A role for primary cilia in glutamatergic synaptic integration of adult-born neurons.
The sequential synaptic integration of adult-born neurons has been widely examined in rodents, but the mechanisms regulating the integration remain largely unknown. The primary cilium, a microtubule-based signaling center, is essential for vertebrate development, including the development of the CNS. We examined the assembly and function of the primary cilium in the synaptic integration of adult-born mouse hippocampal neurons. Primary cilia were absent in young adult-born neurons, but assembled precisely at the stage when newborn neurons approach their final destination, further extend dendrites and form synapses with entorhinal cortical projections. Conditional deletion of cilia from adult-born neurons induced severe defects in dendritic refinement and synapse formation. Deletion of primary cilia led to enhanced Wnt and β-catenin signaling, which may account for these developmental defects. Taken together, our findings identify the assembly of primary cilia as a critical regulatory event in the dendritic refinement and synaptic integration of adult-born neurons.
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York, USA.
Natsuko
N
Kumamoto
Yan
Y
Gu
Jia
J
Wang
Stephen
S
Janoschka
Ken-Ichi
K
Takemaru
Joel
J
Levine
Shaoyu
S
Ge
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D002923:Cilia / Q000502:physiology*; D003712:Dendrites / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D018698:Glutamic Acid / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques; D037121:Plant Lectins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D002135:Calcium-Binding Proteins; C486352:Cetn3 protein, mouse; D000075402:Channelrhodopsins; C490202:Kif3a protein, mouse; D037121:Plant Lectins; D034741:RNA, Small Interfering; D051176:beta Catenin; C034981:tomato lectin; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001616:beta-Galactosidase; D016547:Kinesins; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3