Can we understand memories at the molecular level?

When we talk about memories, we immediately associate it with some sort of neural activity. Learning a language includes being exposed to a massive quantity of new information, where our brains try to save as much as it can. But have you ever wondered how does this process happen?

A natural comparison would be to think of our brains as computers that save all the information that they receive. But that doesn’t happen quite often, sometimes we forget what we have learned unless we are actively exposed to it. Then, you might wonder, how do brain cells actually form memories?

Connections between brain cells happen through junctions called synapses. The word synapse comes from the Greek synapsis, meaning “conjunction”. Neurons are always communicating to each other through synapses, and the strengthening of these connections is associated with memory formation through a process called Long Term Potentiation (LTP). 

Synapses are classified in pre- and post- synapses, which correspond to the cell sending the message (pre-synapse) and the cell receiving the message (post-synapse). When a neuron tries to send a message, a change in the membrane voltage occurs. This change induces the release of the amino acid glutamate (the message), which activates a series of proteins located at the recipient cell called glutamate receptors. Once glutamate receptors are turned on, ions such as sodium are able to enter into the post synapse producing a change in postsynaptic membrane voltage. However, sodium itself doesn't trigger any machinery to strength memory formation.  In order to induce memory formation, calcium needs to enter the recipient cell to activate the machinery for LTP. Think about it as glutamate being the message from the pre-synapse and calcium representing the translated message at the post-synapse.  There is one kind of glutamate receptors, which are unique among other receptors because they are the only doors for calcium to get into the post-synapse. These unique receptors are called NMDA receptors and they are the main molecular character involved in memory formation.

The synapse. Communication between neurons occurs through the synapse. NMDA receptors trigger LTP by permeation of calcium.

NMDA receptors are quite peculiar not only because of their calcium permeability, but also because of their role as “coincidence detectors”, since they will only respond when simultaneous events are happening in both sides of the synapse. These two events are: 1) the cell sending the message has to release the glutamate, and 2) a change in the postsynaptic membrane voltage has to happen.  Once these two events occur in the synapse, the connection between the neurons is strengthened. Strengthening and weakening of neuronal bonds is a phenomenon called synaptic plasticity, where regulation of synapse communication represents our memories. Synaptic plasticity is frequently associated with remodeling and growing of new neural connections, which we could translate in terms of how many new words we can memorize while practicing a new language.

Since NMDA receptors are the molecular machinery of our memories, scientists have been interested in them since their classification back in late 1970’s. Studying the shape of these receptors has been useful to understand their mode of activation. Also, it has been found that when these receptors do not function properly they can lead to neurological diseases like Alzheimer’s and Parkinson’s disease. Research has been focused on the design of new drugs to target NMDA receptors involved in brain diseases. As the scientific knowledge advances, scientists understand better the molecular processes that lead to the formation of our memories. Its exciting to think that one day we could control what memories we want to remember based on how our NMDA receptors respond, and therefore being able to learn a new language in a more efficient way than we do today. 

Morris, R.G. (2013). NMDA receptors and memory encoding. Neuropharmacology 74, 32-40

Mayford, M., Siegelbaum, S.A., and Kandel, E.R. (2012). Synapses and memory storage. Cold Spring Harb Perspect Biol 4.