The mossy fiber synapse - imprinting a memory trace in CA3

• Applicant: Dr. Thomas Hainmueller
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427309605

Memories about the events of our lives are a fundamental basis for our thinking and personality. Loss or alterations in the ability to remember such episodes, frequently observed in dementia or depression, are devastating for those affected. Nevertheless, the mechanisms of storage and retrieval of episodic memories are poorly understood. The hippocampus is a brain area essential for this process. According to current theories, the highly interconnected network of the hippocampal CA3 subfield stores associations between individual elements of memories encoded by cortical neurons projecting to the hippocampus. Furthermore, CA3 receives synaptic inputs from granule cells in the dentate gyrus, another hippocampal area. These inputs are critical for storing memories, but often dispensable for memory recall. However, the changes in synaptic connectivity and activity patterns in CA3 required for memory storage and the role of granule cells in that process remain enigmatic. The aim of the proposed project is thus to acquire simultaneous high-density electrophysiological recordings from dentate gyrus and CA3 neurons in mice performing a spatial memory task. We will observe their memory-related firing activity and detect synaptically connected pairs of granule cells and their postsynaptic targets to determine the impact of granule cell activity on memory encoding, consolidation and retrieval. Furthermore, we will use optogenetic manipulations to identify the role of granule cell activity on memory-related neuronal network functions and behavior. The proposed experiments will yield substantial advances in our understanding of memory-mechanisms, which are indispensable prerequisites for the future development of potential therapies for memory disorders.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Gyorgy Buzsaki, Ph.D.