The firing of theta state-related septal cholinergic neurons disrupt hippocampal ripple oscillations via muscarinic receptors

Xiaoyu Ma; Yiyao Zhang; Lina Wang; Na Li; Edi Barkai; Xiaohui Zhang; Longnian Lin; Jiamin Xu

doi:10.1523/JNEUROSCI.1568-19.2020

The firing of theta state-related septal cholinergic neurons disrupt hippocampal ripple oscillations via muscarinic receptors

Xiaoyu Ma, Yiyao Zhang, Lina Wang, Na Li, Edi Barkai, Xiaohui Zhang, Longnian Lin, Jiamin Xu

Department of Neurobiology

Research output: Contribution to journal › Article › peer-review

Abstract

The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M₂ or M₄ receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

Original language	English
Pages (from-to)	3591-3603
Number of pages	13
Journal	Journal of Neuroscience
Volume	40
Issue number	18
DOIs	https://doi.org/10.1523/JNEUROSCI.1568-19.2020
State	Published - 29 Apr 2020

Bibliographical note

Funding Information:
Received Aug. 5, 2019; revised Mar. 11, 2020; accepted Mar. 13, 2020. Author contributions: X.M., L.L., and J.X. designed research; X.M., Y.Z., L.W. and N.L. performed research; X.M., Y.Z., X.Z., L.L., and J.X. analyzed data; and X.M., Y.Z., E.B., L.L., and J.X. wrote the paper. *X.M. and Y.Z. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (Grant 31661143038 and 31800890), Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX05), Shanghai Sailing program (17YF1426800), Shanghai Tongji University Education Development Foundation (to L.L.) and the the Israel Science Foundation (2523/16). We thank Dr. Guoping Feng (Massachusetts Institute of Technology) for generously sharing the ChATChR2-EYFP mouse line. The authors declare no competing financial interests. Correspondence should be addressed to Longnian Lin at lnlin@brain.ecnu.edu.cn or Jiamin Xu at xujiamin@ bio.ecnu.edu.cn. https://doi.org/10.1523/JNEUROSCI.1568-19.2020 Copyright © 2020 the authors

Publisher Copyright:
Copyright © 2020 the authors

Keywords

Acetylcholine
Hippocampus
Medial septum
Muscarinic receptors
Sharp wave-ripple
Optogenetics/methods
Muscarinic Antagonists/pharmacology
Theta Rhythm/drug effects
Action Potentials/drug effects
Hippocampus/chemistry
Male
Mice, Transgenic
Cholinergic Neurons/chemistry
Cholinergic Agonists/pharmacology
Receptor, Muscarinic M2/agonists
Animals
Receptors, Muscarinic/physiology
Mice
Receptor, Muscarinic M4/agonists
Organ Culture Techniques

ASJC Scopus subject areas

Medicine (all)

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10.1523/JNEUROSCI.1568-19.2020

Cite this

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title = "The firing of theta state-related septal cholinergic neurons disrupt hippocampal ripple oscillations via muscarinic receptors",

abstract = "The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.",

keywords = "Acetylcholine, Hippocampus, Medial septum, Muscarinic receptors, Sharp wave-ripple, Optogenetics/methods, Muscarinic Antagonists/pharmacology, Theta Rhythm/drug effects, Action Potentials/drug effects, Hippocampus/chemistry, Male, Mice, Transgenic, Cholinergic Neurons/chemistry, Cholinergic Agonists/pharmacology, Receptor, Muscarinic M2/agonists, Animals, Receptors, Muscarinic/physiology, Mice, Receptor, Muscarinic M4/agonists, Organ Culture Techniques",

author = "Xiaoyu Ma and Yiyao Zhang and Lina Wang and Na Li and Edi Barkai and Xiaohui Zhang and Longnian Lin and Jiamin Xu",

note = "Funding Information: Received Aug. 5, 2019; revised Mar. 11, 2020; accepted Mar. 13, 2020. Author contributions: X.M., L.L., and J.X. designed research; X.M., Y.Z., L.W. and N.L. performed research; X.M., Y.Z., X.Z., L.L., and J.X. analyzed data; and X.M., Y.Z., E.B., L.L., and J.X. wrote the paper. *X.M. and Y.Z. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (Grant 31661143038 and 31800890), Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX05), Shanghai Sailing program (17YF1426800), Shanghai Tongji University Education Development Foundation (to L.L.) and the the Israel Science Foundation (2523/16). We thank Dr. Guoping Feng (Massachusetts Institute of Technology) for generously sharing the ChATChR2-EYFP mouse line. The authors declare no competing financial interests. Correspondence should be addressed to Longnian Lin at lnlin@brain.ecnu.edu.cn or Jiamin Xu at xujiamin@ bio.ecnu.edu.cn. https://doi.org/10.1523/JNEUROSCI.1568-19.2020 Copyright {\textcopyright} 2020 the authors Publisher Copyright: Copyright {\textcopyright} 2020 the authors",

year = "2020",

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day = "29",

doi = "10.1523/JNEUROSCI.1568-19.2020",

language = "English",

volume = "40",

pages = "3591--3603",

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T1 - The firing of theta state-related septal cholinergic neurons disrupt hippocampal ripple oscillations via muscarinic receptors

AU - Ma, Xiaoyu

AU - Zhang, Yiyao

AU - Wang, Lina

AU - Li, Na

AU - Barkai, Edi

AU - Zhang, Xiaohui

AU - Lin, Longnian

AU - Xu, Jiamin

N1 - Funding Information: Received Aug. 5, 2019; revised Mar. 11, 2020; accepted Mar. 13, 2020. Author contributions: X.M., L.L., and J.X. designed research; X.M., Y.Z., L.W. and N.L. performed research; X.M., Y.Z., X.Z., L.L., and J.X. analyzed data; and X.M., Y.Z., E.B., L.L., and J.X. wrote the paper. *X.M. and Y.Z. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (Grant 31661143038 and 31800890), Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX05), Shanghai Sailing program (17YF1426800), Shanghai Tongji University Education Development Foundation (to L.L.) and the the Israel Science Foundation (2523/16). We thank Dr. Guoping Feng (Massachusetts Institute of Technology) for generously sharing the ChATChR2-EYFP mouse line. The authors declare no competing financial interests. Correspondence should be addressed to Longnian Lin at lnlin@brain.ecnu.edu.cn or Jiamin Xu at xujiamin@ bio.ecnu.edu.cn. https://doi.org/10.1523/JNEUROSCI.1568-19.2020 Copyright © 2020 the authors Publisher Copyright: Copyright © 2020 the authors

PY - 2020/4/29

Y1 - 2020/4/29

N2 - The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

AB - The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate.

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KW - Hippocampus

KW - Medial septum

KW - Muscarinic receptors

KW - Sharp wave-ripple

KW - Optogenetics/methods

KW - Muscarinic Antagonists/pharmacology

KW - Theta Rhythm/drug effects

KW - Action Potentials/drug effects

KW - Hippocampus/chemistry

KW - Male

KW - Mice, Transgenic

KW - Cholinergic Neurons/chemistry

KW - Cholinergic Agonists/pharmacology

KW - Receptor, Muscarinic M2/agonists

KW - Animals

KW - Receptors, Muscarinic/physiology

KW - Mice

KW - Receptor, Muscarinic M4/agonists

KW - Organ Culture Techniques

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DO - 10.1523/JNEUROSCI.1568-19.2020

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SN - 0270-6474

VL - 40

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JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 18

ER -

The firing of theta state-related septal cholinergic neurons disrupt hippocampal ripple oscillations via muscarinic receptors

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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