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Updated: May 27, 2025

Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability In Vivo
Published on: March 31, 2016
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.
Abstract:
Synapse formation requires the gradual accumulation of cytomatrix proteins and voltage-gated Ca2+ channels (VDCCs) at presynaptic active zones (AZs) to support neurotransmitter release. To correlate AZ maturation with synaptic output, quantal imaging was performed at serially imaged time-stamped Drosophila synapses. Evoked release strength correlated strongly with AZ age and accumulation of late AZ scaffolds, while immature sites lacking VDCC accumulation supported spontaneous release. To examine how neuronal activity regulates AZ maturation and protein accumulation, the effects of disruptions to SV fusion or action potential generation were analyzed. Decreasing neuronal activity reduced AZ seeding and caused hyperaccumulation of presynaptic material at existing AZs. Although enlarged AZs are also observed in rab3 mutants, activity reduction acted through an independent mechanism that required postsynaptic glutamate receptor-dependent signaling. Together, these data indicate AZ maturation state sets distinct presynaptic release modes and output strength, with neuronal activity shaping both AZ number and size across development.
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