Punishment-Predictive Cues Guide Avoidance through Potentiation of Hypothalamus-to-Habenula Synapses.

Throughout life, individuals learn to predict a punishment via its association with sensory stimuli. This process ultimately prompts goal-directed actions to prevent the danger, a behavior defined as avoidance. Neurons in the lateral habenula (LHb) respond to aversive events as well as to environmental cues predicting them, supporting LHb contribution to cue-punishment association. However, whether synaptic adaptations at discrete habenular circuits underlie such associative learning to instruct avoidance remains elusive. Here, we find that, in mice, contingent association of an auditory cue (tone) with a punishment (foot shock) progressively causes cue-driven LHb neuronal excitation during avoidance learning. This process is concomitant with the strengthening of LHb AMPA receptor-mediated neurotransmission. Such a phenomenon occludes long-term potentiation and occurs specifically at hypothalamus-to-habenula synapses. Silencing hypothalamic-to-habenulainputs or optically inactivating postsynaptic AMPA receptors within the LHb disrupts avoidance learning. Altogether, synaptic strengthening at a discrete habenular circuit transforms neutral stimuli into salient punishment-predictive cues to guide avoidance.

Intestinal Microbiota Profiles of Healthy Pre-School and School-Age Children and Effects of Probiotic Supplementation.

OBJECTIVES: This study aims to establish the baseline profile of intestinal microbiota in pre-school and school-age Japanese children and to investigate the effects of a probiotic on the microbiota. METHODS: We analyzed the intestinal microbiota and investigated the effects (before, during and after the ingestion period) on intestinal microbiota and the environment of 6 months of daily ingestion of a probiotic (Lactobacillus casei strain Shirota (LcS)-fermented milk). RESULTS: We performed an open trial in 23 children (14 boys, 9 girls; age 7.7 ± 2.4 years (mean ± SD); BMI 19.6 ± 4.6). The composition of intestinal microbiota of healthy pre-school and school-age children resembled that of adults. During probiotic supplementation, the population levels of Bifidobacterium and total Lactobacillus increased significantly, while those of Enterobacteriaceae, Staphylococcus and Clostridium perfringens decreased significantly. A significant increase in fecal concentrations of organic acids and also a decrease in fecal pH were observed during the ingestion period. However, the patterns of fecal microbiota and intestinal environment were found to revert to the baseline levels (i.e. before ingestion) within 6 months following the cessation of probiotic intake. CONCLUSION: Regular intake of an LcS-containing probiotic product may modify the gut microbiota composition and intestinal environment in pre-school and school-age children while maintaining the homeostasis of the microbiota.