Neuroscience
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Physical (exteroceptive) stimuli and emotional (interoceptive) stimuli are thought to influence stress-related physiologic and behavioral responses through different neural mechanisms. Previous studies have demonstrated that stress-induced activation of brainstem serotonergic systems is influenced by environmental factors such as temperature. In order to further investigate the effects of environmental influences on stress-induced activation of serotonergic systems, we exposed adult male Wistar rats to either home cage control conditions or a 15-min swim in water maintained at 19 °C, 25 °C, or 35 °C and conducted dual immunohistochemical staining for c-Fos, a marker of immediate-early nuclear activation, and tryptophan hydroxylase (TPH), a marker of serotonergic neurons. ⋯ In addition, exposure to cold (19 °C) swim, relative to 35 °C swim, increased c-Fos expression in the dorsal raphe nucleus, ventrolateral part/periaqueductal gray (DRVL/VLPAG) and dorsal raphe nucleus, interfascicular part (DRI). Both of these subregions of the dorsal raphe nucleus (DR) have previously been implicated in thermoregulatory responses. Altogether, the data are consistent with the hypothesis that midbrain serotonergic neurons, possibly via activation of afferents to the DR by thermosensitive spinoparabrachial pathways, play a role in integration of physiologic and behavioral responses to interoceptive stress-related cues involved in forced swimming and exteroceptive cues related to cold ambient temperature.
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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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Grey matter volume correlates with virtual water maze task performance in boys with androgen excess.
Major questions remain about the specific role of testosterone in human spatial navigation. We tested 10 boys (mean age 11.65 years) with an extremely rare disorder of androgen excess (Familial Male Precocious Puberty, FMPP) and 40 healthy boys (mean age 12.81 years) on a virtual version of the Morris Water Maze task. In addition, anatomical magnetic resonance images were collected for all patients and a subsample of the controls (n=21) after task completion. ⋯ Group differences in correlations of performance with GMV were apparent in medial regions of the prefrontal cortex as well as the middle occipital gyrus and the cuneus. By comparison, similar correlations for both groups were found in the inferior parietal lobule. These data provide novel insight into the relation between testosterone and brain development and suggest that morphological differences in a spatial navigation network covary with performance in spatial ability.
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During the development of epilepsy in adult animals, newly generated granule cells integrate abnormally into the hippocampus. These new cells migrate to ectopic locations in the hilus, develop aberrant basal dendrites, contribute to mossy fiber sprouting, and exhibit changes in apical dendrite structure and dendritic spine number. Mature granule cells do not appear to exhibit migration defects, basal dendrites, and mossy fiber sprouting, but whether they exhibit apical dendrite abnormalities or spine changes is not known. ⋯ In contrast to immature granule cells, exposing mature granule cells to status epilepticus did not significantly disrupt the branching structure of their apical dendrites. Mature granule cells did, however, exhibit significant reductions in spine density and spine number relative to age-matched cells from control animals. These data demonstrate that while mature granule cells are resistant to developing the gross structural abnormalities exhibited by younger granule cells, they show similar plastic rearrangement of their dendritic spines.
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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.