Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

PLoS Biol. 2021 Jun 21;19(6):e3001149. doi: 10.1371/journal.pbio.3001149. eCollection 2021 Jun.

Abstract

Synaptic plasticity is a cellular model for learning and memory. However, the expression mechanisms underlying presynaptic forms of plasticity are not well understood. Here, we investigate functional and structural correlates of presynaptic potentiation at large hippocampal mossy fiber boutons induced by the adenylyl cyclase activator forskolin. We performed 2-photon imaging of the genetically encoded glutamate sensor iGluu that revealed an increase in the surface area used for glutamate release at potentiated terminals. Time-gated stimulated emission depletion microscopy revealed no change in the coupling distance between P/Q-type calcium channels and release sites mapped by Munc13-1 cluster position. Finally, by high-pressure freezing and transmission electron microscopy analysis, we found a fast remodeling of synaptic ultrastructure at potentiated boutons: Synaptic vesicles dispersed in the terminal and accumulated at the active zones, while active zone density and synaptic complexity increased. We suggest that these rapid and early structural rearrangements might enable long-term increase in synaptic strength.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colforsin / pharmacology
  • Glutamic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence, Multiphoton
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / metabolism*
  • Mossy Fibers, Hippocampal / ultrastructure
  • Neurotransmitter Agents / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism

Substances

  • Neurotransmitter Agents
  • Colforsin
  • Glutamic Acid

Grants and funding

This study is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC-2049 – 390688087 to D.S. and S.J.S., DFG project 327654276 – SFB 1315 to D.S. and S.J.S., DFG project 184695641 – SFB 958 to D.S. and S.J.S., DFG project 431572356 to D.S., DFG project 273915538 – SPP 1926 to B.R.R. and DFG project 365082554 - FOR 2705 to S.J.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.