Neuroscience
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Cytokines in brain contribute to the regulation of physiological processes and complex behavior, including sleep. The cytokines that have been most extensively studied with respect to sleep are interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6. Administration of these cytokines into laboratory animals, or in some cases into healthy human volunteers, increases the amount of time spent in non-rapid eye movement (NREM) sleep. ⋯ No mouse received more than two doses of muIL-1beta, and administration of muIL-1beta doses was counter-balanced to eliminate potential order effects. Sleep-wake behavior was determined for 24 h after injections. i.c.v. administration of muIL-1beta increased in NREM sleep of both mouse strains in a dose-related fashion, but the maximal increase was of greater magnitude in C57Bl/6J mice. muIL-1beta induced fever in C57Bl/6J mice but not in IL-6 KO mice. Collectively, these data demonstrate IL-6 is necessary for IL-1 to induce fever, but IL-6 is not necessary for IL-1 to alter NREM sleep.
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Selective immunotoxic cholinergic lesions in the nucleus basalis magnocellularis (NBM) impair visuospatial attention performance in a 5-choice serial reaction time task (5-CSRT task). The features of the reported deficits, however, do not perfectly match among studies, in which some lesions may have been too weak while others largely encroached onto the septal region. Using the 5-CSRT task, we therefore re-assessed the effects of NBM lesions that produced minimal septal damage. ⋯ Furthermore, overall performance levels decreased when the stimulus duration was shortened (i.e. 0.5-0.2 s) or its intensity attenuated, and rats with cholinergic lesions remained consistently impaired vs. controls. These results show that disruption of sustained visual attention functions by damage to the NBM cholinergic neurons can be evidenced despite weak or no effects on variables accounting for motivational, locomotion- or impulsivity-related biases. Discrepancies with previously reported results are discussed in terms of differences in lesion extent/specificity and training levels.
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The neurosteroid allopregnanolone (3alpha,5alpha-THP) is well characterized as a potentially therapeutic molecule which exerts important neurobiological actions including neuroprotective, antidepressant, anxiolytic, anesthetic and analgesic effects. We have recently observed that neurons and glial cells of the rat spinal cord (SC) contain various key steroidogenic enzymes such as 5alpha-reductase and 3alpha-hydroxysteroid oxido-reductase which are crucial for 3alpha,5alpha-THP biosynthesis. Furthermore, we demonstrated that the rat SC actively produces 3alpha,5alpha-THP. ⋯ These results demonstrate that glycine and gelsemine, acting via Gly-R, upregulate 3alpha,5alpha-THP biosynthesis in the SC. The data also revealed a structure-activity relationship of the analogs strychnine and gelsemine on neurosteroidogenesis. Possibilities are opened for glycinergic agents and gelsemine utilization to stimulate selectively 3alpha,5alpha-THP biosynthetic pathways in diseases evoked by a decreased neurosteroidogenic activity of nerve cells.
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The ventral tegmental area (VTA) is a nodal link in reward circuitry. Based on its striatal output, it has been subdivided in a caudomedial part which targets the ventromedial striatum, and a lateral part which targets the ventrolateral striatum [Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56:27-78]. ⋯ In general, these projections, like the spiralated striato-nigro-striatal loops, display a medial-to-lateral organization. This anatomical arrangement conceivably permits the ventromedial striatum to influence the activity of the lateral striatum. The caudal pole of the VTA appears to be a critical site for a global recruitment of the mesotelencephalic system.
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Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. ⋯ Vesicular glutamate transporter 2 mRNA-positive neurons were present in the ventral tegmental area, but not substantia nigra or retrorubral field. They were mainly confined to the rostro-medial region of the ventral tegmental area, and represented approximately 2-3% of the total neurons counted ( approximately 1600 cells). These results demonstrate that GABAergic and glutamatergic neurons represent large proportions of the neurons in what are traditionally considered as dopamine nuclei and that there are considerable heterogeneities in the proportions of cell types in the different dopaminergic midbrain regions.