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

Elife. 2021 Jun 1;10:e66612. doi: 10.7554/eLife.66612.


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 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.

Keywords: CA3; autoreceptors; hippocampus; ionotropic; mouse; neuroscience; presynaptic calcium; rat.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • CA3 Region, Hippocampal / metabolism
  • Calcium / metabolism
  • Calcium Signaling
  • Female
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mossy Fibers, Hippocampal / metabolism*
  • Mossy Fibers, Hippocampal / ultrastructure
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / metabolism
  • Neuronal Plasticity*
  • Pyramidal Cells / metabolism
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / ultrastructure
  • Synaptic Transmission*
  • Time Factors


  • Bdnf protein, mouse
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Gprin1 protein, mouse
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Calcium