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Mathematical Modeling of Adult Neurogenesis

Learning and cognition require lifelong formation of neurons. Formation of neurons in the adult is referred to as adult neurogenesis. It is driven by a small population of neural stem cells. Mathematical models help to quantify neural stem cell properties and their change during aging.

Cooperation partners: F. Ziebell (EMBL Heidelberg), G. Kalamakis (Department of Biosystems Science and Engineering, ETH Z├╝rich), A. Martin-Villalba (German Cancer Research Center dkfz, Heidelberg), A. Marciniak-Czochra (Institute for Applied Mathematics, Heidelberg University)

In the adult murine brain neural stem cells (NSC) are located in the hippocampus and in the subventricular zone. Experiments indicate that the total number of NSC and the number of actively dividing NSC decline with age. However, the decline saturates at old ages and complete extinction of NSC is prevented. Ordinary differential equation models allow to study the mechanisms underlying these changes. The models suggest that an age-related reduction of the rates at which quiescent cells are activated can explain the observed changes. Changes of cell-cycle duration or self-renewal are not in line with the measured dynamics.

Key publications

  1. L. Harris, P. Rigo, T. Stiehl, Z. Gaber, S. H. L. Austin, M. del Mar Masdeu, A. Edwards, N. Urban, A. Marciniak-Czochra, F. Guillemot. "Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis." Cell Stem Cell, 2021, doi: 10.1016/j.stem.2021.01.003.
  2. LPM. Kremer*, S. Cerrizuela*, S. Dehler**, T. Stiehl**, J. Weinmann, H. Abendroth, S. Kleber, A. Laure, J. El Andari, S. Anders, A. Marciniak-Czochra, D. Grimm, A. Martin-Villalba. "High throughput screening of novel AAV capsids identifies variants for transduction of adult NSCs within the subventricular zone." Mol. Ther. Methods Clin. Dev. 23:33-50, 2021. * shared first authorship, ** shared second authorship.
  3. G. Kalamakis, D. Brune, S. Ravichandran, J. Bolz, W. Fan, F. Ziebell, T. Stiehl, F. Catala-Martinez, J. Kupke, S. Zhao, E. Llorens-Bobadilla, K. Bauer, S. Limpert, B. Berger, U. Christen, P. Schmezer, J.P. Mallm, B. Berninger, S. Anders, A. Del Sol, A. Marciniak-Czochra, and A. Martin-Villalba. "Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain", Cell, 176(6):1407-1419.e14, 2019.