Glutamate induces de novo growth of functional spines in developing cortex
Open accessAbstract
Mature cortical pyramidal neurons receive excitatory inputs onto small protrusions emanating from their dendrites called spines. Spines undergo activity-dependent remodelling, stabilization and pruning during development, and similar structural changes can be triggered by learning and changes in sensory experiences. However, the biochemical triggers and mechanisms of de novo spine formation in the developing brain and the functional significance of new spines to neuronal connectivity are largely unknown. Here we develop an approach to induce and monitor de novo spine formation in real time using combined two-photon laser-scanning microscopy and two-photon laser uncaging of glutamate. Our data demonstrate that, in mouse cortical layer 2/3 pyramidal neurons, glutamate is sufficient to trigger de novo spine growth from the dendrite shaft in a location-specific manner. We find that glutamate-induced spinogenesis requires opening of NMDARs (N-methyl-D-aspartate-type glutamate receptors) and activation of protein kinase A (PKA) but is independent of calcium-calmodulin-dependent kinase II (CaMKII) and tyrosine kinase receptor B (TrkB) receptors. Furthermore, newly formed spines express glutamate receptors and are rapidly functional such that they transduce presynaptic activity into postsynaptic signals. Together, our data demonstrate that early neural connectivity is shaped by activity in a spatially precise manner and that nascent dendrite spines are rapidly functionally incorporated into cortical circuits.
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These findings raise the possibility that the mechanism by which the postsynaptic membrane expands with spine growth in response to glutamate receptor activation may resemble the Ral/exocyst pathway by which the glutamatergic synapse at the fly NMJ expands its postsynaptic membrane.
“These findings raise the possibility that the mechanism by which the postsynaptic membrane expands with spine growth in response to glutamate receptor activation (Kwon and Sabatini, 2011) may resemble the Ral/exocyst pathway by which the glutamatergic synapse at the fly NMJ expands its postsynaptic membrane.”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Kwon and Sabatini, 2011
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- Authors
- Kwon, H.-B., & Sabatini, B. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sabatini, Bernardo L.
- Venue
- Nature
- Published
- 2011-05-08
- Volume
- 474
- Issue
- 7349
- Pages
- 100-104
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3107907
- OpenAlex
- W2060584787
- Cited by
- 368
- References
- 7
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 14 · 2023: 18 · 2022: 22 · 2021: 38 · 2020: 25 · 2019: 19 · 2018: 17 · 2017: 37 · 2016: 27 · 2015: 27 · 2014: 35 · 2013: 22 · 2012: 33
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Simons Foundation
- Simons Foundation Autism Research Initiative
- National Institute of Neurological Disorders and Stroke (R01NS046579, NS046579)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, glutamate, NMDA receptor, protein kinase A, spine maturation, presynaptic activity, glutamate uncaging, neural circuit development
- MeSH terms
- Animals, Calcium, Cerebral Cortex, Electric Stimulation, Mice, Inbred C57BL, Pyramidal Cells, Neurotransmitter Agents, Glutamic Acid, Dendritic Spines, Mice
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