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Functional convergence of developmentally and adult‐generated granule cells in dentate gyrus circuits supporting hippocampus‐dependent memory
Authors:Kirill Zaslavsky  Anne L. Wheeler  Alonso Martinez‐Canabal  Afra H. Wang  Masanori Sakaguchi  Andres M. Lozano  Paul W. Frankland
Affiliation:1. Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8;2. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, M5S 1A8;3. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada, M5G 1X8;4. Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada, M5T 2S8;5. Department of Physiology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8
Abstract:
In the hippocampus, the production of dentate granule cells (DGCs) persists into adulthood. As adult‐generated neurons are thought to contribute to hippocampal memory processing, promoting adult neurogenesis therefore offers the potential for restoring mnemonic function in the aged or diseased brain. Within this regenerative context, one key issue is whether developmentally generated and adult‐generated DGCs represent functionally equivalent or distinct neuronal populations. To address this, we labeled separate cohorts of developmentally generated and adult‐generated DGCs and used immunohistochemical approaches to compare their integration into circuits supporting hippocampus‐dependent memory in intact mice. First, in the water maze task, rates of integration of adult‐generated DGCs were regulated by maturation, with maximal integration not occurring until DGCs were five or more weeks in age. Second, these rates of integration were equivalent for embryonically, postnatally, and adult‐generated DGCs. Third, these findings generalized to another hippocampus‐dependent task, contextual fear conditioning. Together, these experiments indicate that developmentally generated and adult‐generated DGCs are integrated into hippocampal memory networks at similar rates, and suggest a functional equivalence between DGCs generated at different developmental stages. © 2010 Wiley Periodicals, Inc.
Keywords:neurogenesis  contextual fear conditioning  Morris water maze  learning  mice
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