Are memories formed by prions?

(First of two parts)

We still know very little about how our brain works. We don’t know how we think. We don’t know how we analyze and solve problems. We don’t know how we remember. We don’t even know why we forget. 

Let’s consider the question of memory.

It is estimated that we have a hundred, or so, billion nerve cells (neurons) in our brain and that each neuron is connected to several thousand other neurons, giving a total of about a hundred trillion possible neuronal connections (synapses). It is believed that memory is stored in neuronal circuits that are formed by long-lasting synaptic connections.

One can envision neurons to be continually forming transient and loose connections with their neighbors. Once a sensory stimulus is received, the set of neurons which are interacting at that very instant would then form the neuronal circuit associated with the stimulus — to store the memory of that particular stimulus. Repeated stimulation of the same set of neurons will reinforce the connections and form long-lasting memory. Particularly strong stimuli will form strong connections and will be long remembered. Memory loss will occur when a weak stimulus is not repeated, or not repeated often enough.

It sounds so simple. But, in this day and age, we are no longer satisfied with vague inferences. Cellular connections are physicochemical in nature and we have to offer, or at least attempt, a more tangible, preferably a molecular, explanation for the phenomenon of memory. (Many of us may not believe it, but didn’t Linus Pauling say that “Man is simply a collection of molecules” and “can be understood in terms of molecules”?)

But, which molecule(s) do we implicate?

Aha, it could be the prions — those molecules which cause mad-cow disease and a number of human neurodegenerative diseases. The word “prion,” which means “infectious protein,” sends shivers up our spines because the diseases caused by prions are invariably fatal.

Prions are multi-stable proteins that can assume at least two stable conformations: a normal one that is detergent-soluble and is protease-sensitive, and a pathogenic one that is protease-resistant and that forms detergent-insoluble fibrillar aggregates. The fibrillar aggregates are thought to cause the neurodegenerative disorders. The normal biological function of prions is not known, yet the high conservation of the sequences of prions among distantly related animals strongly suggests a common and important function. 

There is increasing evidence that prions are involved in long-term memory. Indeed, animals lacking the prion gene have been shown to have impaired memories. The genetic influence is further highlighted by memory-retention differences observed in individuals with single amino-acid differences in their prion molecules.

It has been suggested that prions, or prion-like molecules, trigger the synthesis and continued production of molecules that are important in memory retention. We disagree. 

(To be concluded)

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Eduardo A. Padlan is a corresponding member of the NAST and is an adjunct professor in the Marine Science Institute, College of Science, University of the Philippines Diliman. Gisela P. Padilla-Concepcion is an academician of the NAST and is a professor in the UP Marine Science Institute. They can be reached at [email protected] and [email protected], respectively.