Neuroscience
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Dopamine neurons of the ventral midbrain are activated transiently following stimuli that predict future reward. This response has been shown to signal the expected value of future reward, and there is strong evidence that it drives positive reinforcement of stimuli and actions associated with reward in accord with reinforcement learning models. Behavior is also influenced by reward uncertainty, or risk, but it is not known whether the transient response of dopamine neurons is sensitive to reward risk. ⋯ In a Pavlovian task, in which the neuronal responses to each stimulus could be measured in isolation, it was found that dopamine neurons were more strongly activated by the stimulus associated with reward risk. Given extensive evidence that dopamine drives reinforcement, these results strongly suggest that dopamine neurons can reinforce risk-seeking behavior (gambling), at least under certain conditions. Risk-seeking behavior has the virtue of promoting exploration and learning, and these results support the hypothesis that dopamine neurons represent the value of exploration.
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We have recorded, for the first time, in non-anesthetized, head-restrained mice, a total of 407 single units throughout the dorsal raphe nucleus (DR), which contains serotonin (5-hydroxytryptamine, 5-HT) neurons, during the complete wake-sleep cycle. The mouse DR was found to contain a large proportion (52.0%) of waking (W)-active neurons, together with many sleep-active (24.8%) and W/paradoxical sleep (PS)-active (18.4%) neurons and a few state-unrelated neurons (4.7%). The W-active, W/PS-active, and sleep-active neurons displayed a biphasic narrow or triphasic broad action potential. ⋯ Triphasic DR slow-wave sleep (SWS)-active and SWS/PS neurons were also characterized by slow firing. At the transition from sleep to waking, sleep-selective neurons with no discharge activity during waking ceased firing before onset of waking, while, at the transition from waking to sleep, they fired after onset of sleep. The present study shows a marked heterogeneity and functional topographic organization of both serotonergic and non-serotonergic mouse DR neurons and suggests that they play different roles in behavioral state control and the sleep/waking switch.
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Stem cells have a number of properties, which make them excellent candidates for the treatment of various neurologic disorders, the most important of which being their ability to migrate to and differentiate predictably at sites of pathology in the brain. The disease-directed migration and well-characterized differentiation patterns of stem cells may eventually provide a powerful tool for the treatment of both localized and diffuse disease processes within the human brain. A thorough understanding of the molecular mechanisms governing their migratory properties and their choice between different differentiation programs is essential if these cells are to be used therapeutically in humans. This review focuses on summarizing the migration and differentiation of therapeutic neural and mesenchymal stem cells in different disease models in the brain and also discusses the promise of these cells to eventually treat various forms of neurologic disease.
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Components of the brain's dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. ⋯ However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence.
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There is increasing evidence that pain transmission on one side of the body is influenced by a painful state on the other side. We have investigated this phenomenon by studying the activation pattern (using C-fos labeling) of spinal glycinergic and GABAergic (Gly/GABA) neurons after capsaicin injection in the ipsilateral hind paw of rats that were preconditioned with an acute or chronic pain stimulus in the contralateral hind paw or rats that were not preconditioned (control). For this purpose, fluorescent in situ hybridization with GlyT2 and GAD67 mRNA probes was combined with fluorescent C-fos immunohistochemistry. ⋯ This increase in C-fos activation of Gly/GABA neurons occurred without significant changes in the total number of C-fos activated neurons, and without any significant changes in the mechanical thresholds in the hind paws after capsaicin injection. The results showed that one-sided chronic pain, especially inflammation, significantly increases the C-fos activation pattern of spinal Gly/GABA neurons on the other side of the spinal cord. This further underlines the existence of a dynamic interaction between ipsi- and contralateral spinal neurons in the processing of nociceptive information.