Seeing through the brain mechanism for memory using transgenic mice
(Maki K. Yamada, Kazuya Kuboyama)

Kuboyama K, Inoue T, Hashimotodani Y, Itoh T, Suzuki T, Tetsuzawa A, Ohtsuka Y, Kinoshita R., Takara R, Miyazawa T, Gusain P, Kano M, Yamada MK.
Traceable stimulus-dependent rapid molecular changes in dendritic spines in the brain
Scientific Reports 10 15266 (2020)
DOI : 10.1038/s41598-020-72248-4
Maki K. Yamada seeks for one of the forms of plasticity “molecular plasticity”, represented by a change in the molecular distribution in spines. In a newly produced transgenic mouse line, AiCE-Tg, in which EGFP-CapZ is expressed, NMDA dependent relative intensification of EGFP-CapZ signals could be seen in a subset of spines ~20 minutes after unilateral visual or somatosensory stimulation.


We showed that an F-actin capping (stabilizing) protein CapZ accumulated and stayed in the spines, (postsynaptic varicosities) that given stimulus for long-term potentiation (LTP) (Genes to Cells 2010), thus the place for memory-related enhancement in neuronal synapses is expected to be labeled by EGFP-CapZ even in-vivo. On the other hand, we published another paper (Cerebral Cortex 2009) suggesting that memory-coding neurons would be included in a part of Arc-expressing neurons.  Thus, I made a transgenic mouse line having EGFP-CapZ driven by the Arc-promotor, to mark the candidate memory coding synapses and neurons. In the resulting mouse having blight fluorescence and normal learning ability, the EGFP-fluorescence is mainly found in a part of spines (, synaptic structure).

Abstract of most recent paper  

Dendritic spines function as microcompartments that can modify the efficiency of their associated synapses. Here, we analyzed stimulus-dependent molecular changes in spines. The F-actin capping protein CapZ accumulates in parts of dendritic spines within regions where long-term potentiation (LTP) has been induced. We produced a transgenic mouse line, AiCE-Tg, in which CapZ tagged with enhanced green fluorescence protein (EGFP-CapZ) is expressed. Twenty minutes after unilateral visual or somatosensory stimulation in AiCE-Tg mice, relative EGFP-CapZ signal intensification was seen in a subset of dendritic spines selectively in stimulated-side cortices; this right-left difference was abolished by NMDA receptor blockade. Immunolabeling of α-actinin, a PSD-95 binding protein that can recruit AMPA receptors, showed that the α-actinin signals colocalized more frequently in spines with the brightest EGFP-CapZ signals (top 100) than in spines with more typical EGFP-CapZ signal strength (top 1000). This stimulus-dependent in vivo redistribution of EGFP-CapZ represents a novel molecular event with plasticity-like characteristics, and bright EGFP-CapZ in AiCE-Tg mice make high-CapZ spines traceable in vivo and ex vivo. This mouse line has the potential to be used to reveal sequential molecular events, including synaptic tagging, and to relate multiple types of plasticity in these spines, extending knowledge related to memory mechanisms.

Future plans

Seeing through the brain mechanism for memory by multidisciplinary approach. If you are interested in collaborating with us, do not hesitate to contact us.


AiCE-Tg mice are available at BRC (or JAX, pending). Yamada can send you fixed brain samples (or live mice: SPF grade) upon requests. E-mail makiky-tky[at]

Ref from Yamada’s group

1. Cereb Cortex 19: 2572–2578, 2009
2. Genes Cells 15: 737-747, 2010

3.Scientific Reports, 10: 15266, 2020 DOI:10.1038/s41598-020-72248-4