Search

The structured reactivation of hippocampal neuronal ensembles during fast synchronous oscillatory events termed sharp-wave ripples (SWRs) has been suggested to play a crucial role in the storage and use of memory. Activity in both the CA2 and CA3 subregions can proceed this population activity in CA1 and chronic inhibition of either region alters SWR oscillations. However, the precise contribution of CA2 to the oscillation, as well as to the reactivation of CA1 neurons within it, remains unclear. Here we employ chemogenetics to transiently silence CA2 pyramidal cells in mice and observe that while SWRs still occur, the reactivation of CA1 pyramidal cell ensembles within the events lose both temporal and informational precision. These observations suggest that CA2 activity contributes to the fidelity of experience-dependent hippocampal replay.

mmediate-early gene (IEG) expression has long been a useful tool in deterining the activation history of a neuron (French et al.,2001; Graybiel t al.,1990; Hall et al., 2001; Labiner et al., 1993; Sheng et al., 1993; Thomas t al., 2002). Fluorescent in situ hybridization (FISH) using dual probeswhich tain neuronal intranuclear foci containing the IEGs Arc and Homer1a have llowed the detection of gene expression to also serve as a temporalmetric of hen the cell was active (Vazdarjanova and Guzowski, 2004), facilitating the omparison of neuronal ensembles activated by two experiences separated y about thirty minutes. We have employed this approach to assess patern completion/pattern separation in the mouse hippocampal circuit. The xperimental paradigm consists of two arenas, box A and box B, different n shape, color, floor texture, item content, odor and room location. Animals hat explore the samebox twice are expected to reactivate apreviously active ippocampal ensemble with a high degree of overlap, while exploration of different box during the second session would reactivate ensembles with educed overlap. To investigate the role of CA3 and DG plasticity in the actiation of unique neuronal ensembles, we are using mutant mice lacking the R1 subunit of the NMDA receptor in either CA3 or DG, and their respective ittermate controls. Deficits observed during previously conducted behavoral and physiological experiments suggest a lack of pattern completion in A3-NR1 KOmice, and a lack of pattern separation in DG-NR1 KO. Our study eveals differences between control and mutant mice as well as subregional ifferences within groups.