Interrogation of multiplexed subicular output to cortical and subcortical structures

• Applicant: Dr. Noam Nitzan
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451007688

The hippocampus is a brain structure critical for episodic memory and spatial navigation. Damage to the hippocampus results in severe anterograde amnesia for explicit memory, while leaving implicit memory intact. It is also among the first areas to be affected by Alzheimer’s disease, a devastating, irreversible brain atrophy, which progressively impairs cognitive functions. Current work investigating hippocampal output examines how information processed by the hippocampus is transmitted back to the neocortex. However, approximately the same number of hippocampal output fibers target subcortical structures and the significance as well as physiological relevance of these outputs are much less investigated. A major subcortical hippocampal target that remains largely under-investigated are the mammillary bodies (MBs), which will be a major focus of my work. The MBs are known to be of a particular clinical relevance for memory due to their involvement in various forms of anterograde amnesia including Korsakoff’s syndrome and diencephalic amnesia, as well as in Alzheimer’s disease. However, the actual computations performed by this structure and how they contribute to memory are not well understood, largely due to the paucity of studies where MBs activity was directly monitored during behavior. A second focus of this work will be the retrosplenial cortex (RSC), a cortical hub at the interface between the hippocampus and the neocortex that is also heavily implicated in memory functions. Both the MBs and the RSC are targeted by different collaterals of the same hippocampal output neurons in the subiculum, indicating that the same information is routed in cortical and subcortical directions. However, the importance of such a wiring scheme is unknown. In the work proposed here, we will investigate how upstream information conveyed by the subiculum is read-out by the MBs and RSC. We will focus on two prominent hippocampal patterns that can be conveyed by this pathway: theta oscillations and sharp-wave ripples with the overall objective of gaining insights about the factors that determine how neural information sent by an upstream structure is transformed by its downstream readers. We hope that the proposed research will help us gain important insights not only onto the processes underlying memory functions and how they coordinate across brain structures, but also onto the fundamental principles underlying the input-output transfer of spiking information.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Gyorgy Buzsaki, Ph.D.