Postsynaptic Stability and Variability Described by a Stochastic Model of Endosomal Trafficking

Area of Science:

• Neuroscience
• Cell Biology
• Systems Biology

Background:

• Neurons maintain synaptic efficacy through constitutive AMPA-type glutamate receptor (AMPAR) trafficking, involving exocytosis and endocytosis.
• Synaptic plasticity mechanisms and AMPAR trafficking exhibit fluctuating and stochastic properties, posing a challenge to understanding stability.
• Existing deterministic models do not account for stochasticity in endosomal trafficking, limiting their explanatory power.

Purpose of the Study:

• To investigate how the endosomal trafficking system reconciles stability and stochasticity in regulating postsynaptic AMPARs.
• To determine if stability is achieved despite fluctuating trafficking processes and how variability influences long-term synaptic depression (LTD).

Main Methods:

• Developed a novel stochastic model incorporating fluctuations into key endosomal trafficking machinery.
• Applied the model to analyze AMPAR regulation at the basal state and during LTD.
• Investigated the relationship between stochasticity, variability in LTD, and late endosome (LE) sorting timing.

Main Results:

• The stochastic model demonstrated stable regulation of postsynaptic AMPAR numbers under basal conditions and during LTD.
• High variability in AMPAR numbers and LTD time course and magnitude were observed, consistent with experimental data.
• Stochasticity was found to be beneficial for maintaining consistent timing of LE sorting during LTD.

Conclusions:

• The coexistence of stability and stochasticity in the endosomal trafficking system supports stable synaptic transmission.
• This dual property enables reliable induction of synaptic plasticity with experimentally observed variable characteristics.
• The stochastic model provides a framework for understanding the complex regulation of AMPARs in neuronal function and plasticity.