Immediate effects of maternal separation on the development of interneurons derived from medial ganglionic eminence in the neonatal mouse hippocampus.

Abstract

Aversive experiences, including maternal separation (MS), have been known as a risk for abnormal hippocampus development. Given that impairment of GABA inhibitory system is known as one of the common features of the abnormal hippocampal development induced by MS, we examined whether the MS on 4-day-old (P4) mice for 24hr abolishes the interneuron development. We observed that the MS reduced the volume of dorsal hippocampus on P14 as long-term effects. In addition, the MS decreased the number of parvalbumin (PV)-positive interneuron on P14 and P28 in the dorsal hippocampus. We further examined the immediate effects of MS by measuring the percentage of glutamic acid decarboxylase (GAD) 67-positive interneurons among the immature interneurons derived from medial ganglionic eminence (MGE) progenitors marked in nkx2.1cre;β-geo EGFP mice. During normal development from P4 to P5, the percentage of GAD67-positive interneurons among the MGE-derived interneurons in the dorsal hippocampus was significantly increased from 42.29% to 70.73% in the stratum pyramidale of the CA1 and increased from 46.4% to 56.99% in the stratum pyramidale of the CA2/3 region. However, the increase was not observed on P5 among the mice treated with the MS. These results suggest that the maturation of interneurons was suppressed by the MS. The suppressed maturation of interneurons may be one of the causes of the reduced volume of the hippocampus and PV+ interneurons observed in the hippocampus on P14 and P28 as a consequence of the MS during neonatal stage.