Btbd11 supports cell-type-specific synaptic function

Alexei M. Bygrave; Ayesha Sengupta; Ella P. Jackert; Mehroz Ahmed; Beloved Adenuga; Erik Nelson; Hana L. Goldschmidt; Richard C. Johnson; Haining Zhong; Felix L. Yeh; Morgan Sheng; Richard L. Huganir

Cell Reports (Jun 2023)

Btbd11 supports cell-type-specific synaptic function

Alexei M. Bygrave,
Ayesha Sengupta,
Ella P. Jackert,
Mehroz Ahmed,
Beloved Adenuga,
Erik Nelson,
Hana L. Goldschmidt,
Richard C. Johnson,
Haining Zhong,
Felix L. Yeh,
Morgan Sheng,
Richard L. Huganir

Affiliations

Alexei M. Bygrave: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
Ayesha Sengupta: National Institute on Drug Abuse, Bayview Boulevard, Baltimore, MD 21224, USA
Ella P. Jackert: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mehroz Ahmed: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Beloved Adenuga: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Erik Nelson: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hana L. Goldschmidt: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Richard C. Johnson: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Haining Zhong: Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA
Felix L. Yeh: Department of Neuroscience, Genentech, Inc, South San Francisco, CA 94080, USA
Morgan Sheng: Department of Neuroscience, Genentech, Inc, South San Francisco, CA 94080, USA
Richard L. Huganir: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 6
p. 112591

Abstract

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Summary: Synapses in the brain exhibit cell-type-specific differences in basal synaptic transmission and plasticity. Here, we evaluated cell-type-specific specializations in the composition of glutamatergic synapses, identifying Btbd11 as an inhibitory interneuron-specific, synapse-enriched protein. Btbd11 is highly conserved across species and binds to core postsynaptic proteins, including Psd-95. Intriguingly, we show that Btbd11 can undergo liquid-liquid phase separation when expressed with Psd-95, supporting the idea that the glutamatergic postsynaptic density in synapses in inhibitory interneurons exists in a phase-separated state. Knockout of Btbd11 decreased glutamatergic signaling onto parvalbumin-positive interneurons. Further, both in vitro and in vivo, Btbd11 knockout disrupts network activity. At the behavioral level, Btbd11 knockout from interneurons alters exploratory behavior, measures of anxiety, and sensitizes mice to pharmacologically induced hyperactivity following NMDA receptor antagonist challenge. Our findings identify a cell-type-specific mechanism that supports glutamatergic synapse function in inhibitory interneurons—with implications for circuit function and animal behavior.

CP: Neuroscience

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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