Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium

Synapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust control function. Most prior studies plasticity at the NMJ have centered presynaptic potentiation (PHP). PHP happens when postsynaptic muscle neurotransmitter receptors are impaired, triggering retrograde signaling causes an increase release. As result, normal levels evoked excitation maintained. counterpart depression (PHD). Overexpression vesicular glutamate transporter (VGlut) amplitude spontaneous events. PHD responds challenge by decreasing quantal content (QC) during neurotransmission—again, resulting excitation. We hypothesized there may exist class molecules affects both PHD. Impairment any such molecule could hurt synapse’s ability respond significant challenge. conducted electrophysiology-based screen for blocks did not observe block genetic conditions screened, but we found loss-of-function led substantial deficit combined with VGlut overexpression. causing this phenotype included double heterozygous condition genes encoding inositol trisphosphate receptor (IP 3 R — itpr ) ryanodine ( RyR ). IP Rs RyRs gate calcium release from intracellular stores. Pharmacological agents targeting recapitulated losses these factors, as lowering other sources. Our data consistent idea process underlying especially sensitive presynapse.