Differential Regulation of Evoked and Spontaneous Release by Presynaptic NMDA Receptors - PubMed

Affiliations

• PMID: 29033205
• DOI: 10.1016/j.neuron.2017.09.030

Free article

Differential Regulation of Evoked and Spontaneous Release by Presynaptic NMDA Receptors

Therése Abrahamsson et al. Neuron. 2017.

Free article

Abstract

Presynaptic NMDA receptors (preNMDARs) control synaptic release, but it is not well understood how. Rab3-interacting molecules (RIMs) provide scaffolding at presynaptic active zones and are involved in vesicle priming. Moreover, c-Jun N-terminal kinase (JNK) has been implicated in regulation of spontaneous release. We demonstrate that, at connected layer 5 pyramidal cell pairs of developing mouse visual cortex, Mg²⁺-sensitive preNMDAR signaling upregulates replenishment of the readily releasable vesicle pool during high-frequency firing. In conditional RIM1αβ deletion mice, preNMDAR upregulation of vesicle replenishment was abolished, yet preNMDAR control of spontaneous release was unaffected. Conversely, JNK2 blockade prevented Mg²⁺-insensitive preNMDAR signaling from regulating spontaneous release, but preNMDAR control of evoked release remained intact. We thus discovered that preNMDARs signal differentially to control evoked and spontaneous release by independent and non-overlapping mechanisms. Our findings suggest that preNMDARs may sometimes signal metabotropically and support the emerging principle that evoked and spontaneous release are distinct processes. VIDEO ABSTRACT.

Keywords: 2-photon microscopy; computer model; electrophysiology; neocortex; neurotransmitter release; patch clamp; short-term plasticity; uncaging.

Similar articles

• Presynaptic NMDA receptor mechanisms for enhancing spontaneous neurotransmitter release.

  Kunz PA, Roberts AC, Philpot BD. Kunz PA, et al. J Neurosci. 2013 May 1;33(18):7762-9. doi: 10.1523/JNEUROSCI.2482-12.2013. J Neurosci. 2013. PMID: 23637168 Free PMC article.

• Target-specific expression of presynaptic NMDA receptors in neocortical microcircuits.

  Buchanan KA, Blackman AV, Moreau AW, Elgar D, Costa RP, Lalanne T, Tudor Jones AA, Oyrer J, Sjöström PJ. Buchanan KA, et al. Neuron. 2012 Aug 9;75(3):451-66. doi: 10.1016/j.neuron.2012.06.017. Neuron. 2012. PMID: 22884329 Free PMC article.

• Towards resolving the presynaptic NMDA receptor debate.

  Bouvier G, Larsen RS, Rodríguez-Moreno A, Paulsen O, Sjöström PJ. Bouvier G, et al. Curr Opin Neurobiol. 2018 Aug;51:1-7. doi: 10.1016/j.conb.2017.12.020. Epub 2018 Jan 30. Curr Opin Neurobiol. 2018. PMID: 29454833 Review.

• Presynaptic GABAA receptors facilitate spontaneous glutamate release from presynaptic terminals on mechanically dissociated rat CA3 pyramidal neurons.

  Jang IS, Nakamura M, Ito Y, Akaike N. Jang IS, et al. Neuroscience. 2006;138(1):25-35. doi: 10.1016/j.neuroscience.2005.11.001. Epub 2005 Dec 27. Neuroscience. 2006. PMID: 16378694

• Roles of Presynaptic NMDA Receptors in Neurotransmission and Plasticity.

  Banerjee A, Larsen RS, Philpot BD, Paulsen O. Banerjee A, et al. Trends Neurosci. 2016 Jan;39(1):26-39. doi: 10.1016/j.tins.2015.11.001. Epub 2015 Dec 23. Trends Neurosci. 2016. PMID: 26726120 Free PMC article. Review.

Cited by

• Prenatal Exposure to Ethanol Alters Synaptic Activity in Layer V/VI Pyramidal Neurons of the Somatosensory Cortex.

  Delatour LC, Yeh PWL, Yeh HH. Delatour LC, et al. Cereb Cortex. 2020 Mar 14;30(3):1735-1751. doi: 10.1093/cercor/bhz199. Cereb Cortex. 2020. PMID: 31647550 Free PMC article.

• Plasticity in the functional properties of NMDA receptors improves network stability during severe energy stress.

  Bueschke N, Amaral-Silva L, Hu M, Alvarez A, Santin JM. Bueschke N, et al. bioRxiv [Preprint]. 2023 Oct 16:2023.01.19.524811. doi: 10.1101/2023.01.19.524811. bioRxiv. 2023. PMID: 36711958 Free PMC article. Updated. Preprint.

• Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses.

  Lituma PJ, Kwon HB, Alviña K, Luján R, Castillo PE. Lituma PJ, et al. Elife. 2021 Jun 1;10:e66612. doi: 10.7554/eLife.66612. Elife. 2021. PMID: 34061025 Free PMC article.

• Ion flux-independent NMDA receptor signaling.

  Park DK, Stein IS, Zito K. Park DK, et al. Neuropharmacology. 2022 Jun 1;210:109019. doi: 10.1016/j.neuropharm.2022.109019. Epub 2022 Mar 9. Neuropharmacology. 2022. PMID: 35278420 Free PMC article. Review.

• Active Zone Proteins RIM1αβ Are Required for Normal Corticostriatal Transmission and Action Control.

  Kupferschmidt DA, Augustin SM, Johnson KA, Lovinger DM. Kupferschmidt DA, et al. J Neurosci. 2019 Feb 20;39(8):1457-1470. doi: 10.1523/JNEUROSCI.1940-18.2018. Epub 2018 Dec 17. J Neurosci. 2019. PMID: 30559150 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • scite Smart Citations

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal
  • SciCrunch