Liset M de la Prida

Liset M de la Prida
Cajal Institute · Functional and Systems Neuroscience

Professor
Hippocampal microcircuits in health and disease http://hippo-circuitlab.es/ Twitter & IG: @LMPrida

About

83
Publications
11,850
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,937
Citations
Introduction
Liset M de la Prida leads the Laboratorio de Circuitos Neuronales at the Instituto Cajal in Madrid. The main goal of her lab is to understand the function of hippocampal and para-hippocampal circuits in the normal and the epileptic brain using a combination of state-of-the-art techniques. Visit our website: http://hippo-circuitlab.es/

Publications

Publications (83)
Article
Integration of plasmonic structures on step‐index optical fibers is attracting interest for both applications and fundamental studies. However, the possibility to dynamically control the coupling between the guided light fields and the plasmonic resonances is hindered by the turbidity of light propagation in multimode fibers (MMFs). This pivotal po...
Article
In article number 2101649, Filippo Pisano and co-workers demonstrate a first step towards implantable multimodal plasmonic neural interfaces. This was achieved by integrating highly-curved plasmonic nanostructures on a tapered optical fiber in order to engineer the spectral and angular patterns of optical emission and collection, with applications...
Article
Full-text available
Optical methods are driving a revolution in neuroscience. Ignited by optogenetic techniques, a set of strategies has emerged to control and monitor neural activity in deep brain regions using implantable photonic probes. A yet unexplored technological leap is exploiting nanoscale light-matter interactions for enhanced bio-sensing, beam-manipulation...
Article
Full-text available
Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on ento...
Preprint
Full-text available
Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type specific vulnerability, their progression and histopathological classification remain controversial. Here using single-cell electrophysiology in vivo and immediate early gene exp...
Article
Full-text available
Pathogenesis of Peritumoral Hyperexcitability in an Immunocompetent CRISPR-Based Glioblastoma Model Hatcher A, Yu K, Meyer J, Aiba I, Deneen B, Noeb JL. J Clin Invest. 2020;130(5):2286-2300. doi:10.1172/JCI133316 Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular patho...
Article
Sharp-wave ripples are complex neurophysiological events recorded along the trisynaptic hippocampal circuit (i.e. from CA3 to CA1 and the subiculum) during slow-wave sleep and awake states. They arise locally but scale brain-wide to the hippocampal target regions at cortical and subcortical structures. During these events, neuronal firing sequences...
Article
Full-text available
Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioral sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type-specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase prefere...
Preprint
Full-text available
Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioural sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase prefer...
Article
Full-text available
Complex Oscillatory Waves Emerging From Cortical Organoids Model Early Human Brain Network Development Trujillo CA, Gao R, Negraes PD, et al. Cell Stem Cell. 2019;25(4):558-569.e7. doi:10.1016/j.stem.2019.08.002. Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, wh...
Article
Full-text available
Prenatal exposure to Δ9-tetrahydrocannabinol (THC), the most prominent active constituent of cannabis, alters neurodevelopmental plasticity with a long-term functional impact on adult offspring. Specifically, THC affects the development of pyramidal neurons and GABAergic interneurons via cannabinoid CB1 receptors (CB1R). However, the particular con...
Article
Full-text available
KCC2 regulates neuronal transmembrane chloride gradients and thereby controls GABA signaling in the brain. KCC2 downregulation is observed in numerous neurological and psychiatric disorders. Paradoxical, excitatory GABA signaling is usually assumed to contribute to abnormal network activity underlying the pathology. We tested this hypothesis and ex...
Article
Targeting individual neurons in vivo is a key method to study the role of single cell types within local and brain-wide microcircuits. While novel technological developments now permit assessing activity from large number of cells simultaneously, there is currently no better solution than glass micropipettes to relate the physiology and morphology...
Article
Full-text available
Lateralized Hippocampal Oscillations Underlie Distinct Aspects of Human Spatial Memory and Navigation Miller J, Watrous AJ, Tsitsiklis M, et al. Nat Commun. 2018;9(1):2423. doi:10.1038/s41467-018-04847-9. The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologic...
Article
Oscillations represent basic operational modes of the human brain. They reflect local field potential activity generated by the laminar arrangement of cell-type specific microcircuits interacting brain-wide under the influence of neuromodulators, endogenous processes and cognitive demands. Under neuropathological conditions, the spatiotemporal stru...
Article
Full-text available
The proximodistal axis is considered a major organizational principle of the hippocampus. At the interface between the hippocampus and other brain structures, CA2 apparently breaks this rule. The region is involved in social, temporal, and contextual memory function, but mechanisms remain elusive. Here, we reveal cell-type heterogeneity and a chara...
Preprint
Full-text available
The K+/Cl− co-transporter KCC2 (SLC12A5) regulates neuronal transmembrane chloride gradients and thereby controls GABA signaling in the brain. KCC2 downregulation is observed in several neurological and psychiatric disorders including epilepsy, neuropathic pain and autism spectrum disorders. Paradoxical, excitatory GABA signaling is usually assumed...
Data
Appendix S1. Behavioral CDE and CRF files. The CDE and CRF modules linked to this article can be found and downloaded as a zip folder.
Article
