Figure 1.

Permanent and stochastic editing of pattern memories in planaria. (a) Planarian mid-body fragments after head and tail amputation regenerate into two-headed worms if exposed to octanol (8OH), a blocker of the electrical synapses known as gap junctions (GJ). Remarkably, such worms go on to regenerate as two-headed worms in future rounds of amputation, in plain water, with no further treatment [30]. These animals can be re-set back to normal by exposure to the proton-potassium ion pump blocker SCH28080, because the pattern memory is stored via stable state of the bioelectric circuit [20,31]. Together these data show how the target morphology (the anatomy to which an animal will regenerate) can be permanently re-written without genomic editing [32]. (b) The penetrance of the gap junction blocker is about 30%—the rest of the animals regenerate as one-headed. However, they are not normal—recutting them in water results in the same 30%/70% proportion of two-headed worms and worms with a destabilized (stochastic) anatomy, as opposed to truly wild-type worms' 100% normal (one-headed) regeneration [31]. This stochastic decision is made independently, as each piece of a worm can have an independent headedness fate. (c) The transition diagram for the bioelectric pattern memory editing: a wild-type worm treated with GJ blocker can become Cryptic (destabilized) or two-headed. The Cryptic state can perpetuate but once a worm becomes two-headed, it always gives rise to two-headed worms. Both Cryptic and two-headed worms can be re-set to normal by SCH28080 treatment. wt, wild-type; 8-OH, octanol; DH, double-headed; CRPT, Cryptic (destabilized target morphology).