Neur1 and Neur2 are required for hippocampus-dependent spatial memory and synaptic plasticity.

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.

Synaptic Engram.

The concept of the engram refers to structural and/or physiological changes that underlie memory associations during learning. However, the precise biological basis of the engram remains elusive, with ongoing controversy regarding whether it resides at the cellular level or within the synaptic connections between activated cells. Here, we briefly review the studies investigating the cellular engram and the challenges they encounter. Subsequently, we delve into the biological basis of the engram within synaptic connections. In this regard, we introduce the history of synaptic engrams and discuss recent findings suggesting that synaptic plasticity serves as a substrate for memory. Additionally, we provide an overview of key technologies utilized in the study of synaptic plasticity.

Hippocampal engram networks for fear memory recruit new synapses and modify pre-existing synapses in vivo.

As basic units of neural networks, ensembles of synapses underlie cognitive functions such as learning and memory. These synaptic engrams show elevated synaptic density among engram cells following contextual fear memory formation. Subsequent analysis of the CA3-CA1 engram synapse revealed larger spine sizes, as the synaptic connectivity correlated with the memory strength. Here, we elucidate the synapse dynamics between CA3 and CA1 by tracking identical synapses at multiple time points by adapting two-photon microscopy and dual-eGRASP technique in vivo. After memory formation, synaptic connections between engram populations are enhanced in conjunction with synaptogenesis within the hippocampal network. However, extinction learning specifically correlated with the disappearance of CA3 engram to CA1 engram (E-E) synapses. We observed "newly formed" synapses near pre-existing synapses, which clustered CA3-CA1 engram synapses after fear memory formation. Overall, we conclude that dynamics at CA3 to CA1 E-E synapses are key sites for modification during fear memory states.

The Primary Motor Cortex: The Hub of Motor Learning in Rodents.

The primary motor cortex, a dynamic center for overall motion control and decision making, undergoes significant alterations upon neural stimulation. Over the last few decades, data from numerous studies using rodent models have improved our understanding of the morphological and functional plasticity of the primary motor cortex. In particular, spatially specific formation of dendritic spines and their maintenance during distinct behaviors is considered crucial for motor learning. However, whether the modifications of specific synapses are associated with motor learning should be studied further. In this review, we summarized the findings of prior studies on the features and dynamics of the primary motor cortex in rodents.