Lecture by Jiyun Shin: The role of Perirhinal feedback input in cortical layer 1 in learning

Two-stage model of memory postulates that newly acquired memories are first encoded in the hippocampus and gradually transferred to the neocortex, where long-term memories are stored. However, cellular mechanisms underlying information transfer to neocortexremain elusive. Here, we show that learning is controlled by specific medial-temporal input to neocortical layer 1. To show this we developed a novel learning paradigm using direct cortical microstimulation, which allowed the precise region of learning to be examined and manipulated. Chemogenetically suppressing the last stage of the medial temporal loop, i.e. perirhinal cortex input to neocortical layer 1, profoundly disrupted early memory formation but had no effect on behavior in trained animals. The learning involved the emergence of a small population of layer 5 pyramidal neurons (~10%) with significantly increased firing involving high-frequency bursts of action potentials, which were also reduced by suppression of perirhinal input. Moreover, we found that dendritic excitability was correspondingly enhanced in a similarly-sized population of pyramidal neurons and suppression of dendritic activity via optogenetic activation of dendrite-targeting inhibitory neurons also suppressed learning. We conclude that the medial temporal input to the neocortex controls learning through a process in L1 that elevates dendritic calcium and promotes burst firing.