Title: Manipulating memory traces in the hippocampus
Abstract: Since the discovery of patient H.M., researchers have known that the hippocampus is important for memory. Subsequent animal work reinforced this finding by showing that hippocampal dysfunction produces profound amnesia for spatial and contextual information. Despite these well-established facts, it is still unclear why the hippocampus is so fundamental for memory. The dominant idea, based on the work of Marr, is that memory is retrieved when the hippocampus reinstates patterns of cortical activity that were observed during learning. This idea is supported by spatial studies in rodents showing that learned sequences are replayed in the hippocampus and cortex after training. However, it has not been determined if reactivation of cortical representations during replay (or memory retrieval) requires the hippocampus. To examine this idea, my lab uses fos-tTA mice to tag active hippocampal neurons with the long-lasting fluorescent protein H2B-GFP and light sensitive opsins. These proteins allow us to identify 'encoding neurons' several days after learning and manipulate their activity with laser stimulation. When tagged hippocampal neurons are silenced, we find that memory retrieval is impaired and representations in the cortex and amygdala cannot be reactivated. Memory retrieval is also induced when tagged cells are stimulated, but only under certain conditions. These data are consistent with the idea that the hippocampus retrieves memory by reinstating patterns of cortical activity that were present during learning.