Behavior-driven arc expression is reduced in all ventral hippocampal subfields compared to CA1, CA3, and dentate gyrus in rat dorsal hippocampus

Abstract

Anatomical connectivity and lesion studies reveal distinct functional heterogeneity along the dorsal-ventral axis of the hippocampus. The immediate early gene Arc is known to be involved in neural plasticity and memory and can be used as a marker for cell activity that occurs, for example, when hippocampal place cells fire. We report here, that Arc is expressed in a greater proportion of cells in dorsal CA1, CA3, and dentate gyrus (DG), following spatial behavioral experiences compared to ventral hippocampal subregions (dorsal CA1 = 33%; ventral CA1 = 13%; dorsal CA3 = 23%; ventral CA3 = 8%; and dorsal DG = 2.5%; ventral DG = 1.2%). The technique used here to obtain estimates of numbers of behavior-driven cells across the dorsal-ventral axis, however, corresponds quite well with samples from available single unit recording studies. Several explanations for the two- to-threefold reduction in spatial behavior-driven cell activity in the ventral hippocampus can be offered. These include anatomical connectivity differences, differential gain of the self-motion signals that appear to alter the scale of place fields and the proportion of active cells, and possibly variations in the neuronal responses to non-spatial information within the hippocampus along its dorso-ventral axis.

Figure 1

Diagrams of coronal sections taken from a rat brain atlas (Paxinos and Watson, 1998). (A) Depicts approximate regions of the dorsal (~Bregma 3.2 to 4.5) and (B) more ventral hippocampus regions (~Bregma 4.8 to 6.0) that were studied.

Figure 2

(A) The proportion of Arc mRNA-positive cells is significantly higher in dorsal CA1 pyramidal cells (32% +/− 1.5) compared to more ventral CA1 pyramidal cells (13% +/− 0.9). (B) Representative confocal images from dorsal and (C) more ventral CA1 hippocampal subregions, respectively. Calibration bar = 20 µm. Cell nuclei are counterstained with Sytox shown here in green and Arc mRNA-positive transcription foci are in red. The insets in B and C show a magnified view of the Arc transcription foci in CA1 pyramidal cells in the dorsal and more ventral areas respectively. The white arrows correspond to the same cell in the main image and the magnified image.

Figure 3

(A) The proportion of Arc mRNA-positive cells is significantly higher in dorsal CA3 pyramidal cells (22% +/− 1.8) compared to more ventral CA3 pyramidal cells (8.1% +/− 0.9). (B) Representative confocal images from dorsal and (C) ventral CA3 hippocampal subregions, respectively. Calibration bar = 20 µm. Cell nuclei are counterstained with Sytox shown here in green and Arc mRNA positive Foci are in red. The insets in B and C show a magnified view of the Arc transcription foci in CA3 pyramidal cells in the dorsal and more ventral areas respectively. The white arrows correspond to the same cell in the main image and the magnified image.

Figure 4

(A) The proportion of Arc mRNA-positive granule cells is significantly higher in the suprapyramidal blade (SPB) of dorsal dentate gyrus following exploratory behavior (2.5% +/− 0.2) as compared to the suprapyramidal blade of the ventral dentate gyrus (1.2% +/− 0.1). (B) Confocal images taken from the dorsal and ventral suprapyramidal blades of the dentate gyrus (left panels) and infrapyramidal blades of the dentate gyrus (right panels). A significant difference was observed between behavior-treated animals and caged control rats in the suprapyramidal blade of dentate gyrus. No significant difference was observed between behavior-treated animals and caged control rats in the infrapyramidal blade (IPB) of dentate gyrus. Calibration bar = 20 µm. Arc mRNA- positive cells are shown in red and granule cell nuclei are counterstained with Sytox, shown in blue. The insets in B show a magnified view of the Arc transcription foci in granule cells in the dorsal and more ventral areas respectively. The white arrows correspond to the same cell in the main image and the magnified image.