The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex

Rachel Larsen; Alatheia Proue; Earl Parker Scott; Matthew Christiansen; Yasushi Nakagawa

doi:10.1523/ENEURO.0018-19.2019

The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex

Rachel Larsen, Alatheia Proue, Earl Parker Scott, Matthew Christiansen, Yasushi Nakagawa

Neuroscience

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

21 Scopus citations

Abstract

GABAergic inhibitory neurons in the prefrontal cortex (PFC) play crucial roles in higher cognitive functions. Despite the link between aberrant development of PFC interneurons and a number of psychiatric disorders, mechanisms underlying the development of these neurons are poorly understood. Here we show that the retinoic acid (RA)-degrading enzyme CYP26B1 (cytochrome P450 family 26, subfamily B, member 1) is transiently expressed in the mouse frontal cortex during postnatal development, and that medial ganglionic eminence (MGE)-derived interneurons, particularly in parvalbumin (PV)-expressing neurons, are the main cell type that has active RA signaling during this period. We found that frontal cortex-specific Cyp26b1 knock-out mice had an increased density of PV-expressing, but not somatostatin-expressing, interneurons in medial PFC, indicating a novel role of RA signaling in controlling PV neuron development. The initiation of Cyp26b1 expression in neonatal PFC coincides with the establishment of connections between the thalamus and the PFC. We found that these connections are required for the postnatal expression of Cyp26b1 in medial PFC. In addition to this regionspecific role in postnatal PFC that regulates RA signaling and PV neuron development, the thalamocortical connectivity had an earlier role in controlling radial dispersion of MGE-derived interneurons throughout embryonic neocortex. In summary, our results suggest that the thalamus plays multiple, temporally separate roles in interneuron development in the PFC.

Original language	English (US)
Article number	e0018-19.2019
Journal	eNeuro
Volume	6
Issue number	1
DOIs	https://doi.org/10.1523/ENEURO.0018-19.2019
State	Published - Jan 1 2019

Bibliographical note

Funding Information:
Received January 14, 2019; accepted February 11, 2019; First published February 25, 2019. The authors declare no competing financial interests. Author contributions: R.L., A.P., E.P.S., M.C., and Y.N. performed research; R.L., A.P., E.P.S., and Y.N. analyzed data; Y.N. designed research; Y.N. contributed unpublished reagents/analytic tools; Y.N. wrote the paper. This work was supported by grants to Y.N. from National Institutes of Health (R21-MH-105759), Brain and Behavior Research Foundation (Essel Investigator), Winston and Maxim Wallin Neuroscience Discovery Fund, and Academic Health Center of the University of Minnesota. *R.L., A.P., and E.P.S. contributed equally to the work. We thank Steven McLoon (University of Minnesota, Minneapolis, MN), Goi-chi Miyoshi (Tokyo Women’s Medical University, Tokyo, Japan), and Timothy Monko (University of Minnesota, Minneapolis, MN) for helpful comments and discussions; Thomas Bao, Samantha Dabruzzi, Shaylene McCue, Morgan McCullough, and Carmen Tso (University of Minnesota, Minneapolis, MN) for technical assistance; and the University of Minnesota Vision Core and Paulo Kofuji for allowing us to use their Olympus confocal microscope. Zachery Werkhoven and Melody Lee (University of Minnesota, Minneapolis, MN) contributed to the initial phase of the project. We also thank Martyn Goulding (Salt Institute, La Jolla, CA) for providing Rosa26stop-TeNT/stop-TeNT mice; Hiroshi Hamada (RIKEN Center for Biosystems Dynamics Research, Kobe, Japan) and Maria Morasso (National Institutes of Health, Bethesda, MD) for providing Cyp26b1flox/flox mice; Eric Turner (University of Washington, Seattle, WA) for providing Syt6Cre/+ mice; Rob Machold for providing Pvalb, Vip, and Sst cDNAs; and John Rubenstein for providing Lhx6 cDNA. Correspondence should be addressed to Yasushi Nakagawa at nakagawa@umn.edu. https://doi.org/10.1523/ENEURO.0018-19.2019 Copyright © 2019 Larsen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Funding Information:
This work was supported by grants to Y.N. from National Institutes of Health (R21-MH-105759), Brain and Behavior Research Foundation (Essel Investigator), Winston and Maxim Wallin Neuroscience Discovery Fund, and Academic Health Center of the University of Minnesota.

Publisher Copyright:
© 2019 Larsen et al.