The brain is a complex system composed of networks of interacting elements, from genes to circuits, whose function (and dysfunction) is not derivable from the superposition of individual components. Epilepsy is frequently described as a network disease, but to date, there is no standardized framework within which network concepts applicable to all...
Article
Full-text available
The provided companion has been developed by the Behavioral Working Group of the Joint Translational Task Force of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) with the purpose of assisting the implementation of Preclinical Common Data Elements (CDE) for studying and for reporting neurobehavioral comorbid...
Preprint
Full-text available
The proximodistal axis is considered a major organizational principle of the hippocampus. Interfacing between the hippocampus and other brain systems, the CA2 region apparently breaks this rule. Apart from its specific role in social memory, CA2 has been involved in temporal and contextual memory but mechanisms remain elusive. Here, we used intrace...
Article
Understanding how the brain represents events is a fundamental question in neuroscience. The entorhinal-hippocampal system is central to such representations, which are severely compromised in some neurological diseases. In spite of much progress, a comprehensive, integrated view of spatial, temporal and other aspects of episodic representation rem...
Article
Background: Insights into human brain diseases may emerge from tissue obtained after operations on patients. However techniques requiring transduction of transgenes carried by viral vectors cannot be applied to acute human tissue. New method: We show that organotypic culture techniques can be used to maintain tissue from patients with three diff...
Article
Full-text available
KCC2 regulates neuronal transmembrane chloride gradients and thereby controls GABA signaling in the brain. KCC2 downregulation is observed in numerous neurological and psychiatric disorders. Paradoxical, excitatory GABA signaling is usually assumed to contribute to abnormal network activity underlying the pathology. We tested this hypothesis and ex...
Article
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 epil...
Article
Full-text available
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–...
Article
Full-text available
The relationship between the extracellularly measured electric field potential resulting from synaptic activity in an ensemble of neurons and intracellular signals in these neurons is an important but still open question. Based on a model neuron with a cylindrical dendrite and lumped soma, we derive a formula that substantiates a proportionality be...
Article
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...
Article
Pathological high-frequency oscillations (HFOs) (80-800 Hz) are considered biomarkers of epileptogenic tissue, but the underlying complex neuronal events are not well understood. Here, we identify and discuss several outstanding issues or conundrums in regards to the recording, analysis, and interpretation of HFOs in the epileptic brain to critical...
Article
Coherent neuronal activity in the hippocampal-entorhinal circuit is a critical mechanism for episodic memory function, which is typically impaired in temporal lobe epilepsy. To better understand how this mechanism is implemented and degraded in this condition, we used normal and epileptic rats to examine theta activity accompanying active explorati...
Article
Objective Transient high-frequency oscillations (HFOs; 150-600Hz) in local field potentials generated by human hippocampal and parahippocampal areas have been related to both physiological and pathological processes. The cellular basis and effects of normal and abnormal forms of HFOs have been controversial. This lack of agreement is clinically sig...
Article
Full-text available
The mechanisms of action of many CNS drugs have been studied extensively on the level of their target proteins, but the effects of these compounds on the level of complex CNS networks that are composed of different types of excitatory and inhibitory neurons are not well understood. Many currently used anticonvulsant drugs are known to exert potent...
Article
Full-text available
Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding th...
Article
Full-text available
Hippocampal high-frequency oscillations (HFOs) are prominent in physiological and pathological conditions. During physiological ripples (100-200 Hz), few pyramidal cells fire together coordinated by rhythmic inhibitory potentials. In the epileptic hippocampus, fast ripples (>200 Hz) reflect population spikes (PSs) from clusters of bursting cells, b...
Article
Full-text available
Episodic memory deficit is a common cognitive disorder in human temporal lobe epilepsy (TLE). However, no animal model of TLE has been shown to specifically replicate this cognitive dysfunction, which has limited its translational appeal. Here, using a task that tests for nonverbal correlates of episodic-like memory in rats, we show that kainate-tr...
Article
Full-text available
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...
Article
The hippocampus is a pivotal structure for episodic memory function. This ability relies on the possibility to integrate different features of sensory stimuli with the spatio-temporal context in which they occur. While recent studies now suggest that somatosensory information is already processed by the hippocampus, the basic mechanisms still remai...
Article
Full-text available
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 sli...
Article
Full-text available
Affective symptoms such as anxiety and depression are frequently observed in patients with epilepsy. The mechanisms of comorbidity of epilepsy and affective disorders, however, remain unclear. Diverse models are traditionally used in epilepsy research, including the status epilepticus (SE) model in rats, which are aimed at generating chronic epilep...
Article
Here, we describe new fabrication methods aimed to integrate planar tetrode-like electrodes into a polymer SU-8 based microprobe for neuronal recording applications. New concepts on the fabrication sequences are introduced in order to eliminate the typical electrode-tissue gap associated to the passivation layer. Optimization of the photolithograph...
