Calcium-permeable AMPA receptors govern PV neuron feature selectivity

Ingie Hong (), Juhyun Kim, Thomas Hainmueller, Dong Won Kim, Joram Keijser, Richard C. Johnson, Soo Hyun Park, Nathachit Limjunyawong, Zhuonan Yang, David Cheon, Taeyoung Hwang, Amit Agarwal, Thibault Cholvin, Fenna M. Krienen, Steven A. McCarroll, Xinzhong Dong, David A. Leopold, Seth Blackshaw, Henning Sprekeler, Dwight E. Bergles, Marlene Bartos, Solange P. Brown and Richard L. Huganir ()
Additional contact information
Ingie Hong: Johns Hopkins University School of Medicine
Juhyun Kim: Johns Hopkins University School of Medicine
Thomas Hainmueller: Medical Faculty
Dong Won Kim: Johns Hopkins University School of Medicine
Joram Keijser: Technical University of Berlin
Richard C. Johnson: Johns Hopkins University School of Medicine
Soo Hyun Park: National Institute of Mental Health
Nathachit Limjunyawong: Johns Hopkins University School of Medicine
Zhuonan Yang: Johns Hopkins University School of Medicine
David Cheon: Johns Hopkins University School of Medicine
Taeyoung Hwang: Johns Hopkins University School of Medicine
Amit Agarwal: Johns Hopkins University School of Medicine
Thibault Cholvin: Medical Faculty
Fenna M. Krienen: Princeton University
Steven A. McCarroll: Harvard Medical School
Xinzhong Dong: Johns Hopkins University School of Medicine
David A. Leopold: National Institute of Mental Health
Seth Blackshaw: Johns Hopkins University School of Medicine
Henning Sprekeler: Technical University of Berlin
Dwight E. Bergles: Johns Hopkins University School of Medicine
Marlene Bartos: Medical Faculty
Solange P. Brown: Johns Hopkins University School of Medicine
Richard L. Huganir: Johns Hopkins University School of Medicine

Nature, 2024, vol. 635, issue 8038, 398-405

Abstract: 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.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-08027-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:635:y:2024:i:8038:d:10.1038_s41586-024-08027-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-08027-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().