Laboratorio de Circuitos Neuronales

We use next generation high-density probes to record oscillations from different hippocampal layers and brain regions during execution of simple memory tasks. Our aim is to evaluate how function and dysfunction of natural brain rhythms relate to memory processes.

Hippocampal activity in health and disease

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 generated with a special emphasis in the cellular and synaptic rules that govern circuit dynamics. To tackle these questions we exploit modern techniques for selective interrogation of neuronal circuits with high-density arrays coupled to cell-type specific opto and chemogenetics. We combine electrophysiological tools with behavioral assessments to relate microcircuit function and dysfunction with cognition. We focus in different forms of activity, including several types of oscillations (ripples, fast ripples, theta and gamma) and epileptiform events.

Unsupervised segregation of neurophysiological events using UMAP (Uniform Manifold Approximation and Projection) for dimensionality reduction

Machine learning

We use machine learning tools to analyze neurophysiological and behavioral signals obtained with high-density probes and high-speed/resolution cameras. With supervised learning, we train models of known input and output data to predict behaviour. With unsupervised learning, we aim to discover hidden patterns on neurophysiological signals. We exploit our unique computational resources and get access to supercomputers for high speed performance.

The CA1 stratum pyramidale of the dorsal hippocampus can be differentiated into deep and superficial sub-layers on the basis of cell density, gene and protein expression, shape and function of pyramidal cells and how are they innervated by local circuit interneurons. Such a deep-superficial subcircuit structure should have profound impact in hippocampal function.

Mapping hippocampal microcircuits

Hippocampal operation has been traditionally viewed from the tri-synaptic microcircuit perspective. Following our recent discovery of a functional regionalization of CA1 pyramidal cell activity during hippocampal ripples in deep and superficial CA1 sublayers (Valero et al. Nat Neu 2015), we aim to understand the neurophysiological basis and cognitive implications. We are now embarked in better understading how deep and superficial sublayers operate and what different role they play in cognition.

Slices are prepared from resected brain areas, including hippocampus and neocortex. This material is unique to better understand the functional organization of the human brain. We record electrical activity from single cells and microcircuits ex vivo and combine cutting edge genetic and molecular techniques.

Understanding diseases of the human brain

We aim to translate our research to the human brain in collaboration with our clinical partners in Paris and Madrid. We use in vivo and in vitro electrophysiological and imaging approaches, that we combine with immunostaining studies and gene expression analysis to identify different neuronal populations in the human hippocampus. Our purpose is to better understand the epileptic condition and to identify new therapeutic approaches.