Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus

Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and t...

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Bibliographic Details
Published in:PLoS biology 2008-11, Vol.6 (11), p.e272-e272
Main Authors: Jessberger, Sebastian, Aigner, Stefan, Clemenson, Jr, Gregory D, Toni, Nicolas, Lie, D Chichung, Karalay, Ozlem, Overall, Rupert, Kempermann, Gerd, Gage, Fred H
Format: Article
Language:English
Subjects:
Adult Stem Cells - cytology
Animals
Cell Differentiation
Cyclin-Dependent Kinase 5 - genetics
Cyclin-Dependent Kinase 5 - metabolism
Dendrites - physiology
Dentate Gyrus - cytology
Disease
Female
Gene Expression Regulation, Developmental
Gene loci
Hippocampus - cytology
Humans
Medical research
Mice
Mice, Inbred C57BL
Migration
Neurogenesis
Neurons
Neurons - cytology
Neurons - physiology
Neuroscience
Proteins
Rats
Retroviridae - genetics
Rodents
Stem cells
Synapses - physiology
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Summary:Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5) activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.0060272