Kicking off this year’s SfN Presidential Special Lecture series, Dr. Kelsey Martin presented her work exploring the molecular contributions to memory formation. Dr. Martin is a Professor and Chair of the Department of Biological Chemistry at UCLA where she studies how memories are stored in the brain.
In order to better discuss the ideas and findings presented by Dr. Martin, we have decided to cover her talk in a four-part series:
- An introduction to discuss background and research questions
- Evidence for signaling between active synapses and the nucleus
- Distributed or specified distribution? How does mRNA travel to distal synapses?
- Synapse activation regulates protein synthesis
By 1970, it was clear that long-term memory formation relied on protein synthesis . Later studies further confirmed this by showing that long-term potentiation (LTP) is similarly dependent on the generation of new proteins . In hindsight, these findings may not be altogether surprising. However, as is typical of important scientific discoveries, the protein synthesis dependent nature of memory formation spurred further questions and research. In her recent work, Dr. Martin has explored the mechanisms that allow signaling molecules, mRNA, and/or proteins to negotiate the distance between the synapse and nucleus. This research is important for linking the electrical activity that enables memory formation, like LTP, with the cellular and molecular mechanisms that allow protein synthesis to occur.
According to Dr. Martin, there are essentially two broad questions that have to be addressed in order to understand the nature of synapse-nuclear interactions. The simpler of the two revolves around the spatial relationship of distal synapses to the nucleus. In other words: how does the signal, or information, that a synapse has been activated travel to the nucleus and trigger transcription?
Because of the possibility of highly varied dendritic arborization, this distance from can be rather far. In mouse pyramidal cells, for example, dendritic length varies from 200-800 um  – a distance that is 10-40 times further than the diameter of the soma.
The second, more complex, problem is to understand how the product of nuclear activity targets the activated synapse with a high degree of specificity. The protein-dependent LTP and corresponding increase in synaptic strength are synapse specific . Therefore the consequence of nuclear activity cannot have widespread effects.
In the following posts of this series, we will discuss the the experiments that have allowed Dr. Martin and her lab to show 1) how signaling molecules move from distal dendritic synapses to the nucleus and trigger transcription, 2) how this leads to a distribution of mRNA within the cell, and 3) how synapse activation results in synapse-specific translation.
1. Agranoff, B.W., Davis, R.E., Casola, L. & Lim, R. (1967). Science 158, 1600-1601
2. Lynch, M.A. (2004). Long-term potentiation and memory. Pysiological Reviews. 84:1, pp. 87-136.
3. Benavides-Piccione, R., Hamzei-Sichani, F., Ballesteros-Yanez, I., DeFelipe, J., Yuste, R. (2006). Dendritic size of pyramidal neurons differs among mouse cortical regions. Cerebral Cortex, 16:7, pp. 990-1001
4. Martin, K.C. (2014). The living record of memory: Gene, neurons, and synapses. SfN 2014 Presidential Lecture.