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Related Concept Videos

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Calretinin-Expressing Synapses Show Improved Synaptic Efficacy with Reduced Asynchronous Release during High-Rate

Chuangeng Zhang1, Meijian Wang1, Shengyin Lin1

  • 1Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Columbus, Ohio 43210.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|February 15, 2022
PubMed
Summary

Calretinin (CR) enhances auditory synapse function during high-rate activity by improving synaptic efficacy and reducing depression. CR-expressing synapses show faster recovery and distinct vesicular glutamate transporter expression compared to non-CR synapses.

Keywords:
asynchronous releasecalcium bindingcalretininendbulb of Heldsynaptic efficacysynaptic transmission

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Area of Science:

  • Neuroscience
  • Synaptic Physiology
  • Calcium Signaling

Background:

  • Calretinin (CR) is a calcium-binding protein widely distributed in the central nervous system (CNS).
  • The precise synaptic function of endogenous CR, particularly its role in modulating neurotransmitter release, remains largely undetermined.
  • Selective expression of CR in different subtypes of auditory nerve terminals (endbulb of Held) presents a unique model to study its synaptic impact.

Purpose of the Study:

  • To investigate the role of endogenous calretinin (CR) in synaptic transmission at the endbulb of Held synapses.
  • To compare synaptic properties between CR-expressing and non-CR-expressing auditory nerve terminals.
  • To elucidate how CR influences synaptic efficacy, vesicle release dynamics, and calcium handling during high-frequency stimulation.

Main Methods:

  • Electrophysiology was combined with immunohistochemistry to analyze synaptic transmission.
  • Experiments were conducted on mature CBA/CAJ mice of both sexes.
  • Synaptic function was assessed under basal conditions and during high-rate stimulus trains, with and without EGTA-AM treatment.

Main Results:

  • CR-expressing synapses exhibited larger quantal size and improved synaptic efficacy during high-rate activity, showing less depression and reduced asynchronous release.
  • CR-expressing synapses displayed a smaller readily releasable pool but compensated with higher release probability and faster synaptic recovery.
  • EGTA-AM treatment differentially affected synapses, reducing depression and asynchronous release in non-CR synapses, suggesting CR mitigates calcium accumulation.
  • CR-expressing synapses exclusively utilized the fast VGluT1, while non-CR synapses used both VGluT1 and the slower VGluT2, potentially explaining differences in recovery kinetics.

Conclusions:

  • Differential expression of CR significantly impacts synaptic efficacy and neurotransmitter release dynamics at auditory nerve terminals.
  • CR appears to enhance synaptic performance during high-rate activity by optimizing exocytosis, calcium handling, and vesicle refilling mechanisms.
  • The distinct expression of vesicular glutamate transporters (VGluT1 vs. VGluT1/2) in CR-expressing and non-CR-expressing synapses contributes to their differential functional properties, particularly recovery kinetics.