Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses
- Albert Einstein College of Medicine, United States
- Johns Hopkins University, United States
- Universidad de Castilla-La Mancha, Spain
Abstract
Neurotransmitter release is a highly controlled process by which synapses can critically regulate information transfer within neural circuits. While presynaptic receptors –typically activated by neurotransmitters and modulated by neuromodulators– provide a powerful way of fine-tuning synaptic function, their contribution to activity-dependent changes in transmitter release remains poorly understood. Here, we report that presynaptic NMDA receptors (preNMDARs) at mossy fiber boutons in the rodent hippocampus can be activated by physiologically relevant patterns of activity and selectively enhance short-term synaptic plasticity at mossy fiber inputs onto CA3 pyramidal cells and mossy cells, but not onto inhibitory interneurons. Moreover, preNMDARs facilitate brain-derived neurotrophic factor (BDNF) release and contribute to presynaptic calcium rise. Taken together, our results indicate that by increasing presynaptic calcium, preNMDARs fine tune mossy fiber neurotransmission and can control information transfer during dentate granule cell burst activity that normally occur in vivo.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Institutes of Health (R01 MH116673)
- Pablo E Castillo
National Institutes of Health (R01 MH125772)
- Pablo E Castillo
National Institutes of Health (R01 NS113600)
- Pablo E Castillo
National Institutes of Health (F31 MH 109267)
- Pablo J Lituma
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal handling followed an approved protocol by the Albert Einstein College of Medicine Institutional Animal Care and Use Committee (IACUC protocols 00001043, 00001047 and 00001053) in accordance with National Institute of Health guidelines.
Copyright
© 2021, Lituma et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses
eLife 10:e66612.
https://doi.org/10.7554/eLife.66612
