Descripción del proyecto
Obtención de imágenes del potencial para estudiar el procesamiento de la información espacial por parte del hipocampo
El hipocampo desempeña un papel fundamental en el almacenamiento de recuerdos episódicos y ha sido estudiado por su importancia en la memoria espacial. Además, es un modelo importante para los estudios «in vitro» sobre las bases moleculares, celulares y de microcircuitos del aprendizaje y la memoria. El proyecto AllOptHIPP, financiado con fondos europeos, aplicará tecnologías nuevas para registrar y manipular simultáneamente el potencial de membrana de múltiples neuronas en ratones a fin de estudiar los mecanismos de procesamiento de la información espacial del hipocampo. La investigación acortará la brecha entre los estudios mecanicistas «in vitro» y la descripción «in vivo» de las representaciones espaciales para proporcionar información específica sobre la base mecanicista de la memoria espacial como primer paso hacia una mayor comprensión sobre la forma en que el encéfalo almacena y recupera los recuerdos episódicos.
Objetivo
The hippocampus is critical for the storage of episodic memories and has been extensively studied on its role in spatial memory. The hippocampus is also a central model for in vitro studies on the molecular, cellular and microcircuit basis for learning and memory. I propose to use a new technology that I developed to record and manipulate the membrane potential of multiple neurons, simultaneously, in behaving animals to reveal the mechanisms by which hippocampal circuits process spatial information. This research will bridge the gap between the in vitro mechanistic studies and the in vivo efforts to describe the spatial representations.
I first propose to employ the voltage imaging technology for detailed mechanistic studies of the function and plasticity of hippocampal microcircuits during place cell formation (Objective 1). To this end, we will combine voltage imaging with Optogenetics in head-fixed mice performing virtual navigation in familiar and novel environments. To expand to a ‘systems’ view on hippocampal plasticity, we will next establish a method for optical selection of single neurons based on their functional profile (Objective 2). We will use this technology to trace the long-range projections and the pre- and postsynaptic landscape of photo-selected CA1 neurons. In the last objective, we will combine both technologies to dissect the contribution of different entorhinal cell types (i.e. grid cells, border cells, and speed cells) to place cell formation in CA1 (objective 3). To this end, we will image the entorhinal cortex and photo-select cells based on their functional profiles. We will then image CA1 while manipulating the activity of the selected entorhinal cells. Our work will provide new discoveries on the mechanistic basis for spatial memory and will comprise a first step towards broader understanding of how the brain stores and retrieves episodic memories.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
91904 Jerusalem
Israel