The role of GABA-ergic interneurons in CA1 and dentate gyrus for sequence learning

The hippocampus (HPP) is widely accepted as a structure that supports spatial memory. Current interest is focused on temporal processing for sequences of events. It has been demonstrated that HPP lesions disrupt acquisition of a spatial temporal sequence in an 8-arm maze (DeCoteau & Kesner, 2000). •HPP subregions have been indicated to be critical in spatial temporal sequence processing. The CA1 region has been shown to play a critical role in temporal information processing and CA1 principal cell lesions impair acquisition of 8-arm radial maze sequences (Rolls & Kesner, 2006; Weeden et al, 2009). The dentate gyrus (DG) is also an important region in the processing of new spatial information, but granule cell lesion studies indicate that principal cells are not a necessary component in the learning of sequential events (Weeden et al, 2009). •Interneurons exhibit inhibitory control over the excitatory principal cells of HPP (Freund & Buzáki, 1996). Their role in temporal processing for spatial locations has yet to be identified. Electrophysiological recording investigations indicate that CA1 and DG interneurons display differential patterns of activation when engaged in identical tasks, such as novel environment exploration (Nitz & McNaughton, 2004). These divergent patterns suggest unique roles for interneurons of different subregions. Within the HPP, inhibitory interneurons exclusively express Substance P receptors (SPR). SPRs have a high affinity for a peptidase-resistant Substance P analog conjugated to the neurotoxin saporin (SSP-Saporin), which allows for selective neurotoxic lesions of inhibitory interneurons that spare surrounding excitatory principal cells (Martin & Sloviter, 2001). The present study aims to determine the level of influence HPP interneurons of the CA1 and DG subregions exert on acquisition of spatial temporal sequences compared to excitatory principal cells. We predict that CA1 interneuron lesion subjects but not DG lesion subjects will make more errors during acquisition of sequence information compared to controls.