In this project we explore question of how the information replayed during the SPW-R is represented, how and in which sub-networks this information may get encoded during learning, and the molecular and network mechanisms that lead to storage of information at hippocampal synapses. Project 3.1 seeks to develop a method for artificially inducing a memory using new optogenetic methods that allow small groups of neurons to be excited in awake behaving animals. A measure of success will be if the artificial memory is replayed during a SPW-R. The value of such a system will be that it will provide a controlled system for studying the biophysics of memory encoding. Project 3.2 seeks to erase a behaviorally encoded memory. Recent work suggests that memory is stored synaptically by the abundant synaptic protein, CaMKII. This work was based on the ability of dominant negative CaMKII to erase conditioned place avoidance. We will test whether dominant negative CaMKII in CA3 or DG can erase the ability of hippocampal system to replay a memory during the SPW-R. Project 3.3 explores the question of how spatial information is represented in memory. One view is that spatial memory is represented as a continuous path. We will test the alternative hypothesis that memory can be represented selectively by reward sites. Project 3.4 takes advantage of recent advances in long-term optical recording of identified cells. This will allow us to make the first observation of the long-term stability of the stored sequence content replayed during SPW-Rs, as well as longitudinally identifying the network elements associated with this long-term replay, thereby providing important insight into the mechanisms of consolidation.
