Hippocampal c-Fos activation in normal and LPA1-null mice after two object recognition tasks with different memory demands

Normal and LPA1-null mice, that have well reported hippocampal deficits, were assessed in an episodic-like what-when-where memory task or in a comparable task designed to test memory for familiar objects and locations by discriminating them from novels. Both genotypes performed the novelty recognition task but failed to learn the what-when-where task. However, normal mice showed what-when memory that was impaired in nulls. Each task elicited a different pattern of c-Fos expression. In normal mice, the what-when-where task induced more hippocampal c-Fos activation in the CA1 area than the novelty-based task, correlating with the what-when memory. LPA1-null mice displayed a basal c-Fos hyperactivity in the hippocampus and in the medial prefrontal cortex, which was regulated differently by the two behavioural tasks employed. Both tasks were matched in exploratory behaviour and c-Fos activation in stress-related brain areas for both genotypes. This study shows that the what-when-where memory task differs from a comparable novelty-based task in both the learning demands and the neuronal correlates. Moreover, results also stress the role of the LPA1 receptor in hippocampal functioning.

► We tested normal and LPA1-null mice in a what-where-when (W) or in a novelty (N) task.
► Both genotypes performed object and location memories in the N task.
► In the W task, normal mice showed ‘when’ memory and more CA1 c-Fos than in the N task.
► Null mice were impaired in the W task and showed altered hippocampal c-Fos expression.
► The W task involved distinct learning than the N task and more hippocampal demands.