Molecular Enhancement of Memory Formation

pulses of serotonin (5-hydroxytryptamine; 5-HT), a Department of Psychology transmitter released by tail stimuli (Montarolo et al., Department of Biology 1986; Emptage and Carew, 1993); this facilitation criti-Yale University cally depends on protein synthesis (Montarolo et al., New Haven, Connecticut 06520 1986). Repeated 5-HT pulses also cause an increase in cAMP in the sensory neurons and give rise to transloca-tion of the catalytic subunit of the cAMP-dependent protein kinase (PKA) to the sensory neuron nucleus A mathematician friend of mine tells the story of a col-(Bacskai et al., 1993), where it appears to activate cAMP-league at her university, an ichthyologist, who pro-inducible gene expression (Kaang et al., 1993). Finally, claimed that he actively avoided remembering the repeated 5-HT pulses and cAMP also induce protein names of the students he taught. When she admonished synthesis–dependent, long-lasting structural changes in him for this point of view, he explained it simply: " Re-sensory neurons (reviewed in Bailey and Kandel, 1993). member a name, forget a fish. " This is admittedly a In Drosophila, cAMP has been implicated in an impor-rather simplified view of memory, but it highlights the tant role in long-term memory produced in a form of important point that committing an event to long-term olfactory avoidance learning in which flies are presented memory is serious business. Typically, the encoding of with two novel odors, one of which is paired with an a lasting memory entails considerable practice and rehearsal , but we are all also aware of those rare events electric shock. After training, flies express memory for in our lives that are so powerful as to be instantly en-the task by avoiding the odor that was paired with shock coded and remembered for a lifetime. Quite remarkably, (Tully and Quinn, 1985). With repeated, temporally insights into these fundamental properties of memory spaced training trials, an enduring memory that requires are beginning to emerge from an analysis of their under-protein synthesis is formed (Tully et al., 1994). Using a lying molecular substrates. forward genetic approach, several fly mutants that ex-A critical step in our understanding of the neuronal hibit memory deficits for this type of learning have been mechanisms of memory was the appreciation that the shown to be impaired in the cAMP signaling cascade. formation of long-lasting memories requires protein syn-These include animals with a disrupted phosphodiester-thesis (reviewed in Davis and Squire, 1984). Recent work ase gene (dunce), a defective …