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Authors & Affiliations
Annelies Hoorn, Sungmo Park, Asim Rashid, Paul W. Frankland, Sheena A. Josselyn
Abstract
Memories are encoded by ensembles of neurons (engrams) that are active during learning. Within a given brain region, eligible neurons compete for allocation to an engram and neurons with increased excitability at the time of training are likely to be allocated to the engram. Previous findings show that neurons with increased excitability during training also have increased excitability for ~6h. Here, we examined the temporal dynamics of neuronal excitability important for memory allocation. We focused on the lateral amygdala (LA) and cued fear memory. We expressed both an excitatory and inhibitory opsin in the same sparse, random subset of LA neurons. At different times before fear conditioning, we optically activated this subset of neurons to allocate them to the engram. To examine whether these neurons were critical components of the engram, we tested mice both with and without optical inhibition. We find that stimulation up to 6h, but not 24h before training biases neuronal allocation to the engram. Next, we tested what happens under basal conditions, by labeling endogenously active neurons at different timepoints prior to learning. Single chain FLARE (scFLARE) allowed us to label active neurons at different timepoints prior to learning. We then optically inhibited these neurons during testing, and found that endogenously active neurons 1h, but not 24h prior to learning, encode the memory shown by successful inhibition. Taken together, these findings indicate that excitability in the LA is temporally defined and plays a critical role in neuronal selection to a fear engram.