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Updated: May 27, 2025
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Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability In Vivo
Published on: March 31, 2016
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Active zone maturation state controls synaptic output and release mode and is differentially regulated by neuronal
Yulia Akbergenova1, Jessica Matthias2, J Troy Littleton1
1The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Biorxiv : the Preprint Server for Biology
|February 20, 2025
Summary
Synapse maturation involves protein buildup at active zones (AZs), influencing neurotransmitter release. Neuronal activity shapes AZ development, affecting both spontaneous and evoked release modes.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Synapse formation requires presynaptic active zone (AZ) maturation, involving cytomatrix protein and voltage-gated Ca2+ channel (VDCC) accumulation.
- Understanding the correlation between AZ maturation and synaptic output is crucial for deciphering neurotransmission regulation.
Purpose of the Study:
- To investigate the relationship between active zone (AZ) maturation and synaptic release strength.
- To explore how neuronal activity influences AZ development, protein accumulation, and presynaptic release modes.
Main Methods:
- Utilized time-stamped, serial imaging of Drosophila synapses to perform quantal imaging.
- Analyzed the impact of disruptions in synaptic vesicle (SV) fusion and action potential generation on AZ maturation.
- Investigated the role of postsynaptic glutamate receptor signaling in activity-dependent AZ regulation.
Main Results:
- Evoked release strength strongly correlated with AZ age and late scaffold accumulation.
- Immature AZs, lacking VDCCs, supported spontaneous neurotransmitter release.
- Reduced neuronal activity decreased AZ seeding and led to hyperaccumulation of presynaptic material, acting independently of Rab3.
- Activity reduction required postsynaptic glutamate receptor signaling for its effects on AZs.
Conclusions:
- Active zone (AZ) maturation state dictates distinct presynaptic release modes and output strength.
- Neuronal activity plays a critical role in regulating both the number and size of AZs during synaptic development.
- Postsynaptic signaling influences activity-dependent presynaptic development.
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