Molecular Mechanisms of Neurotransmitter Release Control Distinct Features of Sensory Coding Reliability

Abstract

To survive, animals must recognize reoccurring stimuli. A key requirement for repeated identification of stimuli is reliable representation by the neural code on each encounter. Synaptic transmission underlies neural codes propagation between brain regions. A hallmark of chemical synapses is their plasticity, which enables signal transfer to be modified in an activity-dependent manner. Despite many decades of intense research on synapses, it remains unclear how the plastic features of synaptic transmission can maintain reliable neural coding. By studying the olfactory system of Drosophila melanogaster, we aimed to obtain a deeper mechanistic understanding of how synaptic function shapes neural coding reliability in the live, behaving animal. We show that the properties of the active zone (AZ), the presynaptic site of neurotransmitter release, are critical for generating a reliable neural code. Reducing neurotransmitter release probability specifically at AZs of olfactory sensory neurons disrupted both neural coding and behavioral reliability. Strikingly, these defects were rescued within a day by target-specific synaptic plasticity, whereby a homeostatic increase in the number of AZs compensated the drop in release probability. These findings demonstrate an important role for synaptic plasticity in maintaining neural coding reliability and are of pathophysiological interest by uncovering an elegant mechanism through which the neural circuitry can counterbalance perturbations.