Examining memory linking and generalization using scFLARE2, a temporally precise neuronal activity tagging system
Jung Hoon Jung,
Ying Wang,
Asim J. Rashid,
Tao Zhang,
Paul W. Frankland,
Sheena A. Josselyn
Affiliations
Jung Hoon Jung
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
Ying Wang
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Asim J. Rashid
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
Tao Zhang
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
Paul W. Frankland
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 3G3, Canada; Child & Brain Development Program, Canadian Institute for Advanced Research (CIFAR), Toronto, ON M5G 1M1, Canada
Sheena A. Josselyn
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 3G3, Canada; Corresponding author
Summary: How memories are organized in the brain influences whether they are remembered discretely versus linked with other experiences or whether generalized information is applied to entirely novel situations. Here, we used scFLARE2 (single-chain fast light- and activity-regulated expression 2), a temporally precise tagging system, to manipulate mouse lateral amygdala neurons active during one of two 3 min threat experiences occurring close (3 h) or further apart (27 h) in time. Silencing scFLARE2-tagged neurons showed that two threat experiences occurring at distal times are dis-allocated to orthogonal engram ensembles and remembered discretely, whereas the same two threat experiences occurring in close temporal proximity are linked via co-allocation to overlapping engram ensembles. Moreover, we found that co-allocation mediates memory generalization applied to a completely novel stimulus. These results indicate that endogenous temporal evolution of engram ensemble neuronal excitability determines how memories are organized and remembered and that this would not be possible using conventional immediate-early gene-based tagging methods.
