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

Weeden CS, Morris AM, Rossi CA, Roberts JM, Kesner RP (2010) The role of GABA-ergic interneurons in CA1 and dentate gyrus for sequence learning. Neuroscience 2010 Abstracts 99.26/KKK12. Society for Neuroscience, San Diego, CA.

Summary: The hippocampus (HPP) plays an important role in temporal and spatial memory. Lesion investigations of the CA1 region of HPP indicate the region’s importance in temporal processing and lesions of the dentate gyrus (DG) demonstrate an important role in spatial processing. It has been suggested that a subset of GABAergic interneurons that express Substance P mediate the inhibition of pyramidal and granule cells, which further affects the pattern of their output. This synchronizing action may directly affect information processing of CA1 pyramidal and DG granule cells. A form of temporal processing involves learning specific sequences of events for spatial locations, which incorporates both temporal and spatial qualities attributed to CA1 and DG, respectively. In order to investigate whether interneurons mediate CA1 and DG processing of newly learned locations of sequential patterns, Long-Evans male rats were randomly assigned to the following surgical groups: CA1 pyramidal cell (ibotenic acid), CA1 interneuron (peptidase-resistant substance P analog conjugated to the neurotoxin saporin) (SSP-Saporin), DG granule cell (colchicine), DG interneuron (SSP-Saporin) lesions and controls (PBS). Following recovery from surgery, rats were tested on a sequential learning task for spatial locations using an eight-arm radial maze. Six arm locations were pseudo-randomly assigned to a sequence; each of the arms was baited with a food reward. Doors remained closed until the rat oriented in front of the correct door in the sequence, at which time the door was opened and the rat was allowed access to the reward; the choice was scored as a correct response. However, if the rat oriented to an incorrect door in the sequence, the choice was scored as incorrect and the animal was allowed to reorient to the correct door. The same sequence was repeated ten times per day for a total of ten consecutive days. The percentage of correct choices per day was compared across all ten days. The results indicate that subjects with CA1 pyramidal cell, CA1 interneuron, and DG interneuron, but not DG granule cell lesions, had difficulty acquiring the sequential task when compared to controls. These results suggest an important role for CA1 pyramidal cells, and for interneurons in both CA1 and DG subregions of the HPP in temporal processing of spatial locations.

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