(2) cAMP

cAMP binding to an enzyme

Of all the known second-messengers, the cAMP system is probably the most primitive. It is the most important, and in some cases the only second-messenger system found in single-celled organisms such as the bacterium E.CColi, in which it signals hunger. Thus the biochemical actions underlying memory did not arise specifically to support memory…Science has found surprisingly few proteins that are truly unique to the human brain and no signaling systems that are unique to it.

I discovered that cAMP second-messenger signaling is also turned on by serotonin during sensitization….In 1976, we injected cAMP directly into a sensory cell of Aplysia and found that it dramatically increased the amount of glutamate release and, therefore, the strength of the synapse…We injected protein kinase A directly into a sensory neuron and found that it does exactly what cAMP does—it strengthens the connection…In 1980 [lab partner Steven Siegelbaum] discovered one of the targets of cAMP and protein kinase A: a potassium ion channel in sensory neurons that responds to serotonin. Steven found that he could cause it to close either by applying serotonin to the outside of the cell membrane or by applying cAMP or protein kinase A to the inside…When it is closed, potassium ions move out of the cell [after the cell fires] less rapidly, slightly increasing the duration of the impulse…which allows more time for calcium to flow in…which increases the release of glutamate. In addition, cAMP and protein kinase A directly [promote glutamate] synaptic vesicles.