Activity-Dependent Postsynaptic Mitochondrial ROS Signaling Drives Avoidance Plasticity in C. elegans

Area of Science:

• Neuroscience
• Cellular Biology
• Genetics

Background:

• Reactive oxygen species (ROS) are key signaling molecules in neuronal function.
• Mitochondrial ROS (mitoROS) are involved in metabolic regulation and stress responses.
• The role of acute mitoROS elevations in synaptic plasticity is not well understood.

Purpose of the Study:

• To investigate the influence of mitoROS on synaptic plasticity and behavior.
• To establish an optogenetic paradigm for studying avoidance sensitization in C. elegans.
• To elucidate the mechanisms by which mitoROS signaling modulates neuronal circuits.

Main Methods:

• Developed an optogenetic avoidance sensitization paradigm in C. elegans.
• Utilized ASH neuron activation to induce avoidance reversals via AVA interneurons.
• Measured synaptic plasticity through surface glutamate receptor (GLR-1) levels.
• Assessed mitoROS production and its dependence on GLR-1 and MCU-1.
• Employed postsynaptic photoactivation of mitochondria-targeted Killer Red to test sufficiency.

Main Results:

• Optogenetic training induced behavioral sensitization (increased reversal probability) 4 hours post-training.
• Avoidance sensitization correlated with increased surface GLR-1 at ASH-AVA synapses.
• Mitochondria in AVA neurons produced ROS post-training, dependent on GLR-1 and MCU-1.
• Postsynaptic mitoROS signaling was sufficient to induce avoidance sensitization, bypassing training and MCU-1.

Conclusions:

• Activity-dependent mitoROS signaling instructs synaptic strengthening.
• MitoROS directly modulates neuronal circuit function and behavior.
• This study reveals a novel signaling pathway where mitoROS regulates synaptic plasticity and learning.