2-B-P-013 〇大西 泰地¹、坂本 寛和¹、大久保 洋平²、並木 繁行¹、廣瀬 謙造¹ Onishi Taichi¹, Hirokazu Sakamoto¹, Yohei Okubo², Shigeyuki Namiki¹, Kenzo Hirose^{1 1}東京大・院医・細胞分子薬理学、²順天堂大・医・細胞分子薬理学 ¹Dept. Pharmacol., Grad. Sch. Med., Univ. of Tokyo, ²Dept. Pharmacol., Sch. Med., Juntendo Univ. 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.