Behavioral, Cellular, and Molecular Analysis of Memory in Aplysia I: Intermediate-Term Memory

M A Sutton

doi:10.1093/icb/42.4.725

Abstract

Serotonin (5HT) induces short-term and long-term synaptic facilitation (STF and LTF, respectively) at sensory neuron to motor neuron (SN-MN) synapses in Aplysia, and these forms of plasticity are thought to contribute to short-term and long-term memory for behavioral sensitization. Recent evidence in Aplysia has identified a third phase of synaptic facilitation-intermediate-term facilitation (ITF)-that is temporally and mechanistically distinct from STF and LTF. Here, we review the findings of recent studies that have examined this unique intermediate-term phase at molecular, cellular, and behavioral levels. The results indicate that, at tail SN-MN synapses, multiple forms of ITF can be distinguished; they are induced via distinct mechanisms and use parallel molecular pathways for their expression. Moreover, we have incorporated the temporal and molecular features of these different forms of ITF at tail SN-MN synapses into behavioral analyses, and found that they accurately predict distinct forms of intermediate-term memory for sensitization of the tail-elicited siphon withdrawal reflex. These findings indicate that different types of experiences engage distinct molecular pathways in the service of memory retention over the same time domain.

Highlights

Since the transient activation of protein kinase (PKA) can induce STF, this raised the hypothesis that the intermediate-term persistent activation of PKA observed after 5 pulses of 5HT might be a mechanism contributing to the expression of intermediate-term facilitation (ITF) induced in the same fashion. We found that this was the case: the PKA inhibitor KT 5720, which blocks the catalytic activity of PKA downstream of potential activators, completely blocked ITF that had previously been established by 5 pulses of 5HT (Sutton and Carew, 2000)
One can ask whether the temporal and mechanistic features of ITF predict one or more forms of intermediate-term memory (ITM) for sensitization. We initially explored this issue by taking advantage of the fact that, in the absence of intrinsic sensory neurons (SNs) activity, ITF at tail sensory neuron to motor neuron (SN-motor neurons (MNs)) synapses has a number of distinguishing characteristics: 1) it requires repeated pulses of 5HT (e.g., 5), whereas STF can be induced with a single pulse; 2) it persists far longer than STF (Ͻ30 min), yet completely decays several hours prior to the emergence of LTF (10–15 hr; Mauelshagen et al, 1996); 3) it requires translation of new protein but not transcription of mRNA; and 4) its expression can be reversibly blocked by transient inhibition of the catalytic activity of PKA
The analysis of ITM in Aplysia has yielded several insights into the underlying cellular and molecular mechanisms that contribute to memory processing

Summary

Behavioral, Cellular, and Molecular Analysis of Memory in Aplysia I: Intermediate-Term Memory. These results have served to establish 5HT-induced facilitation of SN-MN synapses as a useful cellular model of both short-term and long-term memory for behavioral sensitization. The induction of ITF required translation but not transcription, which distinguished this phase from STF and LTF at the mechanistic level, since STF requires neither protein nor RNA synthesis, and LTF requires both (Montarolo et al, 1986; Ghirardi et al, 1995) Together, these results provided definitive evidence for a novel intermediate phase of synaptic facilitation expressed by SN-MN synapses in cell culture. These results demonstrated an intriguing feature regarding the organization of different phases of synaptic facilitation at tail SN-MN synapses: the intermediate-term and long-term phases of facilitation are temporally discontinuous

SIGNALING PATHWAYS ENGAGED DURING ITF

ITM HAS A UNIQUE MOLECULAR SIGNATURE

THE FEATURES OF ITM EXPRESSION REVEAL UNIQUE PROCESSES RESPONSIBLE FOR INDUCTION

SUMMARY AND CONCLUSIONS