Article
High frequency oscillations (HFO) have a variety of characteristics: band-limited or broad-band, transient burst-like phenomenon or steady-state. HFOs may be encountered under physiological or under pathological conditions (pHFO). Here we review the underlying mechanisms of oscillations, at the level of cells and networks, investigated in a variety...
Article
Full-text available
Cognitive impairment is a major concern in temporal lobe epilepsy (TLE). While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship...
Article
A major goal in epilepsy research is to understand the cellular basis of pathological forms of network oscillations, particularly those classified as high-frequency activity. What are the underlying mechanisms, and how do they arise? The topic of this review is the pattern of high-frequency oscillations that have been recorded in epileptic tissue,...
Article
Full-text available
The mechanisms involved in the transition to an epileptic seizure remain unclear. To examine them, we used tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability along with alkalinization or low Mg(2+). During the transition, distinct pre-ictal discharge...
Article
Full-text available
In rodents, cortical interneurons originate from the medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) according to precise temporal schedules. The mechanisms controlling the specification of CGE-derived interneurons and their role in cortical circuitry are still unknown. Here, we show that COUP-TFI expression becomes restricted...
Article
In rodents, cortical interneurons originate from the medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) according to precise temporal schedules. The mechanisms controlling the specification of CGE-derived interneurons and their role in cortical circuitry are still unknown. Here, we show that COUP-TFI expression becomes restricted...
Article
Full-text available
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 a...
Article
Full-text available
This paper presents novel design, fabrication, packaging and the first in vitro neural activity recordings of SU-8-based microneedles. The polymer SU-8 was chosen because it provides excellent features for the fabrication of flexible and thin probes. A microprobe was designed in order to allow a clean insertion and to minimize the damage caused to...
Article
Drug-resistant temporal lobe epilepsy (TLE) can be treated by tailored surgery guided by electrocorticography (ECoG). Although its value is still controversial, ECoG activity can provide continuous information on intracortical interactions that may be useful to understand the pathophysiology of TLE. The goal of this study is to characterize local i...
Article
Ripples are sharp-wave-associated field oscillations (100-300 Hz) recorded in the hippocampus during behavioral immobility and slow-wave sleep. In epileptic rats and humans, a different and faster oscillation (200-600 Hz), termed fast ripples, has been described. However, the basic mechanisms are unknown. Here, we propose that fast ripples emerge f...
Article
We introduce a monopole model to examine the sources of ictal and interictal activity in mesial temporal lobe epilepsy (MTLE) recorded using foramen ovale electrodes (FOE). Classical electrostatic theory was applied to derive mathematical expressions. Interictal and ictal activity was acquired using FOE and scalp video-electroencephalography (v-EEG...
Article
The subiculum has a strategic position in controlling hippocampal activity and is now receiving much experimental attention. However, information regarding this structure remains fragmented and there are important gaps in our knowledge between what we know about the subicular architecture and its biological function. In recent years a substantial a...
Article
The subiculum has long been considered as a simple bidirectional relay region interposed between the hippocampus and the temporal cortex. Recent evidence, however, suggests that this region has specific roles in the cognitive functions and pathological deficits of the hippocampal formation. A group of 20 researchers participated in an ESF-sponsored...
Article
Full-text available
Temporal lobe epilepsy (TLE) is the most frequent form of pharmaco-resistant epilepsy in human. Research using material from TLE patients undergoing surgery and animal models has significantly increased in the last decade. We review recent findings obtained over the last years from electrophysiological and anatomical studies in human and animal mod...
Article
Hippocampal population discharges such as sharp waves, epileptiform firing, and GDPs recur at long and variable intervals. The mechanisms for their precise timing are not well understood. Here, we show that population bursts in the disinhibited CA3 region are initiated at a threshold level of population firing after recovery from a previous event....
Article
Full-text available
The subiculum, which has a strategic position in controlling hippocampal activity, is receiving significant attention in epilepsy research. However, the functional organization of subicular circuits remains unknown. Here, we combined different recording and analytical methods to study focal and widespread population activity in the isolated subicul...
Article
Full-text available
The subiculum, which provides the major hippocampal output, contains different cell types including weak/strong bursting and regular-spiking cells, and fast-spiking interneurons. These cellular populations play different roles in the generation of physiological rhythms and epileptiform activity. However, their intrinsic connectivity and the synapti...
Article
We combined whole-cell recordings with Neurobiotin labeling to examine the electrophysiological and morphological properties of neurons from the ventral subicular complex in vitro (including the subicular, presubicular, and parasubicular areas). No a priori morphological sampling criteria were used to select cells. Cells were classified as bursting...