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

Understanding the operations of neurons in the human brain is a key component for the development of therapies for disorders such as epilepsy, depression and brain tumours. The scientific community has primarily gained knowledge of basic operations of the human brain from studying cell cultures or animal models. However, for both basic scientific and therapeutic applications, it is of utmost importance to investigate these mechanisms directly from the human brain.Here, using living resected brain tissue from patients suffering from epilepsy or brain tumours, we aim to identify unresolved cellular properties of the human brain using cutting-edge techniques, such as single cell RNA-sequencing, single-molecule fluorescent in situ hybridization and electrophysiological approaches. These techniques will enable us to identify novel neuronal subpopulations and develop tools for cell-type-specific genetic manipulation. Our goal is to use these methods to identify the cell-type organization of the human hippocampus, and observe the function of PV and SST interneurons in seizure generation and maintenance. Leveraging this cellular-resolved understanding, we plan to identify new potential mechanisms involved in epilepsy and develop novel therapeutic targets and strategies.In summary, our approach will help to delineate the heterogeneity of neuronal subpopulations and enable us to understand the participation of interneuron subtypes in epileptic activity within the living human brain. Our research will provide unprecedented knowledge on cell-type-specific gene expression and functional involvement of neuronal subtypes in physiological and pathological operations of the living human brain.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Mark Steven Cembrowski, Ph.D.