In Search of Memory: The Emergence of a New Science of Mind

by Eric R. Kandel

short-term, homosynaptic into long-term, heterosynaptic change. In mice those neurons release dopamine, a neurotransmitter commonly recruited in the mammalian brain for attention and reinforcement. Like serotonin in Aplysia, dopamine prompts a receptor in the hippocampus to activate an enzyme that increases the amount of cyclic AMP. However, an important part of the increase in cyclic AMP in the mouse hippocampus occurs in the postsynaptic cell, whereas in Aplysia the increase occurs in the presynaptic sensory neuron. In each case, the cyclic AMP recruits protein kinase A and other protein kinases, which leads to the activation of CREB and the turning on of effector genes. One of the striking things we had found in studying memory in Aplysia was the existence of the memory-suppressor gene that produces the CREB-2 protein. Blocking the expression of that gene in Aplysia enhances both the strengthening and the increase in number of synapses associated with long-term facilitation. In the mouse, we found that blocking this and similar memory-suppressor genes enhances both long-term potentiation in the hippocampus and spatial memory.