It’s easy to marvel at wonderful architecture, beautiful paintings, complex physics, maybe even a friend’s mind boggling calculus homework. We marvel at great feats of the human mind, yet often overlook the actual mechanics of it; how do we think, where does creativity come from, how are thoughts, how is this very sentence you are reading stored in your brain in such a way it can be recalled, examined and kept, if only for the short term? After all, if the human body is simply a collection of molecules, what is the molecular basis of memory?
Recent experiments by scientists Craddock, Tuszynski and Hameroff from the University of Alberta and University of Arizona have demonstrated a practical mechanism for the encoding of memory in our 1.5kg lumps of grey matter. Memory storage is associated with strengthened synaptic connections. Synapses are the gaps between neurons which help control the passage of information in the brain in the form of electrical activity. Electrical signals known as action potentials are transmitted across synapses via chemicals known as neurotransmitters. Sensory input from the outside world is elegantly converted into action potentials, which the brain can process and produce further action potentials in turn to stimulate a response, whether a muscular movement, an emotion or a memory.
One of the major mechanisms underlying memory is called long-term potentiation (LTP), a process first discovered in 1966 by Norwegian scientist Terje Lømo. LTP works to strengthen synapses through repetitive stimulation of the neuron before the synapse (pre-synaptic) increasing the sensitivity of the neuron after the synapse (post-synaptic). This produces a lasting (hence long term) enhancement of the communication between neurons. Generally changes in synaptic connections are attributed to changes in post-synaptic neurotransmitter receptors and ion channels (which control action potentials). However, receptors and channels are simply transient proteins, while memories can last a lifetime. This suggests more permanent, molecular changes, the mechanism of which has now been brought to light.
During LTP, an enzyme thankfully shortened to CaMKII acts on various molecules, including microtubules (MTs), protein filaments composed of tubulin units, vital to cell transport, organisation and movement. When activated, CaMKII extends six foot-like domains which each phosphorylate (add a phosphate group to) a given substrate. Craddock, Tuszynski and Hameroff found the size and geometry, as well as more complex chemical interactions, of these domains fit precisely with the two possible lattice structures of MTs. They quantified the potential storage capacity; at the simplest case, a tubulin unit can either be phosphorylated or not, and as there are six domains, there are 26, or 64, possible states. Taking into account different types of tubulin and organisation of lattices gives up to 5,281 unique states, and as there are 1019 tubulins in the brain, the brain is akin to an incomprehensibly huge hard drive.
The scientists then explored the possible mechanisms by which MT reorientation regulates synaptic connections, which includes further conformational changes, different types of proteins and electro-mechanical vibrations. Although information processing involves further complex, intricate processes, it can be appreciated that memories are constructed at a minuscule, molecular level. It’s definitely something to marvel at.