新規文脈探索後の海馬苔状線維終末におけるシナプス分子の活動依存的減少

• Published in: 日本薬理学会年会要旨集 p. 2-B-P-013
• Main Authors: 大久保, 洋平, 並木, 繁行, 廣瀬, 謙造, 大西, 泰地, 坂本, 寛和
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: dentate gyrus; hippocampus; presynaptic terminal; synapse
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_2-B-P-013

In the dentate gyrus (DG), the novel context (NC) exploration activates a sparse population of granule cells (GCs). Stimulated GCs reshape computations in the hippocampal neural circuitry by modifying their synaptic plasticity, particularly at mossy fiber terminals (MFTs). Nevertheless, it remains elusive what molecular changes occur at MFTs of GCs which are active during the NC exposure.In this study, we used an artificial, activity-dependent promoter called Robust Activity Marking (RAM) to label activated neurons. In the DG, we introduced AAV expressing V5 tag fused synaptophysin (V5-SYP) via RAM promoter to label MFTs of GCs that exhibited activity during the NC exploration. The number of V5-SYP positive MFTs was threefold higher in mice exposed to the NC compared to unexposed counterparts. Next, we quantified various presynaptic molecules in V5 positive and negative MFTs, one day subsequent to exposure to the NC. We found V5-SYP positive MFTs exhibited significantly diminished levels of active zone molecules such as Munc13-1, RIM1, and CAST. Conversely, the amount of Cav2.1 showed no difference between the two types of MFTs. These findings suggest that MFTs of activated GCs attenuate their synaptic transmission by downregulating key molecules that constitute the synaptic machinery of transmitter release.