localization and function of glutamate receptor GluD2 in the retrosplenial granular cortex

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Hokkaido University
• Principal Investigator: Konno Kotaro 北海道大学, 医学研究院, 助教 (20599641)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: グルタミン酸受容体

Outline of Final Research Achievements

Little is known to date as to synaptic expression and function of glutamate receptor GluD2 outside the cerebellum. To address this issue, we examined the retrosplenial granular cortex (RSG), a cortical area that is involved in spatial memory and enriched with GluD2. By light and electron microscopy, GluD2 was concentrated at asymmetrical synapses in RSG neurons. Using anterograde and retrograde tracers, we addressed that afferents contacting GluD2-expressing synapses originated from the anteroventral thalamic nucleus (AV). Intriguingly, most RSG-targeting AV neurons expressed mRNA for Cbln1, a ligand for GluD1. Indeed, Cbln1 was clustered on RSG neurons and tightly apposed to GluD2 clusters. The density of AV afferents terminating on RSG neurons was significantly reduced in both GluD2-KO and Cbln1-KO mice. These results provide the molecular-anatomical evidence that GluD2 and Cbln1 interact to promote the formation of specific wiring between the AV and RSG.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

近年、GluD2の欠失変異をもつ家系が相次いで報告され、これらの患者において発語障害や精神遅滞などの高次脳機能障害といった予想外の症状が認められた。高次脳機能障害は小脳外の脳部位に発現しているGluD2の機能を反映している可能性が考えられるが、過去に小脳外におけるGluD2の局在や機能を示す報告はない。今回の成果はGluD2とCbln1が小脳外においても特定の神経回路基盤構築に重要な役割を担うことを示唆する。