From synapse to genome: The evolution of Hebb's neurophysiological postulate
Departments of Psychology and Neurobiology, and Neuroscience Institute, Northwestern University, Evanston, Illinois, USA
In The Organization of Behavior Hebb defined, in but 4 succinct lines, 4 key elements that are necessary to modify the synapse to encode for new memories.
- Both presynaptic and postsynaptic processes of the synapse, typically formed by the axon of one cell and the dendrite of another, must fire at about the same time. This temporal contiguity or co-activity requirement leads to a long-lasting modification of those synapses that underlie memory formation. The dissociation of this co-activity more recently in long-term potentiation (LTP) studies has documented the fact that this change is necessary for memory formation.
- The second is that this takes place in specific brain regions… brain localization of function. The role of the hippocampus in memory demonstrated in clinical studies of Scoville and Milner, and the more recent demonstrations with brain imaging, testify to the localized nature of the memory trace.
- The co-activity must be repeated and persistent initially, and then followed by a metabolic event. This was the ‘dual trace’ view of memory formation akin to the perseveration and then memory consolidation view of information storage. Current evidence indeed demonstrates that immediate post-learning manipulations that disrupt memory are ineffective hours later, consistent with this idea. But recently others question whether this is a serial process, suggesting a parallel sequence of events.
- The metabolic event that Hebb chose to focus upon was axonal growth. While he suggested that it might occur in ‘one or both’ cells, current evidence suggests that deleting ‘one or’ would be appropriate. Hebb clearly implied that the axonal terminals, would likely sprout under repeated and persistent activity and would be a most probable way in which to achieve structural change leading to lasting memories. Work from our laboratory has identified a particular gene that may be especially important for this process.
But early in vitro demonstrations of activity-independent synaptogenesis by Stanley Crain and Constantino Sotelo and an abundance of evidence that followed indicated that synapses can form in the absence of activity. Thus, a strong genetic component in determining the formation and sculpting of synaptic connections needs to be taken into account by any comprehensive theory of synaptic growth in the adult. Hebb’s proposal did not encompass the role that genetics might play in determining activity-independent wiring of connections. Cast in another metaphor the current view of synaptic plasticity is one of relative contribution of genetic (nativism) and environmental input (empiricist) determinants. If time permits I will discuss a recent study which demonstrated the relative contribution of a) an input-independent genetic program and b) an input-dependent post-transcriptional regulatory mechanism to axonal growth within the hippocampus.
Session V -- Donald O. Hebb Seminar
Sunday, 27 June 2004, 2:30 - 5:00 pm
Ninth Annual Meeting of the
International Society for the History of the Neurosciences
Montreal, Quebec, Canada