Engrams are ensembles of cells that encode, store, and retrieve memories.1 Although conceptualized in the 1900s, scientists struggled to demonstrate their existence, but technological advances help shine a light on the elusive engram.2 Sheena Josselyn, a neuroscientist at the Hospital for Sick Children, uses optogenetics to study engrams.

     Photo of Sheena Josselyn
Looking to the future, Sheena Josselyn, a neuroscientist at the Hospital for Sick Children, said that she is excited to explore engram stability over time, memory orchestration across multiple brain regions, and factors that affect the quality of a memory.
Sheena Josselyn

How does an engram form?

We hypothesized that engrams selectively recruit more excitable cells. To test this, we infected a random population of neurons in the mouse hippocampus with a viral vector that expresses both excitatory and inhibitory opsins that respond to different wavelengths of light.3 This enabled us to turn the same cells on or off throughout an experiment. 

Shortly before we trained mice to associate a context with an aversive foot shock, we activated these cells with light to nudge them into an excitable state. Then to label the memory engram, we used another approach that fluorescently tags cells activated during the behavioral task. Under the microscope, we saw an overlap in fluorescence, suggesting that optogenetically activating the neurons biased them towards becoming part of the memory engram. One day later, we optogenetically silenced the engram during a memory retrieval task and observed a big memory deficit. 

How have optogenetic tools advanced memory research?

Optogenetics has been a game changer. It allows us to answer questions we’ve been dreaming about for years. Newer opsins facilitate more sophisticated experiments that answer these questions in finer detail. We’ve used new optogenetic tools to explore rewarding and false memories and the linking and generalization of memories occurring close in time.4-7

This interview has been edited for length and clarity. 

  1. Josselyn SA, et al. Nat Rev Neuro. 2015;16(9):521-534.
  2. Josselyn SA, et al. J Neurosci. 2017;37(18):4647-4657.
  3. Ramsaran AI, et al. Science. 2023;380(6644):543-551.
  4. Park A, et al. Neuropsychopharmacology. 2022;48(5):724-733.
  5. Lau JMH, et al. Neurobiol Learn Mem. 2020;174:107284.
  6. Rashid AJ, et al. Science. 2016;353(6297):383-387.
  7. Jung JH, et al. Cell Rep. 2023;42(12):113592.