Mutants of the Drosophila dunce and rutabaga 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. This problem was examined 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 are correlated with expression of different ratios of 4-aminopyridine- and tetra ethylammonium-sensitive K+ currents. Subsets of dnc and rut neurons display 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 remain 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, 1997). Not all memory genes first identified in other contexts, however, play a significant role in place memory. The DopEcR gene has been implicated in several behaviors, including a 30 min memory after courtship conditioning. This G-protein linked receptor is responsive to both dopamine and the steroid hormone ecdysone. Remarkably, DopEcR has been shown to interact with the cAMP cascade through double mutant and pharmacological tests. Using conditions that induce a robust and lasting place memory, the DopEcR mutant flies do not show a defect in memory directly after training or at 1 h post-training. This is despite the fact that the rut and cAMP-phosphodiesterase genes (dunce) are critical for place memory. It may be that DopEcR is not required for this type of learning and would be consistent with the independence of place memory from dopamine signaling. Alternatively, other redundant pathways may compensate for the reduction in DopEcR function caused by the DopEcRPB1 allele. One might further speculate that other types of behavioral plasticity, such as reversal learning or memory enhancement after unpredicted high temperature exposures in the heat-box might be more sen.

1. Mutants of the Drosophila dunce and rutabaga 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. This problem was examined 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 are correlated with expression of different ratios of 4-aminopyridine-
and tetra ethylammonium-sensitive K+ currents. Subsets of dnc and rut neurons display
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 remain 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, 1997).
Not all memory genes first identified in other contexts, however, play a significant role in place
memory. The DopEcR gene has been implicated in several behaviors, including a 30 min
memory after courtship conditioning. This G-protein linked receptor is responsive to both
dopamine and the steroid hormone ecdysone. Remarkably, DopEcR has been shown to interact
with the cAMP cascade through double mutant and pharmacological tests. Using conditions that
induce a robust and lasting place memory, the DopEcR mutant flies do not show a defect in
memory directly after training or at 1 h post-training. This is despite the fact that the rut and
cAMP-phosphodiesterase genes (dunce) are critical for place memory. It may be that DopEcR is
not required for this type of learning and would be consistent with the independence of place
memory from dopamine signaling. Alternatively, other redundant pathways may compensate for
the reduction in DopEcR function caused by the DopEcRPB1 allele. One might further speculate
that other types of behavioral plasticity, such as reversal learning or memory enhancement after
unpredicted high temperature exposures in the heat-box might be more sensitive to DopEcR
changes. Future experiments will determine if this is the case (Ostrowski, 2014).

2. Memory stability across learning contexts in Drosophila has some common genetic mechanisms,
but the timing for gene action depends on the type of learning. That this study has added several
genes here, including lat, pst, and rac as regulators of memory stability in operant place memory
suggests that there are at least some common molecular processes in memory stability across
different learning types. However, the timing of these genetically-defined phases depends on
what is learnt. It is speculated that an ideal system to regulate memory stability would be one that
activates its own decline. That is, a given memory type should activate the process of decreasing
memory expression. This might work with the recruitment of a reinforcing pathway, like the
dopaminergic signal that is important for both the acquisition of an associative olfactory memory
and the active process of forgetting that association. In this case an odor associated with shock
gives rise to a memory trace in mushroom body neurons that depends on a set of dopamine
neurons that is important for both memory acquisition and decline. Whether this type of
aminergic-based system applies to other forms of memory is not yet known. However, if an
aminergic-based signal is common in memory decline, as appears to be the case with the Rac-
based mechanism, differences in the types of aminergic neurons or innervation targets could give
rise to the altered stabilities of behaviorally expressed memories (Ostrowski, 2014).
Solution
Mutants of the Drosophila dunce and rutabaga 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. This problem was examined 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 are correlated with expression of different ratios of 4-aminopyridine-
and tetra ethylammonium-sensitive K+ currents. Subsets of dnc and rut neurons display
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 remain 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

3. 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, 1997).
Not all memory genes first identified in other contexts, however, play a significant role in place
memory. The DopEcR gene has been implicated in several behaviors, including a 30 min
memory after courtship conditioning. This G-protein linked receptor is responsive to both
dopamine and the steroid hormone ecdysone. Remarkably, DopEcR has been shown to interact
with the cAMP cascade through double mutant and pharmacological tests. Using conditions that
induce a robust and lasting place memory, the DopEcR mutant flies do not show a defect in
memory directly after training or at 1 h post-training. This is despite the fact that the rut and
cAMP-phosphodiesterase genes (dunce) are critical for place memory. It may be that DopEcR is
not required for this type of learning and would be consistent with the independence of place
memory from dopamine signaling. Alternatively, other redundant pathways may compensate for
the reduction in DopEcR function caused by the DopEcRPB1 allele. One might further speculate
that other types of behavioral plasticity, such as reversal learning or memory enhancement after
unpredicted high temperature exposures in the heat-box might be more sensitive to DopEcR
changes. Future experiments will determine if this is the case (Ostrowski, 2014).
Memory stability across learning contexts in Drosophila has some common genetic mechanisms,
but the timing for gene action depends on the type of learning. That this study has added several
genes here, including lat, pst, and rac as regulators of memory stability in operant place memory
suggests that there are at least some common molecular processes in memory stability across
different learning types. However, the timing of these genetically-defined phases depends on
what is learnt. It is speculated that an ideal system to regulate memory stability would be one that
activates its own decline. That is, a given memory type should activate the process of decreasing
memory expression. This might work with the recruitment of a reinforcing pathway, like the
dopaminergic signal that is important for both the acquisition of an associative olfactory memory
and the active process of forgetting that association. In this case an odor associated with shock
gives rise to a memory trace in mushroom body neurons that depends on a set of dopamine
neurons that is important for both memory acquisition and decline. Whether this type of
aminergic-based system applies to other forms of memory is not yet known. However, if an
aminergic-based signal is common in memory decline, as appears to be the case with the Rac-
based mechanism, differences in the types of aminergic neurons or innervation targets could give
rise to the altered stabilities of behaviorally expressed memories (Ostrowski, 2014).