These studies and our results suggest that the stable expression of the NR2B gene is necessary for acquiring fear memory. Thus, the lack of fear acquisition in the FMCD group can be explained on the basis of the alternation in the expression of the NR2B subunit as well. Importantly, mice fed a diet supplemented with essential one-carbon nutrients after exposure to FMCD reversed their expression of the NR2B gene. Taking folate, methionine and choline might have normalized the alteration of one-carbon metabolism caused by exposure to FMCD. In addition to the reduced expression in the NR2B subunit gene, we found that the mRNA expression of Gabra2 was reduced in both experimental groups at 6 weeks. It is known that activating GABA signaling is crucial to the development of NMDA receptormediated neural activity during the maturation of the brain. The combination of decreased expressions of NMDA and GABA receptor genes might also have contributed to the imbalance between the excitatory/inhibitory neurotransmission via glutamate/GABA, which could lead to the alteration of reduced anxiety-like behaviors as well as the reduced fear acquisition in the experimental groups at 6 weeks. In addition, it is important to note that GABA transmission is initially excitatory but becomes inhibitory during the early postnatal period in rodents, and such maturation of GABAergic transmission is known to develop with increasing expression of chloride transporter KCC2. Because the food restriction in our experiments started at postnatal day 21, when the rodent hippocampus is still in the developmental stage, intracellular chloride homeostasis in the hippocampus of our experimental mice groups might have been altered due to the poor nutrition. Interestingly, ad libitum intake of a normal diet reversed the decreased expression of Gabra2 but also induced an increase in anxiety-like behavior ; in addition, persistently reduced hippocampal expression of Gabra3 was observed in the FMCD group. The expression of Gabra3 in the hippocampus is BAY 73-4506 relatively high compared to other brain regions, and the alterations in GABAA receptor subunit composition during the developmental period might influence later responses to stressors and adult neurogenesis, which could serve as a fundamental substrate of anxiety that appears in adulthood. Several limitations to the study should be noted. First, body weights were reduced by feeding the FMCD as shown in Figure 1. Rizki et al. revealed that feeding a methionine-cholinedeficient diet induced the loss of body weight and the gain of energy consumption. This observed weight loss might be due to lack of methionine, since a choline-folic acid-deficient diet with low methionine in a previous study did not induce weight loss. Second, food satiation is known to affect anxiety-like behavior. In our study, the FMCD group might have had food satiation, because this group had ad libitum access to the FCMD diet. In contrast, the FR group might not have had food satiation, because the FR group was fed a restricted amount of the normal diet. Thus, despite the anxiety-like behaviors being similar in the two experimental groups, some qualitative difference.