遺伝子改変マウスを用いた記憶・学習の動作原理の解明
キーワード：記憶・学習,マウス
2019.07.

主要原著論文

1.	Kyogo S Kobayashi , Naoki Matsuo , Persistent representation of the environment in the hippocampus, Cell Reports, 10.1016/j.celrep.2022.111989, 2023.01, In the hippocampus, environmental changes elicit rearrangement of active neuronal ensembles or remapping of place cells. However, it remains elusive how the brain ensures a consistent representation of a certain environment itself despite salient events occurring there. Here, we longitudinally tracked calcium dynamics of dorsal hippocampal CA1 neurons in mice subjected to contextual fear conditioning and extinction training. Overall population activities were significantly changed by fear conditioning and were responsive to footshocks and freezing. However, a small subset of neurons, termed environment cells, were consistently active in a specific environment irrespective of experiences. A decoder modeling study showed that these cells, but not place cells, were able to predict the environment to which the mouse was exposed. Environment cells might underlie the constancy of cognition for distinct environments across time and events. Additionally, our study highlights the functional heterogeneity of cells in the hippocampus..
2.	Leon G. Reijmers, Brian L. Perkins, Naoki Matsuo, Mark Mayford, Localization of a stable neural correlate of associative memory, Science, 10.1126/science.1143839, 317, 5842, 1230-1233, 2007.08, [URL], Do learning and retrieval of a memory activate the same neurons? Does the number of reactivated neurons correlate with memory strength? We developed a transgenic mouse that enables the long-lasting genetic tagging of c-fos-active neurons. We found neurons in the basolateral amygdala that are activated during Pavlovian fear conditioning and are reactivated during memory retrieval. The number of reactivated neurons correlated positively with the behavioral expression of the fear memory, indicating a stable neural correlate of associative memory. The ability to manipulate these neurons genetically should allow a more precise dissection of the molecular mechanisms of memory encoding within a distributed neuronal network..
3.	Naoki Matsuo, Leon Reijmers, Mark Mayford, Spine-type-specific recruitment of newly synthesized AMPA receptors with learning, Science, 10.1126/science.1149967, 319, 5866, 1104-1107, 2008.02, [URL], The stabilization of long-term memories requires de novo protein synthesis. How can proteins, synthesized in the soma, act on specific synapses that participate in a given memory? We studied the dynamics of newly synthesized AMPA-type glutamate receptors (AMPARs) induced with learning using transgenic mice expressing the GluR1 subunit fused to green fluorescent protein (GFP-GluR1) under control of the c-fos promoter. We found learning-associated recruitment of newly synthesized GFP-GluR1 selectively to mushroom-type spines in adult hippocampal CA1 neurons 24 hours after fear conditioning. Our results are consistent with a "synaptic tagging" model to allow activated synapses to subsequently capture newly synthesized receptor and also demonstrate a critical functional distinction in the mushroom spines with learning..
4.	Naoki Matsuo, Irreplaceability of neuronal ensembles after memory allocation, Cell Reports, 10.1016/j.celrep.2015.03.042, 11, 3, 351-357, 2015.04, [URL], Lesion studies suggest that an alternative system can compensate for damage to the primary region employed when animals acquire a memory. However, it is unclear whether functional compensation occurs at the cellular ensemble level. Here, we inhibited the activities of a specific subset of neurons activated during initial learning by utilizing a transgenic mouse that expresses tetanus toxin (TeNT) under the control of the c-fos promoter. Notably, suppression interfered with relearning while sparing the ability to acquire and express fear memory for a distinct context. These results suggest that the activity of the initial ensemble is preferentially dedicated to the same learning and that it is not replaceable once it is allocated. Our results provide substantial insights into the machinery underlying how the brain allocates individual memories todiscrete neuronal ensembles and how it ensures that repetitive learning strengthens memory by reactivating the same neuronal ensembles..

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海外渡航状況, 海外での教育研究歴