Mutations of the genesrutabaga(rut) anddunce(dnc) affect the synthesis and degradation of cAMP, respectively, and disrupt learning inDrosophila. Combined ultrastructural analysis and focal electrophysiological recording in the larval neuromuscular junction revealed a loss of stability and fine tuning of synaptic structure and function in both mutants. Increased ratios of docked/undocked vesicles and poorly defined synaptic specializations characterizeddncsynapses. In contrast,rutboutons possessed fewer, although larger, synapses with lower proportions of docked vesicles. At reduced Ca2+levels, decreased quantal content coupled with an increase in failure rate was seen inrutboutons and reduced pair-pulse facilitation were found in bothrutanddncmutants. At physiological Ca2+levels, strong enhancement, instead of depression, in evoked release was observed in somedncandrutboutons during 10 Hz tetanus. Furthermore, increased variability of synaptic transmission, including fluctuation and asynchronicity of evoked release, paralleled an increase in synapse size variation in bothdncandrutboutons, which might impose problems for effective signal processing in the nervous system. Pharmacological and genetic studies indicated broader ranges of physiological alteration bydncandrutmutations than either the acute effects of cAMP analogs or the available mutations that affect cAMP-dependent protein kinase (PKA) activity. This is consistent with previous reports of more severe learning defects indncandrutmutations than these PKA mutants and allows identification of the phenotypes involving long-term developmental regulation and those conferred by PKA.

Renger, J. J., Ueda, A., Atwood, H. L., Govind, C. K., & Wu, C.-F. (2000). Role of cAMP Cascade in Synaptic Stability and Plasticity: Ultrastructural and Physiological Analyses of Individual Synaptic Boutons inDrosophilaMemory Mutants. The Journal of Neuroscience, 20(11), 3980–3992.