Central serotonin (5-HT) dysregulation contributes to the susceptibility for mental disorders, including depression, anxiety, and posttraumatic stress disorder, and learning and memory deficits. We report that the formation of hippocampus-dependent spatial memory is compromised, but the acquisition and retrieval of contextual fear memory are enhanced, in central 5-HT-deficient mice. Genetic deletion of serotonin in the brain was achieved by inactivating Lmx1b selectively in the raphe nuclei of the brainstem, resulting in a near-complete loss of 5-HT throughout the brain. These 5-HT-deficient mice exhibited no gross abnormality in brain structures and had normal locomotor activity. Spatial learning in the Morris water maze was unaffected, but the retrieval of spatial memory was impaired. In contrast, contextual fear learning and memory induced by foot-shock conditioning was markedly enhanced, but this enhancement could be prevented by intracerebroventricular administration of 5-HT. Foot shock impaired longterm potentiation and facilitated long-term depression in hippocampal slices in WT mice but had no effect in 5-HT-deficient mice. Furthermore, bath application of 5-HT in 5-HT-deficient mice restored foot shock-induced alterations of hippocampal synaptic plasticity. Thus, central 5-HT regulates hippocampus-dependent contextual fear memory, and 5-HT modulation of hippocampal synaptic plasticity may be the underlying mechanism. The enhanced fear memory in 5-HT-deficient mice supports the notion that 5-HT deficiency confers susceptibility to posttraumatic stress disorder in humans.hippocampus ͉ long-term depression ͉ long-term potentiation ͉ anxiety T he neurotransmitter serotonin (5-HT) exerts a wide spectrum of actions in the nervous system by modulating neural development, synaptic plasticity, pain sensation, rhythm, food intake, and a variety of behaviors (1-4). It has been proposed that perturbation of the 5-HT level in the brain contributes to depression and anxiety, and posttraumatic stress disorder (PTSD) (5-8), which are often accompanied by learning and memory deficits (9-11). The hippocampus is known to be critical for the formation of spatial and contextual fear memories (12-15), and the retrieval of hippocampus-dependent memories was found to be impaired in patients with depression and PTSD (16)(17)(18). Recent studies have also implicated the hippocampus as one of the primary sites for antidepressants (6,(19)(20)(21)(22)(23). Aversive stimuli such as foot shock that led to anxiety, depression, and fear memory in rodents also altered activity-dependent hippocampal synaptic plasticity (24)(25)(26)(27)(28)(29). Because the modulation of 5-HT activity altered hippocampal long-term potentiation (LTP) and long-term depression (LTD) (30-32), it is possible that perturbation of 5-HT level in the brain may affect hippocampusdependent learning and memory, and changes in hippocampal synaptic plasticity may also contribute to mental disorders, including anxiety and fear memory.Inhibitors of 5-HT biosynthesis that...

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The viability of recalcitrant seeds is lost following stress from either drying or freezing. Reactive oxygen species (ROS) resulting from uncontrolled metabolic activity are likely responsible for seed sensitivity to drying. Nitric oxide (NO) and the ascorbate-glutathione cycle can be used for the detoxification of ROS, but their roles in the seed response to desiccation remain poorly understood. Here, we report that desiccation induces rapid accumulation of H2O2, which blocks recalcitrant Antiaris toxicaria seed germination; however, pretreatment with NO increases the activity of antioxidant ascorbate-glutathione pathway enzymes and metabolites, diminishes H2O2 production and assuages the inhibitory effects of desiccation on seed germination. Desiccation increases the protein carbonylation levels and reduces protein S-nitrosylation of these antioxidant enzymes; these effects can be reversed with NO treatment. Antioxidant protein S-nitrosylation levels can be further increased by the application of S-nitrosoglutathione reductase inhibitors, which further enhances NO-induced seed germination rates after desiccation and reduces desiccation-induced H2O2 accumulation. These findings suggest that NO reinforces recalcitrant seed desiccation tolerance by regulating antioxidant enzyme activities to stabilize H2O2 accumulation at an appropriate concentration. During this process, protein carbonylation and S-nitrosylation patterns are used as a specific molecular switch to control antioxidant enzyme activities.