The memory function of SPW-Rs depends critically on rapid sequential replay of memory items (e.g. spatial positions along an explored path). The question of how neural networks can produce accurate sequencing is an unsolved problem in neuroscience. Whereas Project 1 deals with the question of how SPW-Rs are initiated, Project 2 deals with how memory sequences are produced. Critical to this project is the need to determine the firing patterns of pyramidal cells and each of the major interneuron types during SPW-Rs. A large number of powerful new optical methods will be used to obtain this data. A second class of experiments will use optogenetic inactivation methods to determine whether the sequencing operation can be produced by events in CA2/CA3 alone, or whether the dentate gyrus (DG) can also influence SPW-R content. We further hope to reveal the basis of important discretization processes that govern SPW-R-related memory sequencing. There have been indications that memory readout during SPW-Rs is discretized by gamma oscillations - in Project 2, we will attempt to verify this and shed light on the basis of this timing operation. Other experiments will provide information relevant to understanding SPW-R termination processes. Collectively, this information, in conjunction with the analysis and simulations proposed in Project 5, is likely to answer fundamental questions about the cellular and network mechanisms governing the recruitment and sequencing of memory content during SPW-R-related replay.
