Calcium-permeable AMPA receptors govern PV neuron feature selectivity
成果类型：
Article
署名作者：
Hong, Ingie; Kim, Juhyun; Hainmueller, Thomas; Kim, Dong Won; Keijser, Joram; Johnson, Richard C.; Park, Soo Hyun; Limjunyawong, Nathachit; Yang, Zhuonan; Cheon, David; Hwang, Taeyoung; Agarwal, Amit; Cholvin, Thibault; Krienen, Fenna M.; McCarroll, Steven A.; Dong, Xinzhong; Leopold, David A.; Blackshaw, Seth; Sprekeler, Henning; Bergles, Dwight E.; Bartos, Marlene; Brown, Solange P.; Huganir, Richard L.
署名单位：
Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Korea Brain Research Institute (KBRI); University of Freiburg; Technical University of Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); Korea Advanced Institute of Science & Technology (KAIST); Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Ruprecht Karls University Heidelberg; Princeton University; Harvard University; Harvard Medical School; Johns Hopkins University; Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins University; NYU Langone Medical Center; New York University; Aarhus University; Aarhus University; Mahidol University
刊物名称：
Nature
ISSN/ISSBN：
0028-6904
DOI：
10.1038/s41586-024-08027-2
发表日期：
2024-11-14
页码：
398-+
关键词：
inhibitory neurons
cell-types
direction selectivity
excitatory synapses
synaptic plasticity
subunit composition
ca2+ permeability
glua2 subunit
ion flow
interneurons
摘要：
The brain helps us survive by forming internal representations of the external world(1,2). Excitatory cortical neurons are often precisely tuned to specific external stimuli(3,4). However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5. PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs)(6,7). Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2 mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory-PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex.