Functional convergence of developmentally and adult-generated granule cells in dentate gyrus circuits supporting hippocampus-dependent memory.
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.
Stone
Scellig S D
SS
Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada.
Teixeira
Cátia M
CM
Zaslavsky
Kirill
K
Wheeler
Anne L
AL
Martinez-Canabal
Alonso
A
Wang
Afra H
AH
Sakaguchi
Masanori
M
Lozano
Andres M
AM
Frankland
Paul W
PW
D000367:Age Factors; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003214:Conditioning, Classical; D003292:Convulsants / Q000633:toxicity; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology* / Q000254:growth & development / Q000473:pathology; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000502:physiology; D005239:Fear / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D055495:Neurogenesis; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010433:Pentylenetetrazole / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D003292:Convulsants; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C092069:activity regulated cytoskeletal-associated protein; D010433:Pentylenetetrazole