ABSTRACT
Deprivation of maternal care during early development markedly affects emotional development, but the underlying neuromolecular mechanisms are not fully understood. In a mouse model of disrupted mother-infant relationship, early weaning causes long-term impacts on pups to exhibit increased corticosterone secretion, anxiety, and stress responses in their adulthood. Revealing the molecular mechanisms behind it would beneficial to ameliorating mental problems caused by abuse in childhood. We report that normalizing circulating corticosterone in early-weaned mice, either in adulthood or soon after weaning, ameliorated anxiety levels assessed in the plus maze test. Administering a glucocorticoid receptor antagonist into the prefrontal cortex (PFC) reversed the effects of early weaning, whereas administering corticosterone increased anxiety levels, suggesting that the PFC is corticosterone's target brain region. In the PFCs of early-weaned mice, we observed prolonged reductions in the expression of brain-derived neurotrophic factor (BDNF) and associated mRNAs. Anxiety in early-weaned mice was ameliorated by pretreatment with BDNF or a BDNF receptor agonist. In summary, early weaning increased anxiety levels by modulating glucocorticoid and BDNF signaling in the PFC.
Subject(s)
Anxiety/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Prefrontal Cortex/metabolism , Signal Transduction/physiology , Animals , Animals, Newborn , Corticosterone/metabolism , Disease Models, Animal , Female , Maternal Deprivation , Mice , Mice, Inbred ICR , Stress, Psychological/metabolism , WeaningABSTRACT
Fox odour 2,4,5-trimethyl thiazoline (TMT) is known to activate multiple glomeruli in the mouse olfactory bulb (OB) and elicits strong fear responses. In this study, we screened TMT-reactive odourant receptors and identified Olfr1019 with high ligand reactivity and selectivity, whose glomeruli are located in the posterodorsal OB. In the channelrhodopsin knock-in mice for Olfr1019, TMT-responsive olfactory-cortical regions were activated by photostimulation, leading to the induction of immobility, but not aversive behaviour. Distribution of photoactivation signals was overlapped with that of TMT-induced signals, but restricted to the narrower regions. In the knockout mice, immobility responses were reduced, but not entirely abolished likely due to the compensatory function of other TMT-responsive glomeruli. Our results demonstrate that the activation of a single glomerular species in the posterodorsal OB is sufficient to elicit immobility responses and that TMT-induced fear may be separated into at least two different components of immobility and aversion.
Subject(s)
Fear/drug effects , Freezing Reaction, Cataleptic/drug effects , Olfactory Bulb/drug effects , Olfactory Perception/physiology , Receptors, Odorant/genetics , Smell/physiology , Thiazoles/pharmacology , Animals , Aversive Agents/isolation & purification , Aversive Agents/pharmacology , Behavior, Animal/drug effects , Channelrhodopsins/genetics , Channelrhodopsins/metabolism , Fear/psychology , Feces/chemistry , Foxes , Freezing Reaction, Cataleptic/physiology , Gene Expression , Gene Knock-In Techniques , Male , Mice , Odorants/analysis , Olfactory Bulb/physiology , Photic Stimulation , Receptors, Odorant/metabolism , Stereotaxic Techniques , Thiazoles/isolation & purificationABSTRACT
Large-scale transmission gratings were produced for a stretcher and a compressor in the Yb-fiber chirped-pulse amplification system. A 23-W, 200-fs laser system with a 10-MHz repetition rate was demonstrated. Focused intensity as high as 10(14) W/cm(2) was achieved, which is high enough for multi-photon processes such as high-order harmonics generation and multi-photon ionization of neutral atoms. High-order harmonics up to 7th order were observed using Xe gas as a nonlinear medium.
