Place navigation in the Morris water task results in greater nuclear Arc mRNA expression in dorsal compared to ventral CA1

Abstract

Previous work has shown that the dorsal hippocampus has greater activity than ventral regions during place navigation. Exposure to a novel context has also been found to increase hippocampal activation, possibly due to increased spatial demands. However, activation patterns in dorsal and ventral regions have not been investigated in the Morris water task (MWT), which remains the most popular assay of place memory in rodents. We measured activity in a large population of neurons across the CA1 dorsal–ventral axis by estimating nuclear Arc mRNA with stereologic systematic‐random sampling procedures following changes to goal location or spatial context in the MWT in rats. Following changes to goal location or spatial context in the MWT, we did not find an effect on Arc mRNA expression in CA1. However, Arc expression was greater in the dorsal compared to the ventral aspect of CA1 during task performance. Several views might account for these observed differences in dorsal–ventral Arc mRNA expression, including task parameters or the granularity of representation that differs along the dorsal–ventral hippocampal axis. Future work should determine the effects of task differences and required memory precision in relation to dorsal–ventral hippocampal neuronal activity.

Behaviour-drivenArcexpression is greater in dorsal than ventral CA1 regardless of task or sex differences

“…A three-way ANOVA of estimated DAPI and Arc populations across CA1 showed significant effects of label ( F (1,20)=1281, p <0.0001) and sex ( F (1,20)=7.023, p =0.0154), but no effect of task ( F (1,20)=0.08018, p =0.7800), label x sex ( F (1,20)=2.203, p =0.1533), task x sex ( F (1,20)=0.1407, p =0.7115), task x label ( F (1,20)=0.5850, p =0.4533), or task x sex x label interaction ( F (1,20)=0.7562, p =0.3948). Notably, our DAPI estimates closely resemble previous reports of cell number across CA1 (mean DAPI = 418,313) using a design-based stereological approach [9, 21]. Following transformation of population estimates into Arc :DAPI recruitment probability, a two-way ANOVA showed no effect of task ( F (1,20)=0.08314, p =0.3727), sex ( F (1,20)=3.083, p =0.0944), or task x sex interaction ( F (1,20)=0.7737, p =0.3895) on recruitment probability when the entire CA1 population was considered.…”

“…We estimated DAPI and Arc populations across CA1, including dorsal (anterior to -3.8 mm AP from bregma) and ventral (posterior to -5.2 mm from bregma) subregions, and transformed these estimates into a single Arc:DAPI metric of cellular recruitment probability. A three-way ANOVA of estimated DAPI and Arc populations across CA1 showed significant effects of label B) Estimated populations of DAPI and Arc across CA1 in males and females were similar previous studies using design-based stereology in the rat hippocampus [9,21]. C) Following estimation of DAPI and Arc populations, estimates were transformed into Arc:DAPI recruitment probabilities for the entire CA1 population.…”

“…Work on cellular activation during open field navigation has demonstrated recruitment probability is greater in dorsal than ventral hippocampal subfields CA1-3 and the dentate gyrus [7]. A similar gradient of activity was also reported in dry-land spatial memory tasks and, recently, we found the same effect on activation in CA1 with the IEG Arc during memory-guided navigation in the Morris Water Task (MWT) [8][9][10]. Several groups have also reported that contextual fear conditioning augments Arc expression in dorsal and ventral hippocampal subfields and is necessary for contextual fear memory [11][12][13][14].…”

“…A) Randomly chosen example images of DAPI and Arc labelling in dorsal and ventral CA1 in male and female animals that performed the MWT or CFD. B) Estimated populations of DAPI and Arc across CA1 in males and females were similar previous studies using design-based stereology in the rat hippocampus [9, 21]. C) Following estimation of DAPI and Arc populations, estimates were transformed into Arc :DAPI recruitment probabilities for the entire CA1 population.…”

“…The methods used for Arc visualization with FISH are identical to those in our previous report on Arc mRNA expression in the MWT [9]. Arc riboprobes were designed to detect intronic mRNA sequences, and thus nuclear rather than cytoplasmic expression.…”