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The hippocampus and related medial temporal lobe structures (entorhinal cortex, perirhinal cortex, etc.) play a vital role in transforming experience into long-term memories that are then stored in the cortex, however the cellular mechanisms which designate single neurons to be part of a memory trace remain unknown. Part of the difficulty in addressing the mechanisms of transformation of short-term to long-term memories is the distributed nature of the resulting “engram” at synapses throughout the cortex. We therefore used a behavioral paradigm dependent on both the hippocampus and neocortex that enabled us to generate memory traces rapidly and reliably in a specific cortical location, by training rodents to associate the direct electrical microstimulation of the primary sensory neocortex with a reward. We found that medial-temporal input to neocortical Layer 1 (L1) gated the emergence of specific firing responses in subpopulations of Layer 5 pyramidal neurons marked by increased burstiness related to apical dendritic activity. Following learning and during memory retrieval, these neocortical responses became independent of the medial-temporal influence but continued to evoke behaviour with single bursts sufficient to elicit a correct response. These findings suggest that L1 is the locus for hippocampal-dependent associative learning in the neocortex, where memory engrams are established in subsets of pyramidal neurons by enhancing the sensitivity of tuft dendrites to contextual inputs and driving burst firing. Zoom link to join- https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09 Meeting ID: 966 0803 3618 Password: 564068 Host: Dr. Rita Schmidt rita.schmidt@weizmann.ac.il tel: 9070