miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation

Takashi Kozuka, Yoshihiro Omori, Satoshi Watanabe, Etsuko Tarusawa, Haruka Yamamoto, Taro Chaya, Mayu Furuhashi, Makiko Morita, Tetsuya Sato, Shinichi Hirose, Yasuyuki Ohkawa, Yumiko Yoshimura, Takatoshi Hikida, Takahisa Furukawa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

MicroRNA-124 (miR-124) is evolutionarily highly conserved among species and one of the most abundantly expressed miRNAs in the developing and mature central nervous system (CNS). Previous studies reported that miR-124 plays a role in CNS development, such as neuronal differentiation, maturation, and survival. However, the role of miR-124 in normal brain function has not yet been revealed. Here, we subjected miR-124-1 +/− mice, to a comprehensive behavioral battery. We found that miR-124-1 +/− mice showed impaired prepulse inhibition (PPI), methamphetamine-induced hyperactivity, and social deficits. Whole cell recordings using prefrontal cortex (PFC) slices showed enhanced synaptic transmission in layer 5 pyramidal cells in the miR-124-1 +/− PFC. Based on the results of behavioral and electrophysiological analysis, we focused on genes involved in the dopaminergic system and identified a significant increase of Drd2 expression level in the miR-124-1 +/− PFC. Overexpression or knockdown of Drd2 in the control or miR-124-1 +/− PFC demonstrates that aberrant Drd2 signaling leads to impaired PPI. Furthermore, we identified that expression of glucocorticoid receptor gene Nr3c1, which enhances Drd2 expression, increased in the miR-124-1 +/− PFC. Taken together, the current study suggests that miR-124 dosage modulates PFC function through repressing the Drd2 pathway, suggesting a critical role of miR-124 in normal PFC function.

Original languageEnglish
Article number3445
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • General

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