A genetic analysis of synaptic development: Pre- and postsynaptic dCBP control transmitter release at the Drosophila NMJ

Postsynaptic dCBP (Drosophila homolog of the CREB binding protein) is requi red for presynaptic functional development. Viable, hypomorphic dCBP mutati ons have a similar to 50% reduction in presynaptic transmitter release with out altering the Ca2+ cooperativity of release or synaptic ultrastructure ( total bouton number is increased by 25%-30%). Exogenous expression of dCBP in muscle rescues impaired presynaptic release in the dCBP mutant backgroun d, while presynaptic dCBP expression does not. In addition, overexpression experiments indicate that elevated dCBP can also inhibit presynaptic functi onal development in a manner distinct from the effects of dCBP loss of func tion. Pre- or postsynaptic overexpression of dCBP (in wild type) reduces pr esynaptic release. However, we do not observe an increase in bouton number, and presynaptic overexpression impairs short-term facilitation. These data suggest that dCBP participates in a postsynaptic regulatory system that co ntrols functional synaptic development.