Photo courtesy of Diego PH (Unsplash)
by Daniel Phillips
What are memories made of, and how and where are they stored in our bodies? The basis of what is now the widely accepted answer to these questions was proposed over 100 years ago by Spanish neuroscientist Santiago Ramón y Cajal. His well-known explanation states that experiences are remembered because they leave behind a long-lasting mark on the body in the form of new or modified connections between multiple neurons; the information-processing cells of the nervous system. This view sees that a memory is made from the network of neurons that was modified by some corresponding experience and requires that memories are necessarily located within synapses between neurons. However, this view has potentially been turned on its head by a thought-provoking and sci-fi-esque study published towards the end of last year, which suggested that the memory of learned behaviour in the sea snail Aplysia is stored in chemical form inside single neurons, not between them. Strikingly, the study conducted by David Glanzman’s research laboratory at UCLA revamped a controversial memory-transfer technique devised in the 1960’s that involves isolating chemicals from the nervous system of trained animals and injecting them into untrained ones to test if they ‘contain’ the original learned memory. The memory which Glanzman and his team wanted to transfer was that of a basic form of learning called sensitization, which, for Aplysia, involves the increased sensitivity of a gill-withdrawal reflex in response to being repeatedly shocked. The suspected ‘chemical memory format’, like those earlier studies from the 1960s, but for an altogether different reason, was ribonucleic acid (RNA); DNAs little brother.
The study began by training (“shocking”) many Aplysia for two days to sensitize their withdrawal responses. RNA was then extracted from their neurons and injected into Aplysia that had not been sensitized. After 24-hours injected animals were then also shocked. Animals injected with RNA from non-sensitized Aplysia exhibited a normal withdrawal response, but Aplysia injected with RNA from sensitized animals exhibited a hypersensitive reflex when shocked themselves - suggesting that in the mixture of RNAs from trained Aplysia exists some ‘memory’ of sensitization. Significantly, RNA from sensitized Aplysia even appeared to transfer the memory when injected directly into isolated sensory neurons cultured in a petri dish, because it made them more sensitive to the activating effect of neurotransmitters. The authors interpreted that single neurons are sufficient memory-storage units all by themselves. And in a final experiment, they put all the pieces together by indicating how memory of sensitization is stored in cells and why RNA transfers it to other Aplysia. They repeated the initial experiment - shocking snails, extracting their RNA and injecting it into non-shocked snails - but this time they also injected the animals with a chemical that blocks the activity of the enzyme DNA-methyltransferase, which functions to ‘turn-off’ genes by adding a methyl group to areas required for their activation. This inhibitor blocked the RNA of shocked snails from transferring sensitization to others following injection, and in so doing provided needed clarity for the memory-transfer study phenomenon.
RNA-injections have been known to ‘transfer’ memories of learned behaviours into other animals since the 1960s; sometimes to entirely different species. The discovery of DNA was fresh in peoples’ minds at this time, and the thinking was that just as DNA stores information about a creatures evolutionary history, RNA, the more temporary result of DNA being ‘read-out’, might store information about its life time experiences. The study described here provides a subtler vision of RNA as a ‘memory molecule’. This is that being shocked makes Aplysia sensory cells produce ‘shock-specific’ RNAs, some of which coordinate with DNA-methyltransferase to turn-off one or more genes that make the cells more sensitive to future activation. And, crucially, such targeted silencing is not restricted to the animal of origin. Glanzman’s bizarre study has both theoretical and practical implications. Theoretically, it suggests simple memories exist inside cells as chemical marks made upon DNA in the nucleus. Practically, the authors argue it creates the possibility that memory-based disorders, like PTSD, might be treatable by manipulating a patient’s memories. A sobering caveat, however, is that we are no closer to transferring complex memories - like those acquired by diligent exam preparation - from one individual to another.
