp EEG recordings, SWA has been shown to propagate globally over wide cortical regions as traveling waves, which has been proposed to serve as a temporal framework for neural pla...
Article
Our study confirmed the hypothesis of Amzica and Steriade that the human K-complex (KC) shares neural mechanisms with so-called slow oscillation between periods of intense neuronal firing and silence, but found that the KC can occur independently of this oscillatory activity. We agree with Amzica that the KC often has multiple components but conten...
Article
Full-text available
We report gene profiling data on genomic processes underlying the progression towards recurrent seizures after injection of kainic acid (KA) into the mouse hippocampus. Focal injection enabled us to separate the effects of proepileptic stimuli initiated by KA injection. Both the injected and contralateral hippocampus participated in the status epil...
Article
Full-text available
Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates d...
Chapter
Changes in neuronal chloride homeostasis affect GABAA receptor-mediated transmission and may contribute to epileptic activities. Work on human epileptic tissue suggests that Cl− homeostasis is impaired in some temporal lobe pyramidal cells. GABAergic depolarization of these neurons contributes to rhythmic, interictal events. Intra-neuronal Cl− is c...
Article
Full-text available
The dentate gyrus, the cornu ammonis 2 region and the subiculum of the human hippocampal formation are resistant to the cell loss associated with temporal lobe epilepsy. The subiculum, but not the dentate gyrus, generates interictal-like activity in tissue slices from epileptic patients. In this study, we asked whether a similar population activity...
Article
Full-text available
The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we...
Article
Biocompatibility and the impact of different coatings on four shank NeuroProbes silicon multielectrodes were investigated in vivo. Effects of uncoated silicon (Si), hyaluronic acid (Hya), dextrane (Dex), dexamethasone (DexM) and Hya/DexM coatings on neuronal and glial densities were examined in the rat neocortex. Tissue reaction was explored with n...
Article
Full-text available
Drug-resistant partial epilepsies, including temporal lobe epilepsies with hippocampal sclerosis and cortical dysplasias, offer the opportunity to study human epileptic activity in vitro since the preferred therapy often consists of the surgical removal of the epileptogenic zone. Slices of this tissue retain functional neuronal networks and may gen...
Article
Full-text available
A large proportion of hippocampal afferents and efferents are relayed through the subiculum. It is also thought to be a key structure in the generation and maintenance of epileptic activity; rhythmic interictal-like discharges were recorded in previous studies of subicular slices excised from temporal lobe epilepsy patients. In order to investigate...
Article
This paper introduces the first experimental results of a new implantable slim-base three-dimensional (3D) probe array for cerebral applications. The probes are assembled perpendicularly into the slim-base readout platform where electrical and mechanical connections are achieved simultaneously. A new type of micromachined interconnect has been deve...
Article
Synchronous activities of neuronal populations are often initiated in a pacemaker region and spread to recruit other regions. Here we examine factors that define a pacemaker site. The CA3a region acts as the pacemaker for disinhibition induced synchrony in guinea pig hippocampal slices and CA3b is a follower region. We found CA3a pyramidal cells we...
Article
Full-text available
Changes in chloride (Cl-) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl- homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this human tissue generated a spontaneo...
Article
Full-text available
The three-dimensional intrahippocampal distribution of axon collaterals of an in vivo filled CA3c pyramidal cell was investigated. The neuron was filled with biocytin in an anesthetized rat and the collaterals were reconstructed with the aid of a NeuroLucida program from 48 coronal sections. The total length of the axon collaterals exceeded 0.5 m,...
Article
Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of e...
Article
031NEUROGENESIS IN EPILEPTIC BRAIN: AFFERENT SYNAPSES TO NEWBORN CELLS ATTENUATE NETWORK EXCITABILITY 1M.Kokaia ( Wallenberg Neuroscience Center, Lund University Hospital, Sweden ) Purpose: Neural stem cells in the adult mammalian brain (including humans) continue to produce new functional granule cells in the dentate gyrus subgranular zone and new...
Article
The specific connectivity among principal cells and interneurons determines the flow of activity in neuronal networks. To elucidate the connections between hippocampal principal cells and various classes of interneurons, CA3 pyramidal cells were intracellularly labelled with biocytin in anaesthetized rats and the three-dimensional distribution of t...
Article
Intra-hippocampal kainate injection induces an epileptiform activity termed status epilepticus. We examined the emergence of this activity with extracellular and intracellular records of responses (1) to focal kainate (KA) application in slices of mouse hippocampus and (2) of slices from mice injected with KA. The effects varied with distance from...
Article
Full-text available
Temporal lobe epilepsy (TLE) is known to be linked to an impaired balance of excitation and inhibition. Whether inhibition is decreased or preserved in the human epileptic hippocampus, beside the excess excitation, is still a debated question. In the present study, quantitative light and electron microscopy has been performed to analyse the distrib...
Article
Full-text available
Processing of neuronal information depends on interactions between the anatomical connectivity and cellular properties of single cells. We examined how these computational building blocks work together in the intact rat hippocampus. Single spikes in dentate granule cells, controlled intracellularly, generally failed to discharge either interneurons...
Article
Hippocampal activity in vivo is characterized by concurrent oscillations at theta (4-15 Hz) and gamma (20-80 Hz) frequencies. Here we show that cholinergic receptor activation (methacholine 10-20 nm) in hippocampal slice cultures induces an oscillatory mode of activity, in which the intrinsic network oscillator (located in the CA3 area) expresses s...
Article
The distribution, morphology, synaptic coverage and postsynaptic targets of calbindin-containing interneurons and afferent pathways have been analyzed in the control and epileptic CA1 region of the human hippocampus. Numerous calbindin-positive interneurons are preserved even in the strongly sclerotic CA1 region. The morphology of individual cells...
Article
Temporal lobe epilepsy is known to be associated with hyperactivity that is likely to be generated or amplified in the hippocampal formation. The majority of granule cells, the principal cells of the dentate gyrus, are found to be resistant to damage in epilepsy, and may serve as generators of seizures if their inhibition is impaired. Therefore, th...