Closed-loop modulation of remote hippocampal representations with neurofeedback

SUMMARY Humans can remember specific remote events without acting on them and influence which memories are retrieved based on internal goals. However, animal models typically present sensory cues to trigger memory retrieval and then assess retrieval based on action. Thus, it is difficult to determine whether measured neural activity patterns relate to the cue(s), the memory, or the behavior. We therefore asked whether retrieval-related neural activity could be generated in animals without cues or a behavioral report. We focused on hippocampal “place cells” which primarily represent the animal’s current location (local representations) but can also represent locations away from the animal (remote representations). We developed a neurofeedback system to reward expression of remote representations and found that rats could learn to generate specific spatial representations that often jumped directly to the experimenter-defined target location. Thus, animals can deliberately engage remote representations, enabling direct study of retrieval-related activity in the brain.