Post-training reversible inactivation of the hippocampus enhances novel object recognition memory

Abstract

Research on the role of the hippocampus in object recognition memory has produced conflicting results. Previous studies have used permanent hippocampal lesions to assess the requirement for the hippocampus in the object recognition task. However, permanent hippocampal lesions may impact performance through effects on processes besides memory consolidation including acquisition, retrieval, and performance. To overcome this limitation, we used an intrahippocampal injection of the GABA agonist muscimol to reversibly inactivate the hippocampus immediately after training mice in two versions of an object recognition task. We found that the inactivation of the dorsal hippocampus after training impairs object-place recognition memory but enhances novel object recognition (NOR) memory. However, inactivation of the dorsal hippocampus after repeated exposure to the training context did not affect object recognition memory. Our findings suggest that object recognition memory formation does not require the hippocampus and, moreover, that activity in the hippocampus can interfere with the consolidation of object recognition memory when object information encoding occurs in an unfamiliar environment.

Figure 1.

Cannulae placement in the dorsal hippocampus. A brain coronal section from a representative mouse showing cannulae placement in the dorsal hippocampus. Brain slices were stained with cresyl violet.

Figure 2.

Post-training dorsal hippocampal inactivation impairs the formation of long-term object-place memory. (A) Schematic representation of the open field and object locations during training and test sessions. (B) Intrahippocampal injections occurred immediately after the training session. Mice that received intrahippocampal saline injections (n = 10) increased the time spent exploring the displaced object while decreasing the time spent exploring the non-displaced object during the test session. In contrast, mice that received intrahippocampal injections with the GABAergic agonist muscimol (n = 9) did not distinguish the displaced from the non-displaced object and slightly increased the time spent on both displaced and non-displaced objects during the test session. (C) Intrahippocampal injections occurred 24 h before the training session. Mice that received intrahippocampal saline (n = 8) or muscimol (n = 9) injections both increased the time spent exploring the displaced object while decreasing the time spent exploring the non-displaced object during the test session. *P = 0.05.

Figure 3.

Post-training dorsal hippocampal inactivation enhances long-term object recognition memory. Mice were habituated to the empty arena 1 d prior to training. During the 24-h test, the muscimol-treated group (n = 10) exhibited significantly higher preference for the novel object compared to animals treated with saline (n = 10) when tested 24 h after training. *P = 0.05.

Figure 4.

Time course of contextual habituation. Mice (n = 5) received daily exposures (5 min a day) to the empty experimental arena. The exploratory activity significantly decreased during the first 3 d. From day 3, mice showed constant exploratory behavior. *P = 0.05.

Figure 5.

Hippocampal inactivation has no effect on novel object recognition memory when training occurs in a familiar environment. Mice were habituated to the empty arena for 5 d prior to training. During the testing session, the muscimol-treated group (n = 6) exhibited a similar preference for the novel object compared with animals treated with saline (n = 10) when tested 24 h after training.