In vivo synaptic recovery following optogenetic hyperstimulation
Maike Kittelmann1, Jana F Liewald, Jan Hegermann
1European Neuroscience Institute and Center for Molecular Physiology of the Brain, Georg August University, D-37077 Göttingen, Germany.
Summary
Neurons recover synaptic function slowly after intense activity. New bulk endocytosis mechanisms involving intermediate vesicles regenerate synaptic vesicles (SVs) in animals, similar to processes potentially aiding seizure recovery.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Local recycling of synaptic vesicles (SVs) is crucial for sustained neurotransmitter release.
- Extreme neuronal activity can exhaust synaptic transmission, triggering bulk endocytosis in vitro for SV membrane and protein recovery.
- The in vivo mechanisms of bulk endocytosis and subsequent synaptic recovery in animals remain largely unknown.
Purpose of the Study:
- To investigate the in vivo mechanisms of synaptic recovery following exhaustive neuronal activity in Caenorhabditis elegans.
- To characterize the dynamics of synaptic vesicle regeneration and functional recovery at different biological levels.
- To identify key molecular players involved in bulk endocytosis and SV regeneration.
Main Methods:
- Optogenetic hyperstimulation of Caenorhabditis elegans motoneurons.
- Time-resolved behavioral, electrophysiological, and ultrastructural assays to analyze synaptic recovery.
- Analysis of endocytosis and vesicle scission mutants (endophilin, synaptojanin, dynamin) to assess their role in recovery.
Main Results:
- Recovery of docked SVs and evoked-release amplitudes occurred within approximately 8-20 seconds.
- Locomotion recovery was significantly slower, taking around 60 seconds.
- Noncoated intermediate vesicles (50-200 nm) formed during stimulation and resolved post-stimulation, with their dynamics altered in endocytosis mutants, implicating dynamin in SV regeneration from bulk-endocytosed vesicles.
Conclusions:
- Synaptic recovery after exhaustive activity is a slow process involving multiple contributing mechanisms operating at different time scales.
- Intermediate vesicles observed during bulk endocytosis are likely key players in regenerating synaptic vesicles.
- These findings suggest that similar mechanisms may underlie the slow recovery from acute seizures in higher animals.
