Instituto Cajal
Instituto Cajal
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Dissecting subcircuits underlying hippocampal function
Liset M de la Prida is a Physicist (1994) and PhD in Neuroscience (1998), who leads the Laboratorio de Circuitos Neuronales at the Instituto Cajal, Madrid, Spain (http://www.hippo-circuitlab.es). The main focus of her lab is to understand the function of the hippocampal circuits in the normal and the diseased brain, in particular oscillations and neuronal representations. She is a leading international expert in the study of the basic mechanisms of physiological ripples and epileptic fast ripples, with strong visibility as developer of novel groundbreaking electrophysiological tools. Dr. de la Prida serves as an Editor for prestigious journals including eLife, Journal of Neuroscience Methods and eNeuro, and has commissioning duties in the American Epilepsy Society, FENS and the Spanish Society for Neurosciences.
What is hippocampal sclerosis? A cell-type specific perspective
Temporal lobe epilepsy is considered a neuronal microcircuit dysfunction, yet mechanisms are poorly understood. Here we will discuss recent data on cell-type specific alterations of hippocampal microcircuit function in experimental models of temporal lobe epilepsy. We will highlight the importance of leveraging on cellular heterogeneity to better understand the complexities accompanying hippocampal sclerosis.
Using evolutionary algorithms to explore single-cell heterogeneity and microcircuit operation in the hippocampus
The hippocampus-entorhinal system is critical for learning and memory. Recent cutting-edge single-cell technologies from RNAseq to electrophysiology are disclosing a so far unrecognized heterogeneity within the major cell types (1). Surprisingly, massive high-throughput recordings of these very same cells identify low dimensional microcircuit dynamics (2,3). Reconciling both views is critical to understand how the brain operates. " "The CA1 region is considered high in the hierarchy of the entorhinal-hippocampal system. Traditionally viewed as a single layered structure, recent evidence has disclosed an exquisite laminar organization across deep and superficial pyramidal sublayers at the transcriptional, morphological and functional levels (1,4,5). Such a low-dimensional segregation may be driven by a combination of intrinsic, biophysical and microcircuit factors but mechanisms are unknown." "Here, we exploit evolutionary algorithms to address the effect of single-cell heterogeneity on CA1 pyramidal cell activity (6). First, we developed a biophysically realistic model of CA1 pyramidal cells using the Hodgkin-Huxley multi-compartment formalism in the Neuron+Python platform and the morphological database Neuromorpho.org. We adopted genetic algorithms (GA) to identify passive, active and synaptic conductances resulting in realistic electrophysiological behavior. We then used the generated models to explore the functional effect of intrinsic, synaptic and morphological heterogeneity during oscillatory activities. By combining results from all simulations in a logistic regression model we evaluated the effect of up/down-regulation of different factors. We found that muyltidimensional excitatory and inhibitory inputs interact with morphological and intrinsic factors to determine a low dimensional subset of output features (e.g. phase-locking preference) that matches non-fitted experimental data.
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