Generation of a Synthetic Memory Trace

Adding Artificial Associations In the mammalian cortex, there is significant spontaneous neural activity that is internally generated, rather than arising from sensory inputs, and this activity influences the processing of natural sensory stimuli. What role does this internally generated activity play in forming and accessing new memory representations? Using transgenic mice combined with controlled artificial activation of widely distributed neuronal ensembles associated with specific contexts, Garner et al. (p. 1513; see the Perspective by Morris and Takeuchi) investigated how spontaneous neuronal activity is integrated into a given context representation. Animals underwent fear conditioning in two distinct contexts. When a circuit in one context was artificially activated during fear conditioning in a separate context, a so-called “hybrid” memory was formed. This artificially stimulated network became a necessary component of the memory trace. These results are consistent with the emerging view that internally generated brain activity is not noise, but a coherent representation that can be incorporated into new associations and memories. The brains of transgenic mice incorporate experimentally generated neural activity into a memory trace. We investigated the effect of activating a competing, artificially generated, neural representation on encoding of contextual fear memory in mice. We used a c-fos–based transgenic approach to introduce the hM3Dq DREADD receptor (designer receptor exclusively activated by designer drug) into neurons naturally activated by sensory experience. Neural activity could then be specifically and inducibly increased in the hM3Dq-expressing neurons by an exogenous ligand. When an ensemble of neurons for one context (ctxA) was artificially activated during conditioning in a distinct second context (ctxB), mice formed a hybrid memory representation. Reactivation of the artificially stimulated network within the conditioning context was required for retrieval of the memory, and the memory was specific for the spatial pattern of neurons artificially activated during learning. Similar stimulation impaired recall when not part of the initial conditioning.