Ca²⁺channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity

Abstract

Synaptic heterogeneity is a hallmark of complex nervous systems that enables reliable and responsive communication in neural circuits. In this study, we investigated the contributions of voltage-gated calcium channels (VGCCs) to synaptic heterogeneity at two closely related Drosophila glutamatergic motor neurons, one low- and one high-Pr. We find that VGCC levels are highly predictive of heterogeneous release probability among individual active zones (AZs) of low- or high-Pr inputs, but not between neuronal subtypes. Underlying organizational differences in the AZ cytomatrix, VGCC composition, and a more compact arrangement of VGCCs alter the relationship between VGCC levels and Pr at AZs of low- vs. high-Pr inputs, explaining this apparent paradox. We further find that the CAST/ELKS AZ scaffolding protein Bruchpilot differentially regulates VGCC levels at low- and high-Pr AZs following acute glutamate receptor inhibition, indicating that synapse-specific organization also impacts adaptive plasticity. These findings reveal intersecting levels of molecular and spatial diversity with context-specific effects on heterogeneity in synaptic strength and plasticity.

Muscle-fiber specific genetic manipulation of Drosophila sallimus severely impacts neuromuscular development, morphology, and physiology

“…AZ assembly has been heavily investigated in Drosophila [45,46]. AZ brp levels strongly correlate with SV release probability, and their density varies considerably in responses to presynaptic structural changes [47][48][49]. Recently, much attention has been focused on the role AZ proteins in homeostatic plasticity in compensating for altered SV release [50][51][52]).…”