Search

Neur1 and Neur2, mouse homologs of the Drosophila neur gene, consist of two neuralized homology repeat domains and a RING domain. Both Neur1 and Neur2 are expressed in the whole adult brain and encode E3 ubiquitin ligases, which play a crucial role in the Notch signaling pathways. A previous study reported that overexpression of Neur1 enhances hippocampus‐dependent memory, whereas the role of Neur2 remains largely unknown. Here, we aimed to elucidate the respective roles of Neur1 and Neur2 in hippocampus‐dependent memory using three lines of genetically modified mice: Neur1 knock‐out, Neur2 knock‐out, and Neur1 and Neur2 double knock‐out (D‐KO). Our results showed that spatial memory was impaired when both Neur1 and Neur2 were deleted, but not in the individual knock‐out of either Neur1 or Neur2. In addition, basal synaptic properties estimated by input–output relationships and paired‐pulse facilitation did not change, but a form of long‐term potentiation that requires protein synthesis was specifically impaired in the D‐KO mice. These results collectively suggest that Neur1 and Neur2 are crucially involved in hippocampus‐dependent spatial memory and synaptic plasticity. [ABSTRACT FROM AUTHOR]

• Transient elevation of cAMP during systems consolidation leads to increased miniature excitatory synaptic currents in the ACC. • Transient elevation of cAMP in the ACC during systems consolidation induces remote memory enhancement. • During systems consolidation, the ACC plays a key role in the cAMP-dependent regulation of remote memory. Memory is stored in our brains over a temporally graded transition. With time, recently formed memories are transformed into remote memories for permanent storage; multiple brain regions, such as the hippocampus and neocortex, participate in this process. In this study, we aimed to understand the molecular mechanism of systems consolidation of memory and to investigate the brain regions that contribute to this regulation. We first carried out a contextual fear memory test using a transgenic mouse line, which expressed exogenously-derived Aplysia octopamine receptors in the forebrain region, such that, in response to octopamine treatment, cyclic adenosine monophosphate (cAMP) levels could be transiently elevated. From this experiment, we revealed that transient elevation of cAMP levels in the forebrain during systems consolidation led to an enhancement in remote fear memory and increased miniature excitatory synaptic currents in layer II/III of the anterior cingulate cortex (ACC). Furthermore, using an adeno-associated-virus-driven DREADD system, we investigated the specific regions in the forebrain that contribute to the regulation of memory transfer into long-term associations. Our results implied that transient elevation of cAMP levels was induced chemogenetically in the ACC, but not in the hippocampus, and showed a significant enhancement of remote memory. This finding suggests that neuronal activation during systems consolidation through the elevation of cAMP levels in the ACC contributes to remote memory enhancement. [ABSTRACT FROM AUTHOR]