Distinct functions of neuronal synaptobrevin in developing and mature fly photoreceptors

Neuronal synaptobrevin (n-Syb, alias VAMP2), a synaptic vesicle membrane protein with a central role in neurotransmission, is specifically cleaved by the light chain of tetanus neurotoxin (TNT) that is known to reliably block neuroexocytosis. Here, we study fly photoreceptors transmitting continuous, graded signals to first order interneurons in the lamina, and report consequences of targeted expression of TNT in these cells using the UAS/GAL4 driver/effector system. Expressing the toxin throughout photoreceptor development causes developmental, electrophysiological, and behavioral defects. These can be differentiated by confining toxin expression to shorter developmental periods. Applying a method for controlled temporal and spatial TNT expression, we found that in the early pupa it impaired the development of the retina; in the midpupa, during synapse formation TNT caused a severe hypoplasia of the lamina that persisted into adulthood and left the photoreceptor-interneuron synapses of the lamina without function. Finally, during adulthood TNT neither blocks synaptic transmission in photoreceptors nor depletes the cells of n-Syb. Our study suggests a novel, cell type-specific function of n-Syb in synaptogenesis and it distinguishes between two synapse types: TNT resistant and TNT sensitive ones. These results need to be taken into account if TNT is used for neural circuit analysis.