Communication between synapse and nucleus

Memories can form virtually instantaneously, and can last for a lifetime. The extreme rapidity of memory formation suggests that gross physical changes in the brain are not involved--but paradoxically, the extreme stability of memories suggests that a physical change of some kind must be taking place. Somehow, fleeting bursts of electricity in the brain must have a way to cause rapid but permanent changes. An interesting analogy may exist between memory formation in neurons and differentiation of proliferating cells--perhaps in neurons, communication of even ephemeral external information from the surface membrane to the nucleus leads to stable changes in gene expression, and consequent stable changes in physiological properties underlying memory formation.; The bulk of the information a neuron receives comes through its synapses--the devices for transmitting electrical information from cell to cell. We therefore reasoned that communication between the synapse and the nucleus is very likely to be important in memory formation. We studied activation of a nuclear transcription factor (CREB--known from genetic work in mammals and flies to be important in long-term memory), and we employed a combination of electrophysiology, immunocytochemistry, imaging, pharmacology, biochemistry, and neuronal transfection to monitor and manipulate biochemical events leading up to and following CREB activation. The signaling has turned out to be more interesting and more cleverly designed than we had imagined, and we actually obtained clues to the purpose of the overall signaling pathway from knowledge about the molecular details of its structure. Our findings suggest that CREB acts as a switch under the bidirectional control of multiple elegantly-designed activity-dependent signaling pathways, and that memory formation at the level of a single neuron seems to involve an extraordinarily rapid pathway which responds to the duration of incoming bursts of electrical activity. This finding may represent a possible molecular mechanism for the selection of only certain events or ideas for consolidation into long-term memories, and may be a significant step toward an understanding of the molecular genetic basis of brain function.