UNIQUE DEFICITS IN PLACE CODING ACROSS SUBFIELDS OF THE HIPPOCAMPUS IN A MOUSE MODEL OF TEMPORAL LOBE EPILEPSY.

Abstract

Structured AbstractO_ST_ABSObjectiveC_ST_ABSMemory problems are comorbid with Temporal Lobe Epilepsy (TLE). Animal models of TLE reveal impairments in spatial firing fields of hippocampal place cells, providing a potential neural substrate for memory problems. Each subfield of the hippocampus carries out unique aspects of spatial memory, yet little is known about how individual subfields are perturbed. Here, we investigated the spatial coding properties of the three major subfields of the hippocampus. MethodsSingle unit recordings were made from CA1, CA3 and the dentate gyrus (DG) of mice (N = 10, 6M/4F) induced with epilepsy using the supra-hippocampal kainate model and in control mice injected with saline (N = 6, 3M/3F). Place cell activity was measured while mice foraged in highly familiar environments to assess basic place cell properties and in novel environments to assess remapping. ResultsA lower percentage of cells were classified as place cells in CA1 of epileptic mice, whereas percentages were similar in CA3 and DG compared to control. Place fields of CA1 were less coherent, place fields of CA3 were less stable, and place fields in DG has smaller differences between in-field and out of field firing. All regions constructed new distinct maps within the first session of exposure to a novel environment, however new maps in CA3 trended toward instability. SignificanceThese results point to specific deficits within subfields of the hippocampus, which may indicate that there are different cellular and network mechanisms at play. Such heterogeneity would be predicted to contribute differently to memory deficits. Key PointsO_LICA1 exhibits place map quality problems; CA1 has fewer place cells and those remaining have reduced spatial coherence C_LIO_LICA3 exhibits place map stability problems; CA3 has lower spatial correlation within sessions and trends toward not forming stable new maps in a novel environment. C_LIO_LIDG exhibits reduced signal to noise; DG has smaller differences between in-field and out of field firing rates. C_LI