A role for primary cilia in glutamatergic synaptic integration of adult-born neurons
Open accessAbstract
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.
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Primary cilia length plays a critical role in the proper formation and function of synapses, which is an important pathological feature of AD.
“Collectively, these findings underscore the critical role of primary cilia length in the proper formation and function of synapses, which is an important pathological feature of AD.”
From Changes of the Primary Cilia in Alzheimer's Disease Pathogenesis (2025) · cites this paper as Kumamoto et al. 2012
The Discussion (“Essential roles of primary cilia in neuronal development”; page unavailable) reports that deleting primary cilia from newborn hippocampal neurons disrupted synaptic integration and reduced synaptic-event frequency. It does not establish that cilia length, specifically, controls synapse formation or function, and it does not connect these findings to Alzheimer’s disease. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPrimary cilia are of vital importance for neuronal synaptogenesis.
“Primary cilia are also of vital importance for neuronal synaptogenesis.Defects in primary cilia can lead to reduced neuronal dendrite length and prevent neurons from being properly integrated into neural circuits (Kumamoto et al. 2012).”
From Changes of the Primary Cilia in Alzheimer's Disease Pathogenesis (2025) · cites this paper as Kumamoto et al. 2012
The Results report shorter dendrites and reduced synaptic input after cilia disruption in adult-born dentate granule cells; the Discussion describes severely disrupted integration with entorhinal projections. This supports an important role for cilia in that specific setting, but the unqualified claim about neuronal synaptogenesis generally extends beyond what the paper establishes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredProper cilia assembly is necessary for the formation of glutamatergic synapses with entorhinal cortical projections in newborn dentate granule cells of 5-week-old female C57 mice.
“Additionally, proper cilia assembly is necessary for the formation of glutamatergic synapses with entorhinal cortical projections, as demonstrated by Kumamoto et al. in newborn dentate granule cells of 5-week-old female C57 mice (Kumamoto et al., 2012).”
From Primary cilia in the mature brain: emerging roles in Alzheimer's disease pathogenesis (2025) · cites this paper as Kumamoto et al., 2012
Defects in primary cilia can lead to reduced neuronal dendrite length and prevent neurons from being properly integrated into neural circuits.
“Primary cilia are also of vital importance for neuronal synaptogenesis.Defects in primary cilia can lead to reduced neuronal dendrite length and prevent neurons from being properly integrated into neural circuits (Kumamoto et al. 2012).”
From Changes of the Primary Cilia in Alzheimer's Disease Pathogenesis (2025) · cites this paper as Kumamoto et al. 2012
Primary cilia are key regulators of autophagy-endolysosomal pathways, and when ciliary-autophagic trafficking is disturbed, ciliary cargo can be redirected toward extracellular vesicle secretion.
“Furthermore, PC are key regulators of autophagy-endolysosomal pathways, and when ciliary-autophagic trafficking is disturbed, ciliary cargo can be redirected toward EV secretion [102,103,104].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [104]
The Introduction and Discussion describe primary cilia in neuronal signaling and synaptic integration, not autophagy or extracellular vesicle secretion. The Results section on primary ciliogenesis examines endosome/lysosome trafficking but does not connect it to ciliary-autophagic trafficking or redirection of ciliary cargo. Searches for those terms found no passage addressing the attributed claim. (LLM, conf=0.76)
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Self-citation
- Authors
- Kumamoto, N., Gu, Y., Wang, J., Janoschka, S., Takemaru, K.-I., Levine, J., & Ge, S.
- Affiliations
- State University of New York (US)
- Stony Brook University (US)
- Corresponding author
- Ge, Shaoyu
- Venue
- Nature Neuroscience
- Published
- 2012-02-05
- Volume
- 15
- Issue
- 3
- Pages
- 399-405
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3288565
- OpenAlex
- W2029000592
- Cited by
- 196
- References
- 52
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 12 · 2023: 8 · 2022: 8 · 2021: 14 · 2020: 25 · 2019: 10 · 2018: 5 · 2017: 18 · 2016: 15 · 2015: 13 · 2014: 16 · 2013: 14 · 2012: 14
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL107493, R56HL107493, R01HL107493)
- National Institute of Neurological Disorders and Stroke (R01NS065915, NS065915)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- primary cilia, adult neurogenesis, hippocampal neurons, synaptic integration, dendritic refinement, synaptogenesis, entorhinal cortex, Wnt signaling, β-catenin signaling, glutamatergic synapses
- MeSH terms
- Channelrhodopsins, Adenylyl Cyclases, Analysis of Variance, Animals, beta-Galactosidase, Calcium-Binding Proteins, Cilia, Dendrites, Female, Ganglia, Spinal, Male, Mice, Transgenic, Neurons, Synapses, Time Factors, Transfection, Signal Transduction, Kinesins, Patch-Clamp Techniques, Microscopy, Confocal, Glutamic Acid, 6-Cyano-7-nitroquinoxaline-2,3-dione, Excitatory Postsynaptic Potentials, RNA, Small Interfering, Plant Lectins, beta Catenin, Mice, Neurogenesis
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