Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice
© 2021. The Author(s)..
NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2-/- mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2-/- Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2-/- Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2-/- mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Nature communications - 12(2021), 1 vom: 25. Aug., Seite 5116 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Eunee [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 24.09.2021 Date Revised 24.09.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-021-25356-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329769731 |
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| 100 | 1 | |a Lee, Eunee |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Revised 24.09.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2-/- mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2-/- Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2-/- Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2-/- mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 650 | 7 | |a Parvalbumins |2 NLM | |
| 650 | 7 | |a Receptors, N-Methyl-D-Aspartate |2 NLM | |
| 650 | 7 | |a Shank2 protein, mouse |2 NLM | |
| 700 | 1 | |a Lee, Seungjoon |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Jae Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Woochul |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Changuk |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Suho |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jihye |e verfasserin |4 aut | |
| 700 | 1 | |a Ha, Seungmin |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Ryunhee |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, Taesun |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, Ye-Eun |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jisoo |e verfasserin |4 aut | |
| 700 | 1 | |a Noh, Young Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Rhim, Issac |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Soo Yeon |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Woohyun |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Taekyung |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Hyogeun |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Il-Joo |e verfasserin |4 aut | |
| 700 | 1 | |a Deisseroth, Karl |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sang Jeong |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Joo Min |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Min Whan |e verfasserin |4 aut | |
| 700 | 1 | |a Paik, Se-Bum |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Eunjoon |e verfasserin |4 aut | |
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