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-resp onsive adenylyl cyclase, respectively, are deficient in short-term mem ory. Altered synaptic plasticity has been demonstrated at neuromuscula r junctions in these mutants, but little is known about how their cent ral neurons are affected. We examined this problem by using the ''gian t'' neuron culture, which offers a unique opportunity to analyze mutat ional effects on neuronal activity and the underlying ionic currents i n Drosophila. On the basis of instantaneous frequency and first latenc y of spikes evoked by current steps, four categories of firing pattern s (tonic, adaptive, delayed, and interrupted) were identified in wild- type neurons, revealing interesting parallels to those commonly observ ed in vertebrate CNS neurons. The distinct firing patterns were correl ated with expression of different ratios of 4-aminopyridine- and tetra ethylammonium-sensitive K+ currents. Subsets of dnc and rut neurons di splayed abnormal spontaneous spikes and altered firing patterns. Alter ed frequency coding in mutant neurons was demonstrated further by usin g stimulation protocols involving conditioning with previous activity. Abnormal spike activity and reduced K+ current remained in double-mut ant neurons, suggesting that the opposite effects on cAMP metabolism b y dnc and rut do not counterbalance the mutual functional defects. The aberrant spontaneous activity and altered frequency coding in differe nt stimulus paradigms may present problems in the stability and reliab ility of neural circuits for information processing during certain beh avioral tasks, raising the possibility of modulation in neuronal excit ability as a cellular mechanism underlying learning and memory.