Structural and functional plasticity in hippocampal networks of the young and aged brain

• Applicant: Dr. Gregor-Alexander Pilz
• Subject Area: Experimental and Theoretical Network Neuroscience ; Developmental Neurobiology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 466396759

The dentate gyrus (DG) of the hippocampus harbors neural stem cells (NSCs) which give rise to granule cells throughout life. During this process termed adult neurogenesis adult-born neurons migrate, mature and integrate into the preexisting circuitry of the hippocampus. Adult-born neurons play a functional role in certain forms of learning and memory and levels of adult neurogenesis are altered in various neuropsychiatric diseases. A complete picture of the dynamic process of adult neurogenesis required the establishment of a technique to observe cellular lineages from NSC division to functional integration in a continuous fashion. Chronic in vivo 2 Photon imaging through a transcortical window allowed for a detailed characterization of NSC lineages as well as for measurements of neural activity in granule cells of an awake behaving animal. However, open questions on how adult-born neurons mature, integrate and in consequence alter network function in the hippocampus during behavior remain. Therefore, I will address three fundamental questions of adult neurogenesis and hippocampal function.The morphological and functional requirements for successful integration of immature neurons will be uncovered by chronic imaging over the time course of weeks after cell birth. How candidate molecular factors and physiological interventions promote maturation and integration will be tested in addition with the aim to enhance effectiveness of adult neurogenesis. Over the course of maturation and during integration adultborn neurons possess unique physiological properties and exert specific functions in the hippocampal circuit. How adult-born neurons impact information processing and memory formation in the DG – CA3 (cornuamonis region 3) circuit over the course of their integration will be investigated by direct observation of neuronal populations and simultaneous manipulation of adult-born granule cell activity. This functional testing will be carried out in a DG specific behavioral pattern separation task. Chronological aging often coincides with difficulties in the formation and retrieval of new memories. The levels of adult neurogenesis have been shown to decrease with advancing age in mammalian species. Which functional contribution lower numbers of adult generated play in hippocampal function and memory formation in aged animals remains unknown and will be addressed by a direct and chronic observational approach. If enhancing the levels of adult neurogenesis in the aged brain improves network function and memory formation will be probed by a diverse set of physiological interventions. By following these scientific aims, a more complete picture of the specific role for adult neurogenesis in function of the hippocampus will emerge.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Miniature Microscope for In Vivo
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)