TY - JOUR
T1 - Nucleus accumbens pathways control cell-specific gene expression in the medial prefrontal cortex
AU - Hikida, Takatoshi
AU - Yao, Shuhei
AU - Macpherson, Tom
AU - Fukakusa, Ayumi
AU - Morita, Makiko
AU - Kimura, Haruhide
AU - Hirai, Keisuke
AU - Ando, Tatsuya
AU - Toyoshiba, Hiroyoshi
AU - Sawa, Akira
N1 - Funding Information:
We thank N. Otani, Y. Miyoshi for technical assistance. This work was supported by the Japan Society for the Promotion of Science KAKENHI grants (JP16H06568 and JP18H02542 to T.H.); Takeda Science Foundation, Uehara Memorial Foundation of Life Science, SENSHIN medical research foundation, and the International Collaborative Research Program of Institute for Protein Research, Osaka University, ICRa-19-03 (T.H.); Stanley, S-R, RUSK, NARSAD, and the National Institute of Health (MH-094268 Silvio O. Conte Center, MH-105660, MH-107730, and DA-040127) (A.S.); and partly supported by Takeda Pharmaceutical Company Limited.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The medial prefrontal cortex (mPFC) is a critical component of a cortico-basal ganglia-thalamo-cortical loop regulating limbic and cognitive functions. Within this circuit, two distinct nucleus accumbens (NAc) output neuron types, dopamine D1 or D2 receptor-expressing neurons, dynamically control the flow of information through basal ganglia nuclei that eventually project back to the mPFC to complete the loop. Thus, chronic dysfunction of the NAc may result in mPFC transcriptomal changes, which in turn contribute to disease conditions associated with the mPFC and basal ganglia. Here, we used RNA sequencing to analyse differentially expressed genes (DEGs) in the mPFC following a reversible neurotransmission blocking technique in D1 or D2 receptor-expressing NAc neurons, respectively (D1-RNB, or D2-RNB). Gene Set Enrichment Analysis revealed that gene sets of layer 5b and 6 pyramidal neurons were enriched in DEGs of the mPFC downregulated in both NAc D1- and D2-RNB mice. In contrast, gene sets of layer 5a pyramidal neurons were enriched in upregulated DEGs of the mPFC in D1-RNB mice, and downregulated DEGs of the mPFC in D2-RNB mice. These findings reveal for the first time that NAc output pathways play an important role in controlling mPFC gene expression.
AB - The medial prefrontal cortex (mPFC) is a critical component of a cortico-basal ganglia-thalamo-cortical loop regulating limbic and cognitive functions. Within this circuit, two distinct nucleus accumbens (NAc) output neuron types, dopamine D1 or D2 receptor-expressing neurons, dynamically control the flow of information through basal ganglia nuclei that eventually project back to the mPFC to complete the loop. Thus, chronic dysfunction of the NAc may result in mPFC transcriptomal changes, which in turn contribute to disease conditions associated with the mPFC and basal ganglia. Here, we used RNA sequencing to analyse differentially expressed genes (DEGs) in the mPFC following a reversible neurotransmission blocking technique in D1 or D2 receptor-expressing NAc neurons, respectively (D1-RNB, or D2-RNB). Gene Set Enrichment Analysis revealed that gene sets of layer 5b and 6 pyramidal neurons were enriched in DEGs of the mPFC downregulated in both NAc D1- and D2-RNB mice. In contrast, gene sets of layer 5a pyramidal neurons were enriched in upregulated DEGs of the mPFC in D1-RNB mice, and downregulated DEGs of the mPFC in D2-RNB mice. These findings reveal for the first time that NAc output pathways play an important role in controlling mPFC gene expression.
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U2 - 10.1038/s41598-020-58711-2
DO - 10.1038/s41598-020-58711-2
M3 - Article
C2 - 32020036
AN - SCOPUS:85078950739
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 1838
ER -