Keywords

Cyp26b1
Interneurons
Parvalbumin
Prefrontal cortex
Retinoic acid
Thalamocortical

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385081

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title = "The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex",

abstract = "GABAergic inhibitory neurons in the prefrontal cortex (PFC) play crucial roles in higher cognitive functions. Despite the link between aberrant development of PFC interneurons and a number of psychiatric disorders, mechanisms underlying the development of these neurons are poorly understood. Here we show that the retinoic acid (RA)-degrading enzyme CYP26B1 (cytochrome P450 family 26, subfamily B, member 1) is transiently expressed in the mouse frontal cortex during postnatal development, and that medial ganglionic eminence (MGE)-derived interneurons, particularly in parvalbumin (PV)-expressing neurons, are the main cell type that has active RA signaling during this period. We found that frontal cortex-specific Cyp26b1 knock-out mice had an increased density of PV-expressing, but not somatostatin-expressing, interneurons in medial PFC, indicating a novel role of RA signaling in controlling PV neuron development. The initiation of Cyp26b1 expression in neonatal PFC coincides with the establishment of connections between the thalamus and the PFC. We found that these connections are required for the postnatal expression of Cyp26b1 in medial PFC. In addition to this regionspecific role in postnatal PFC that regulates RA signaling and PV neuron development, the thalamocortical connectivity had an earlier role in controlling radial dispersion of MGE-derived interneurons throughout embryonic neocortex. In summary, our results suggest that the thalamus plays multiple, temporally separate roles in interneuron development in the PFC.",

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note = "Funding Information: Received January 14, 2019; accepted February 11, 2019; First published February 25, 2019. The authors declare no competing financial interests. Author contributions: R.L., A.P., E.P.S., M.C., and Y.N. performed research; R.L., A.P., E.P.S., and Y.N. analyzed data; Y.N. designed research; Y.N. contributed unpublished reagents/analytic tools; Y.N. wrote the paper. This work was supported by grants to Y.N. from National Institutes of Health (R21-MH-105759), Brain and Behavior Research Foundation (Essel Investigator), Winston and Maxim Wallin Neuroscience Discovery Fund, and Academic Health Center of the University of Minnesota. *R.L., A.P., and E.P.S. contributed equally to the work. We thank Steven McLoon (University of Minnesota, Minneapolis, MN), Goi-chi Miyoshi (Tokyo Women{\textquoteright}s Medical University, Tokyo, Japan), and Timothy Monko (University of Minnesota, Minneapolis, MN) for helpful comments and discussions; Thomas Bao, Samantha Dabruzzi, Shaylene McCue, Morgan McCullough, and Carmen Tso (University of Minnesota, Minneapolis, MN) for technical assistance; and the University of Minnesota Vision Core and Paulo Kofuji for allowing us to use their Olympus confocal microscope. Zachery Werkhoven and Melody Lee (University of Minnesota, Minneapolis, MN) contributed to the initial phase of the project. We also thank Martyn Goulding (Salt Institute, La Jolla, CA) for providing Rosa26stop-TeNT/stop-TeNT mice; Hiroshi Hamada (RIKEN Center for Biosystems Dynamics Research, Kobe, Japan) and Maria Morasso (National Institutes of Health, Bethesda, MD) for providing Cyp26b1flox/flox mice; Eric Turner (University of Washington, Seattle, WA) for providing Syt6Cre/+ mice; Rob Machold for providing Pvalb, Vip, and Sst cDNAs; and John Rubenstein for providing Lhx6 cDNA. Correspondence should be addressed to Yasushi Nakagawa at nakagawa@umn.edu. https://doi.org/10.1523/ENEURO.0018-19.2019 Copyright {\textcopyright} 2019 Larsen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Funding Information: This work was supported by grants to Y.N. from National Institutes of Health (R21-MH-105759), Brain and Behavior Research Foundation (Essel Investigator), Winston and Maxim Wallin Neuroscience Discovery Fund, and Academic Health Center of the University of Minnesota. Publisher Copyright: {\textcopyright} 2019 Larsen et al.",

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N2 - GABAergic inhibitory neurons in the prefrontal cortex (PFC) play crucial roles in higher cognitive functions. Despite the link between aberrant development of PFC interneurons and a number of psychiatric disorders, mechanisms underlying the development of these neurons are poorly understood. Here we show that the retinoic acid (RA)-degrading enzyme CYP26B1 (cytochrome P450 family 26, subfamily B, member 1) is transiently expressed in the mouse frontal cortex during postnatal development, and that medial ganglionic eminence (MGE)-derived interneurons, particularly in parvalbumin (PV)-expressing neurons, are the main cell type that has active RA signaling during this period. We found that frontal cortex-specific Cyp26b1 knock-out mice had an increased density of PV-expressing, but not somatostatin-expressing, interneurons in medial PFC, indicating a novel role of RA signaling in controlling PV neuron development. The initiation of Cyp26b1 expression in neonatal PFC coincides with the establishment of connections between the thalamus and the PFC. We found that these connections are required for the postnatal expression of Cyp26b1 in medial PFC. In addition to this regionspecific role in postnatal PFC that regulates RA signaling and PV neuron development, the thalamocortical connectivity had an earlier role in controlling radial dispersion of MGE-derived interneurons throughout embryonic neocortex. In summary, our results suggest that the thalamus plays multiple, temporally separate roles in interneuron development in the PFC.

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The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex

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Keywords

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