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Published on: August 7, 2019
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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.
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.
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.
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