The cellular landscape of the living human hippocampus in health and disease

• Applicant: Larissa Kraus
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 444112617

• Final Report Year: 2023

Final Report Abstract

Epilepsy is a devastating disease affecting 1 million people worldwide. Every third patient suffering from epilepsy does not respond to medication and continues to suffer from frequent seizures. There is an urgent need to better understand epileptic mechanisms in the human brain so we can develop effective treatment options and help patients. Thus, this project takes an innovative approach, utilizing resected living human brain tissue to directly investigate the static organization and dynamic functioning of the epileptic human brain. I use cutting-edge single-cell spatial transcriptomics to label up to 400 RNA targets in a single sample to investigate the cellular-molecular organization of the human brain in epilepsy. In this way, I have begun to show diverse cell types within the human hippocampus, a region most affected in temporal lobe epilepsy. I have also been able to show region-specific and epilepsy-related in the epileptic hippocampus. In addition, I have begun to unravel the function of specific types of neurons in seizure generation and maintenance in the human brain. This research aims to provide profound insights into the changes occurring in the human brain region in epilepsy, potentially paving the way for novel approaches in drug development. The significance of my research extends far beyond epilepsy. Future findings could not only bring much-needed advancements in epilepsy treatment but also offer fundamental insights into how the healthy human brain functions, ultimately enhancing the lives of individuals with a variety of neurological disorders.

Publications

• Functional and molecular architecture of cell types in the living human cortex. FENS Forum, Paris, France (2022).
  Larissa Kraus
  
• Functional and molecular architecture of the healthy and diseased brain. 15th Annual Canadian Neuroscience Meeting, Toronto, Canada (2022).
  Larissa Kraus
  
• The cellular-molecular landscape of the living human brain in epilepsy. 16th Annual Canadian Neuroscience Meeting, Montreal, Canada (2023).
  Larissa Kraus