Synapses are the fundamental building blocks of the nervous system. Following target cell contact, they are formed through a process that requires the precise orchestration of both pre- and postsynaptic differentiation of synaptic machinery. However, the precise time course of synaptogenesis, and the role of extrinsic factors in synapse formation remains unclear. To examine the time course of synaptogenesis, I developed a novel “growth ball” model to study synapse at the level of isolated growth cones. Specifically, I found that functional synapses can reform in isolated growth cones within minutes of contact with their synaptic partner. However, in the absence of the cell body, these synapses cannot be maintained.
To further investigate the importance of the cell body, I demonstrate that extrinsic trophic factors can “prime” postsynaptic neurons for synapse formation through the functional expression of excitatory acetylcholine receptors via activity dependent mechanisms. Specifically, trophic factor induced activity follows a specific pattern of progression, which I termed an activity “signature”, that is necessary for proper expression of excitatory acetylcholine receptors.
Finally, I demonstrate and characterize a novel form of use-dependent short-term potentiation that is observed in the visceral dorsal 1/left pedal dorsal 1 synapse. This synaptic plasticity is induced rapidly by a short presynaptic tetanic pulse and remains potentiated until a subsequent action potential is triggered in a use- rather than time-dependent manner. I show that the molecular switch underlying this form of potentiation is calcium/calmodulin kinase II (CaMKII). Taken together, these studies demonstrate both intrinsic and extrinsic mechanisms of synapse formation and identify a novel role for CaMKII in a use-dependent form of synaptic plasticity.