Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory.

Nr4a1 and Nr4a2 are transcription factors and immediate early genes belonging to the nuclear receptor Nr4a family. In this study, we examine their role in long-term memory formation for object location and object recognition. Using siRNA to block expression of either Nr4a1 or Nr4a2, we found that Nr4a2 is necessary for both long-term memory for object location and object recognition. In contrast, Nr4a1 appears to be necessary only for object location. Indeed, their roles in these different types of long-term memory may be dependent on their expression in the brain, as NR4A2 was found to be expressed in hippocampal neurons (associated with object location memory) as well as in the insular and perirhinal cortex (associated with object recognition memory), whereas NR4A1 showed minimal neuronal expression in these cortical areas. These results begin to elucidate how NR4A1 and NR4A2 differentially contribute to object location versus object recognition memory.

Temporal dynamics of Arc gene induction in hippocampus: relationship to context memory formation.

Past studies have proposed a role for the hippocampus in the rapid encoding of context memories. Despite this, there is little data regarding the molecular processes underlying the stable formation of a context representation that occurs in the time window established through such behavioral studies. One task that is useful for investigating the rapid encoding of context is contextual fear conditioning (CFC). Behavioral studies demonstrate that animals require approximately 30 s of exploration prior to a footshock to form a contextual representation supporting CFC. Thus, any potential molecular process required for the stabilization of the cellular representation for context must be activated within this narrow and behaviorally defined time window. Detection of the immediate-early gene Arc presents an ideal method to assess the activation of specific neuronal ensembles, given past studies showing the context specific expression of Arc in CA3 and CA1 subfields and the role of Arc in hippocampal long-term synaptic plasticity. Therefore, we examined the temporal dynamics of Arc induction within the hippocampus after brief context exposure to determine whether experience-dependent Arc expression could be involved in the rapid encoding of incidental context memories. We found that the duration of context exposure differentially activated Arc expression in hippocampal subfields, with CA3 showing rapid engagement within as little as 3 s of exposure. By contrast, Arc induction in CA1 required 30 s of context exposure to reach maximal levels. A parallel behavioral experiment revealed that 30 s, but not 3 s, exposure to a context resulted in strong conditioned freezing 24 h later, consistent with past studies from other laboratories. The current study is the first to examine the rapid temporal dynamics of Arc induction in hippocampus in a well-defined context memory paradigm. These studies demonstrate within 30 s of context exposure Arc is fully activated in CA3 and CA1, suggesting that the engagement of plastic processes requiring Arc function (such as long-term potentiation) occurs within the same temporal domain as that required for behavioral conditioning.