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Differential regulation of medium spiny and cholinergic neurons in the nucleus accumbens core by the insular and medial prefrontal cortices in the rat

  • Neuroscience
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Abstract

The nucleus accumbens (NAc) receives cortical projections principally from the insular cortex (IC) and medial prefrontal cortex (mPFC). Among NAc neurons, cholinergic interneurons (ChNs) regulate the activities of medium spiny neurons (MSNs), which make up ~ 95% of NAc neurons, by modulating their firing and synaptic properties. However, little is known about the synaptic mechanisms, including their cell-type-dependent corticoaccumbal projection properties and cholinergic effects on the NAc core. Here, we performed whole-cell patch-clamp recordings from NAc MSNs and ChNs in acute brain slice preparations obtained from rats that received an AAV5-hSyn-ChR2(H134R)-mCherry injection into the IC or mPFC. Light stimulation of IC or mPFC axons induced comparable phase-locked excitatory postsynaptic currents (EPSCs) in MSNs. On the other hand, ChNs showed consistent EPSCs evoked by light stimulation of mPFC axons, whereas light stimulation of IC axons evoked much smaller EPSCs, which often showed failure in ChNs. Light-evoked EPSCs were abolished by tetrodotoxin and were recovered by 4-aminopyridine, suggesting that corticoaccumbal projections monosynaptically induce EPSCs in MSNs and ChNs. Carbachol effectively suppressed the amplitude of EPSCs in MSNs and ChNs evoked by light stimulation of IC or mPFC axons and in ChNs evoked by stimulating mPFC axons. The carbachol-induced suppression was recovered by atropine or pirenzepine, while preapplication of gallamine, J104129, PD102807, or AF-DX384 did not block the carbachol-induced EPSC suppression. These results suggest that NAc MSNs and ChNs are differentially regulated by excitatory projections from the IC and mPFC and that these corticoaccumbal excitatory inputs are modulated by M1 receptor activation.

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Abbreviations

AAV:

Adeno-associated virus

ACSF:

Artificial cerebrospinal fluid

ChNs:

Cholinergic interneurons

ChR2:

Channelrhodopsin-2

DNQX:

6,7-Dinitroquinoxaline-2,3-dione

EPSCs:

Excitatory postsynaptic currents

FSNs:

Fast-spiking neurons

IC:

Insular cortex

mPFC:

Medial prefrontal cortex

MSNs:

Medium spiny neurons

NAc:

Nucleus accumbens

TTX:

Tetrodotoxin

VGAT:

Vesicular GABA transporter

4-AP:

4-Aminopyridine

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Acknowledgements

VGAT-Venus transgenic rats were generated by Drs. Y. Yanagawa, M. Hirabayashi, and Y. Kawaguchi at the National Institute for Physiological Sciences, Okazaki, Japan, using pCS2-Venus provided by Dr. A. Miyawaki. We thank Prof. S. Fujita for the statistical analysis.

Funding

This work was supported by KAKENHI grant nos. 18K17019 and 21K16938 to Y.N., grant no. 17K11653 to K.Y., and grant no. 19H03821 to M.K. from the MEXT, Japan; grants from the Sato and Uemura foundations and Dental Research Center at Nihon University School of Dentistry also supported this work.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan

    Kensuke Hirose, Yuka Nakaya, Kohei Kitano, Kiyofumi Yamamoto & Masayuki Kobayashi

  2. Department of Pedodontics, Nihon University School of Dentistry, Tokyo, Japan

    Kensuke Hirose & Tetsuo Shirakawa

  3. Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan

    Yuka Nakaya, Kiyofumi Yamamoto, Tetsuo Shirakawa & Masayuki Kobayashi

  4. Department of Neurophysiology, Nara Medical University, 840 Shijo-cho, kashihara, Nara, 634-8521, Japan

    Yasuhiko Saito

  5. KOKORO-Biology Group, Laboratories for Integrated Biology, Osaka University Graduate School of Frontier Biosciences, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Ryosuke Kaneko

  6. Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Gunma, 371‑8511, Japan

    Yuchio Yanagawa

  7. Molecular Dynamics Imaging Unit, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Masayuki Kobayashi

Authors
  1. Kensuke Hirose
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  2. Yuka Nakaya
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  3. Kohei Kitano
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  4. Yasuhiko Saito
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  6. Yuchio Yanagawa
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  7. Kiyofumi Yamamoto
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  8. Tetsuo Shirakawa
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  9. Masayuki Kobayashi
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Contributions

Yuka Nakaya, Kiyofumi Yamamoto, and Masayuki Kobayashi conceived and designed the research. Kensuke Hirose, Yuka Nakaya, Kohei Kitano, and Kiyofumi Yamamoto conducted experiments. Yasuhiko Saito, Ryosuke Kaneko, and Yuchio Yanagawa developed the choline acetyltransferase (ChAT)-tdTomato transgenic rat. Data analyses were performed by Kensuke Hirose, Yuka Nakaya, Kohei Kitano, Kiyofumi Yamamoto, and Masayuki Kobayashi. The draft of the manuscript was written by Kensuke Hirose, Yuka Nakaya, and Kiyofumi Yamamoto, Tetsuo Shirakawa, and Masayuki Kobayashi. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masayuki Kobayashi.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution where the experiments were performed. All experiments were approved by the Animal Experimentation Committee at Nihon University and were carried out according to the National Institute of Health Guide for the Care and Use of Laboratory Animals.

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The authors declare no competing interests.

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Hirose, K., Nakaya, Y., Kitano, K. et al. Differential regulation of medium spiny and cholinergic neurons in the nucleus accumbens core by the insular and medial prefrontal cortices in the rat. Pflugers Arch - Eur J Physiol 473, 1911–1924 (2021). https://doi.org/10.1007/s00424-021-02634-y

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