A small but enthusiastic group of neuroscientists is exhuming overlooked experiments and performing new ones to explore whether cells record past experiences — fundamentally challenging what memory is.
by Claire L. Evans Contributing Writer
In 1983, the octogenarian geneticist Barbara McClintock stood at the lectern of the Karolinska Institute in Stockholm. She was famously publicity averse — nearly a hermit — but it’s customary for people to speak when they’re awarded a Nobel Prize, so she delivered a halting account of the experiments that had led to her discovery, in the early 1950s, of how DNA sequences can relocate across the genome. Near the end of the speech, blinking through wire-framed glasses, she changed the subject, asking: “What does a cell know of itself?”
McClintock had a reputation for eccentricity. Still, her question seemed more likely to come from a philosopher than a plant geneticist. She went on to describe lab experiments in which she had seen plant cells respond in a “thoughtful manner.” Faced with unexpected stress, they seemed to adjust in ways that were “beyond our present ability to fathom.” What does a cell know of itself? It would be the work of future biologists, she said, to find out.
Forty years later, McClintock’s question hasn’t lost its potency. Some of those future biologists are now hard at work unpacking what “knowing” might mean for a single cell, as they hunt for signs of basic cognitive phenomena — like the ability to remember and learn — in unicellular creatures and nonneural human cells alike. Science has long taken the view that a multicellular nervous system is a prerequisite for such abilities, but new research is revealing that single cells, too, keep a record of their experiences for what appear to be adaptive purposes.
In a provocative study published in Nature Communications late last year, the neuroscientist Nikolay Kukushkin and his mentor Thomas J. Carew at New York University showed that human kidney cells growing in a dish can “remember” patterns of chemical signals (opens a new tab) when they’re presented at regularly spaced intervals — a memory phenomenon common to all animals, but unseen outside the nervous system until now. Kukushkin is part of a small but enthusiastic cohort of researchers studying “aneural,” or brainless, forms of memory. What does a cell know of itself? So far, their research suggests that the answer to McClintock’s question might be: much more than you think.
Brainless Learning
The prevailing wisdom in neuroscience has long been that memory and learning are consequences of “synaptic plasticity” in the brain. The connections between clusters of neurons simultaneously active during an experience strengthen into networks that remain active even after the experience has passed, perpetuating it as a memory. This phenomenon, expressed by the adage “Neurons that fire together, wire together,” has shaped our understanding of memory for the better part of a century. But if solitary nonneural cells can also remember and learn, then networks of neurons can’t be the whole story.
From an evolutionary perspective, it makes sense for cells outside a nervous system to be changed by their experiences in ways that encourage survival. “Memory is something that’s useful to all living systems, including systems that predated the emergence of the brain by hundreds of millions of years,” said Sam Gershman (opens a new tab), a cognitive scientist at Harvard University.
Acellular slime molds, foraging for food, lay down chemical traces that remind them where they’ve been. Bacteria compare present and previous conditions as they move through chemical gradients towards more favorable environments. Gershman has a hunch that these “more ancient form[s] of memory” may play an important, complementary role to synaptic plasticity — so much so that he recently added a wet lab to his operation to systematically study the single-celled ciliate Stentor coeruleus...
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