Alterations in frequency coding and activity dependence of excitability in cultured neurons of Drosophila memory mutants.
Mutants of the Drosophila dunce (dnc) and rutabaga (rut) genes, which encode a cAMP-specific phosphodiesterase and a calcium/calmodulin-responsive adenylyl cyclase, respectively, are deficient in short-term memory. Altered synaptic plasticity has been demonstrated at neuromuscular junctions in these mutants, but little is known about how their central neurons are affected. We examined this problem by using the "giant" neuron culture, which offers a unique opportunity to analyze mutational effects on neuronal activity and the underlying ionic currents in Drosophila. On the basis of instantaneous frequency and first latency of spikes evoked by current steps, four categories of firing patterns (tonic, adaptive, delayed, and interrupted) were identified in wild-type neurons, revealing interesting parallels to those commonly observed in vertebrate CNS neurons. The distinct firing patterns were correlated with expression of different ratios of 4-aminopyridine- and tetraethylammonium-sensitive K+ currents. Subsets of dnc and rut neurons displayed abnormal spontaneous spikes and altered firing patterns. Altered frequency coding in mutant neurons was demonstrated further by using stimulation protocols involving conditioning with previous activity. Abnormal spike activity and reduced K+ current remained in double-mutant neurons, suggesting that the opposite effects on cAMP metabolism by dnc and rut do not counterbalance the mutual functional defects. The aberrant spontaneous activity and altered frequency coding in different stimulus paradigms may present problems in the stability and reliability of neural circuits for information processing during certain behavioral tasks, raising the possibility of modulation in neuronal excitability as a cellular mechanism underlying learning and memory.
Zhao
M L
ML
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA.
Wu
C F
CF
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila; D005260:Female; D008568:Memory / Q000502:physiology*; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques