Prolonged habituation of the gill-withdrawal reflex in Aplysia depends on protein synthesis, protein phosphatase activity, and postsynaptic glutamate receptors - PubMed (original) (raw)
Prolonged habituation of the gill-withdrawal reflex in Aplysia depends on protein synthesis, protein phosphatase activity, and postsynaptic glutamate receptors
Youssef Ezzeddine et al. J Neurosci. 2003.
Abstract
Despite representing perhaps the simplest form of memory, habituation is not yet well understood mechanistically. We used a reduced preparation to analyze the neurobiological mechanisms of persistent habituation of a simple behavior, the defensive withdrawal reflex of the marine snail Aplysia californica. This preparation permits direct infusion of drugs into the abdominal ganglion during training via a cannula in the abdominal artery. Using siphon-elicited gill withdrawal, we demonstrate habituation of withdrawal that persists for 1-6 hr after repeated, spaced blocks of habituating stimulation. This form of habituation exhibits site specificity and requires protein synthesis because it is blocked by the presence of anisomycin, a protein synthesis inhibitor. We also find that habituation of gill withdrawal requires protein phosphatase activity, because it is blocked by okadaic acid, an inhibitor of protein phosphatase. Finally, habituation of gill withdrawal requires activation of NMDA-type and AMPA-type postsynaptic receptors within the abdominal ganglion, because it is blocked by infusion of dl-2-amino-5-phosphonovaleric acid or 6,7-dinitroquinoxaline-2,3-dione. The requirement for activation of postsynaptic glutamatergic receptors indicates that homosynaptic depression, an exclusively presynaptic mechanism that has been implicated previously in habituation in Aplysia, does not play a significant role in persistent habituation of the withdrawal reflex. Our results indicate that postsynaptic mechanisms, possibly including modulation of glutamate receptor function, play a major, heretofore unsuspected, role in habituation in Aplysia.
Figures
Figure 1.
Reduced preparation of Aplysia used for experiments investigating habituation of siphon-elicited gill withdrawal. The abdominal ganglion is shown artificially enlarged relative to the other central ganglia. The preparation shown is that used for the within-preparation experiments. The preparation used for the between-preparation experiments (Fig. 2) was similar, but only one site on the siphon was stimulated.
Figure 2.
Long-lasting habituation of gill withdrawal in a reduced preparation. Gill withdrawal in reduced preparations that received spaced blocks of habituation training. Only one site on the siphon was stimulated in these experiments.
Figure 3.
Effect of anisomycin on long-lasting habituation. A, Results from training in normal ASW. Averaged gill responses to trained-site stimulation in this and subsequent graphs are represented by filled circles; averaged responses to untrained-site stimulation are represented by open squares. Traces shown above the graph represent individual gill-withdrawal responses from a single experiment recorded using a force transducer (see Materials and Methods). From left to right, The response to the first trained-site pretest and the response to the untrained-site pretest are shown superimposed. (In this and subsequent figures, responses to trained-site stimulation are in black, and responses to untrained-site stimulation are in gray.) Next, five superimposed gill responses (those to stimuli 1, 3, 8, 13, and 20) from each of the four training blocks are presented sequentially. (These responses, except for the first and last responses of each block, were selected at random.) Finally, the response to the first trained-site posttest and the response to the untrained-site posttest are shown superimposed. B, Results from habituation training in the presence of the protein synthesis inhibitor anisomycin. Traces at top are the individual gill responses recorded during a single experiment. For details, see legend in A. Notice that the reflex exhibited significant interblock sensitization during training, as indicated by the increase in withdrawal responses to the first several stimuli of each training block.
Figure 4.
Effect of okadaic acid on long-lasting habituation. A, Results from training in the presence of okadaic acid. The drug was present throughout the experiments. Notice that the reflex exhibited interblock sensitization during training, as indicated by the increase in withdrawal responses to the first several stimuli of each training block. B, Results from habituation training in the presence of 1-nor-okadone. The drug was present throughout the experiments. Traces shown above the graphs in A and B are the individual gill responses recorded during a single experiment. For details, see the legend in Figure 3_A_.
Figure 5.
Effect of APV on long-lasting habituation. A, Results from training in the presence of APV. The drug was present throughout the experiments. (For results from experiments in which APV was present only during training, see Results.) Notice that the reflex exhibited significant interblock sensitization during training, as indicated by the increase in withdrawal responses to the first several stimuli of each training block. B, Results from habituation training in normal ASW without APV. Traces shown above the graphs in A and B are the individual gill responses recorded during a single experiment. For details, see the legend in Figure 3_A_.
Figure 6.
Effect of DNQX on long-lasting habituation. A, Results from training in the presence of DNQX. The drug was present only during the training, as indicated by the black line. Notice that the responses evoked during training in the presence of DNQX were greatly reduced but not completely eliminated (for discussion, see Results). B, Results from habituation training in ASW with 0.2% DMSO. Traces shown above the graphs in A and B are the individual gill responses recorded during a single experiment. The set of traces shown with each graph are from one preparation. For details, see the legend in Figure 3_A_.
References
- Antonov I, Antonova I, Kandel ER, Hawkins RD ( 2003) Activity-dependent presynaptic facilitation and Hebbian LTP are both required and interact during classical conditioning in Aplysia. Neuron 37: 135-147. - PubMed
- Bailey CH, Chen M ( 1983) Morphological basis of long-term habituation and sensitization in Aplysia. Science 220: 91-93. - PubMed
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