There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7±3.4%) than in control offspring (42.1±6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2±5.0%) than in control offspring (16.4±3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7–8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring.

To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses revealed that both mRNA species were highly concentrated in the geniculorecipient layers IVA and IVC, where they were coexpressed in the same neurons. Monocular inactivation by tetrodotoxin injection resulted in a strong and rapid (<3 h) downregulation of these mRNAs, suggesting the retinal activity dependency of their expression. Consistent with the high expression level in V1, clear modulatory effects of 5-HT1B and 5-HT2A receptor agonists on the responses of V1 neurons were observed in in vivo electrophysiological experiments. The modulatory effect of the 5-HT1B agonist was dependent on the firing rate of the recorded neurons: The effect tended to be facilitative for neurons with a high firing rate, and suppressive for those with a low firing rate. The 5-HT2A agonist showed opposite effects. These results suggest that this serotonergic system controls the visual response in V1 for optimization of information processing toward the incoming visual inputs.

The neocortex consists of histochemically, connectionally, and functionally distinguishable areas. Recently, molecular biological techniques have enabled us to find rare types of genes expressed in specific neocortical areas. We previously reported occ1 gene as preferentially expressed in the primary visual cortex (V1), using the differential display method. Here, by differential display, we found selective and strong expression of the serum retinol-binding protein (RBP) gene, in higher-order association areas. In V1, RBP mRNA was expressed only in the superficial part of layer II, but its expression increased, involving deeper layers, along the visual pathway. In visual association areas such as TE, RBP mRNA was strongly expressed in both supra- and infragranular layers. In primary auditory and somatosensory areas, as in V1, RBP expression was low, and restricted to the upper part of the supragranular layers. The laminar pattern of RBP expression is in marked contrast with that of occ1; and in early visual areas where both genes are expressed, these occur in distinct sublayers within the supragranular layers. In neonatal monkeys, the area-specific expression pattern of RBP was less distinct, suggesting that the characteristic expression of RBP in higher-order association areas is mainly established postnatally.