Your browser doesn't support javascript.
loading
Calcium-permeable AMPA receptors govern PV neuron feature selectivity.
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.
Afiliación
  • Hong I; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ingiehong@jhmi.edu.
  • Kim J; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA. ingiehong@jhmi.edu.
  • Hainmueller T; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kim DW; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Keijser J; Emotion, Cognition and Behavior Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.
  • Johnson RC; Institute for Physiology I, University of Freiburg, Medical Faculty, Freiburg, Germany.
  • Park SH; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
  • Limjunyawong N; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Yang Z; Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, Denmark.
  • Cheon D; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Hwang T; Modelling of Cognitive Processes, Technical University of Berlin, Berlin, Germany.
  • Agarwal A; Charité-Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, Berlin, Germany.
  • Cholvin T; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Krienen FM; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA.
  • McCarroll SA; Section on Cognitive Neurophysiology and Imaging, National Institute of Mental Health, Bethesda, MD, USA.
  • Dong X; Department of Brain and Cognitive Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
  • Leopold DA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Blackshaw S; Center of Research Excellence in Allergy and Immunology, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Sprekeler H; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Bergles DE; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA.
  • Bartos M; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Brown SP; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA.
  • Huganir RL; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nature ; 2024 Oct 02.
Article en En | MEDLINE | ID: mdl-39358515
ABSTRACT
The brain helps us survive by forming internal representations of the external world1,2. Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4. 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 (α-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.
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos