How Memory Is Stored

When you look up a phone number, the digits are coded as patterns of nerve impulses flowing around in a group of neurons. As long as the encoded numbers are “on-line” like this, your memory has access to the numbers.

But what if you start thinking about something else before you dial? Those neurons now have been recruited for another purpose and no longer carry the original number encoding. So you have to look up the number again.

But if the on-line activity goes on long enough, your memory of the number encoding can become stored permanently. How does that happen? Evidence indicates that new learning, as it becomes stored permanently causes new junctions (synapses) to be formed in the neurons of the circuit that originally encoded the information. You can even see physical signs in the form of new growths, called spines, on the nerve fiber terminals.

But what creates these new spines and their functional connections? This involves new RNA and protein synthesis. This in turn requires some genes to be activated to manufacture and maintain the new spines. There are apparently memory genes that are activated by nerve impulse activity. Gene activation is typically driven by specific regulatory proteins, and one such activity-dependent regulatory protein is called CREB.

For a short UTube video on gene expression, click here.

Formation of long-term memory first requires nerve impulse activation of the compound, cyclic AMP. The early studies on CREB were done in different labs, one of which used the mollusc, Aplysia, and the other using the fruit fly. So what does activated AMP do? One of the things is that it binds to a pre-existing protein (called protein kinase), causing part of the protein’s subunits to be liberated. The liberated components move to the neuron’s nucleus, where they bind to another protein, called CREB. Activated CREB then binds to the memory genes, switching them on.

Most recently, another activity-dependent memory gene activator has been discovered called Npas4. This one is especially important because it exists in mammals (mice were the experimental animal) and because it occurs in the hippocampus, the part of the brain necessary to form explicit long-term memories. Moreover, this protein regulates many well-known activity-regulated genes, which suggests that Npas4 might be a “master” control protein. In the study, Npas4 emerged in response to a contextual learning task. A knock-out gene strain of mice that had no Npas4 were poor at learning this task, and the deficit was restored by reversing the Npas4 knockout.

Research on drugs affecting activity-dependent gene regulator proteins is exciting, and may lead to a memory pill. In the meanwhile, the best you can do for your memory is to provide learning situations where original encoding is preserved intact long enough for these gene activation processes to be accomplished.

Sources:

1. Kandel, Eric R. (2005), "The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses", Bioscience Reports 24 (4–5): 475–522, doi:10.1007/s10540-005-2742-7, PMID 16134023

2. Ramamoorthi, K. et al. (2011). Npas4 regulates a transcriptional program in CA3 required for contextual memory formation. Science. 334: 1669-1675.