Hippocampal inactivation during rearing on hind legs impairs spatial memory

Abstract

Spatial memory requires an intact hippocampus. Hippocampal function during epochs of locomotion and quiet rest (e.g., grooming and reward consumption) has been the target of extensive study. However, during navigation rats frequently rear up onto their hind legs, and the importance of hippocampal activity during these periods of attentive sampling for spatial memory is unknown. To address this, we tested the necessity of dorsal hippocampal activity during rearing epochs in the study phase of a delayed win-shift task for memory performance in the subsequent test phase. Hippocampal activity was manipulated with closed-loop, bilateral, optogenetic inactivation. Spatial memory accuracy was significantly and selectively reduced when the dorsal hippocampus was inactivated during rearing epochs at encoding. These data show that hippocampal activity during periods of rearing can be important for spatial memory, revealing a novel link between hippocampal function during epochs of rearing and spatial memory.

Figure 1

Overview of the experimental paradigm. (a) A delayed-win-shift task was used. In the study phase, 4 doors opened and the rats foraged for rewards in the open arms. In the delay phase, the rat was removed from the maze for 4 min. and the maze was cleaned. In the test phase, all 8 doors opened and rats foraged for the remaining rewards. (b) Photograph of radial arm maze and layout of distal cues surrounding the maze. (c) Dorsal hippocampus was targeted with viral infusions and optical fiber implants. (d) Immunofluorescence labeling EYFP expression induced in the dorsal hippocampus. Scale bar is 1 mm. (e) Three optogenetic stimulation conditions were used. Top: Black line plots a hypothetical trace of a rat's height over time. Grey zones mark rearing events, when the rat's height crosses a fixed threshold (dashed line). Off: A control condition wherein no optogenetic stimulation occurred. Rear: The laser is activated (orange rectangle) during rearing events. Delay: The laser is activated based on rearing but the onset and offset occur with a fixed 6 s delay as indicated by the horizontal arrow.

Figure 2

Optogenetic inactivation of dorsal hippocampus during rearing impairs spatial memory. (a) Effect of optogenetic inhibition on the percent correct measure across experimental and control groups. (b) Effect of optogenetic inhibition on number of arm entries during test across experimental {opsin + reporter} and control group {reporter only}. *P < 0.05; ***P < 0.001; mean ± SEM n = 6, experimental group; n = 7, control group.