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Volume 17, Number 6,
Issue of March 15, 1997
pp. 2187-2199
Copyright ©1997 Society for Neuroscience
Alterations in Frequency Coding and Activity Dependence of
Excitability in Cultured Neurons of Drosophila Memory
Mutants
Received Oct. 28, 1996; revised Dec. 31, 1996; accepted Jan. 6, 1997.
Ming-Li Zhao and
Chun-Fang Wu
Department of Biological Sciences, University of Iowa, Iowa City,
Iowa 52242
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.
Key words:
dnc;
rut;
cAMP;
spike activity;
learning
and memory;
Drosophila giant neurons;
firing patterns;
potassium currents
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