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The cell-type-specific organization and operation of the living human subiculum in health and epilepsy

Principal Investigator:
  • Mark Cembrowski, University of British Columbia
  • The Azrieli Foundation

Project Overview

The hippocampus is a brain region critical for learning, memory, spatial navigation and emotion. The main output of the hippocampus is termed the “subiculum”, and is responsible delivering hippocampal output to a host of other brain regions. As such, the subiculum is powerfully situated to brain activity in healthy conditions, and may be prominently involved in disorders like epilepsy. Despite this, to date there is little knowledge of the precise organization or operation of the human subiculum, either in health or illness.

In this project, Dr. Cembrowski will obtain living subiculum brain tissue from consenting participants undergoing resective surgery for epilepsy. This tissue, encompassing both healthy and dysregulated subiculum regions, will be examined using cutting-edge neuroscience technologies and “Big Data” analysis. This methodology will provide unprecedented insight into the precise organization and operation of the living human subiculum. They will measure the expression of every gene in the mouse genome for thousands of individual subiculum neurons. From these Big Data, they will map genes and neuron types that may be critical and unique for human subiculum function, and record the electrical activity of these cells types. The ultimate aim of this research is to generate a rigorous understanding of the organization of the living human subiculum, in both health and epilepsy.

In the short term, the research will provide a comprehensive understanding of the fundamental biology of the human subiculum, help to understand mechanisms of epilepsy, and develop new drug targets for future therapeutic use. In the long term, the research will form a framework for interpreting the precise cellular and molecular manifestations of subiculum disorder and disease.