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All-Optical Dissection of Hippocampal Circuits Using Voltage Imaging

Objective

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.

Call for proposal

ERC-2020-STG
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Funding Scheme

ERC-STG - Starting Grant

Host institution

THE HEBREW UNIVERSITY OF JERUSALEM
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 486 797

Beneficiaries (1)

THE HEBREW UNIVERSITY OF JERUSALEM
Israel
EU contribution
€ 1 486 797
Address
Edmond J Safra Campus Givat Ram
91904 Jerusalem
Activity type
Higher or Secondary Education Establishments