| First Author | Kozuka T | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 3445 |
| PubMed ID | 30837489 | Mgi Jnum | J:276660 |
| Mgi Id | MGI:6307549 | Doi | 10.1038/s41598-019-38910-2 |
| Citation | Kozuka T, et al. (2019) miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation. Sci Rep 9(1):3445 |
| abstractText | 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. |
