Essential Role of Presynaptic NMDA Receptors in Activity-Dependent BDNF Secretion and Corticostriatal LTP
Open accessAbstract
Activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) in postsynaptic dendrites is required for long-term potentiation (LTP) of many excitatory synapses, but the role of presynaptic axonal NMDARs in synaptic plasticity remains to be clarified. Here we report that axonal NMDARs play an essential role in LTP induction at mouse corticostriatal synapses by triggering activity-induced presynaptic secretion of brain-derived neurotrophic factor (BDNF). Genetic depletion of either BDNF or the NMDAR subunit GluN1 specifically in cortical axons abolished corticostriatal LTP in response to theta burst stimulation (TBS). Furthermore, functional axonal NMDARs were required for TBS-triggered prolonged axonal Ca(2+) elevation and BDNF secretion, supporting the notion that activation of axonal NMDARs induces BDNF secretion via enhancing Ca(2+) signals in the presynaptic nerve terminals. These results demonstrate that presynaptic NMDARs are equally important as postsynaptic NMDARs in LTP induction of corticostriatal synapses due to their role in mediating activity-induced presynaptic BDNF secretion.
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Execution of motor behavior is controlled by top-down projections from cortical areas to the dorsal striatum, which form strong excitatory synaptic connections onto striatal output neurons.
“The execution of motor behavior is controlled by top-down projections from cortical areas to the dorsal striatum (caudate putamen in primates), which form strong excitatory synaptic connections onto striatal output neurons [3][4][5].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [3]
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- Authors
- Park, H., Popescu, A., & Poo, M.-M.
- Affiliations
- University of California, Berkeley (US)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Poo, Mu-ming
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 84
- Issue
- 5
- Pages
- 1009-1022
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4465395
- OpenAlex
- W2063407098
- Cited by
- 142
- References
- 61
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 8 · 2023: 15 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 20 · 2018: 21 · 2017: 7 · 2016: 8 · 2015: 11
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- CHDI Foundation (CHDI A3794)
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS036999, NS036999)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- presynaptic NMDA receptors, GluN1, BDNF secretion, corticostriatal synapses, long-term potentiation, theta burst stimulation, synaptic plasticity, cortical axons
- MeSH terms
- Animals, Antibodies, Cerebral Cortex, Corpus Striatum, Luminescent Proteins, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Neurons, Synapses, Time Factors, Valine, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Microscopy, Confocal, Excitatory Amino Acid Antagonists, Brain-Derived Neurotrophic Factor, Receptor, trkB, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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