Neuroscience
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Basic fibroblast growth factor (bFGF) is an important mitogen and neurotrophic factor that binds and signals through the high-affinity receptor, fibroblast growth factor receptor 1 (FGFR1). However, only a limited amount of information is available concerning the molecular forms and anatomical distribution of fibroblast growth factors (FGFs) in the normal human brain. We found multiple bFGF and FGFR1 mRNA transcripts which vary in expression pattern across human brain regions. ⋯ In contrast to FGFR1, bFGF mRNA expression was detected at very low levels in a small fraction of the neurons in the human hippocampus and caudal ERC. While bFGF mRNA may be expressed at low levels in neurons, bFGF-immunopositive cells with astrocytic features were detected throughout the mesial temporal lobe in rats, monkeys and humans. bFGF immunoreactive processes are found traversing the dentate gyrus, and bFGF immunoreactive cells are found in the neurogenic subgranular zone in all three mammalian species studied. The anatomical distribution of these two FGF family members suggests that bFGF is endogenously positioned to be involved in ongoing neurogenesis in the adult hippocampus, and that FGF trophic signaling to differentiated neurons could involve the release of astrocytic bFGF acting on neuronal FGFR1 in the normal adult human hippocampus.
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The lateral hypothalamus is part of an efferent system that modifies pain at the spinal cord dorsal horn, but the mechanisms by which lateral hypothalamus-induced antinociception occur are not fully understood. Previous work has shown that antinociception produced from electrical stimulation of the lateral hypothalamus is mediated in part by spinally projecting 5-hydroxytryptamine (5-HT) neurons in the ventromedial medulla. To further examine the role of the lateral hypothalamus in antinociception, the cholinergic agonist carbamylcholine chloride (125 nmol) was microinjected into the lateral hypothalamus of female Sprague-Dawley rats and nociceptive responses measured on the tail-flick and foot-withdrawal tests. ⋯ Lateral hypothalamus stimulation with carbamylcholine chloride produced significant antinociception that was blocked by WAY 100135, tropisetron, and SB-224289 on both the tail-flick and foot-withdrawal tests. Methysergide was not different from controls on the tail flick test, but increased foot-withdrawal latencies compared with controls. These results suggest that the lateral hypothalamus modifies nociception in part by activating spinally projecting serotonin neurons that act at 5-HT1A, 5-HT1B, and 5-HT3 receptors in the dorsal horn.
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Injury to the adult CNS often involves death of motoneurons, resulting in the paralysis and progressive atrophy of muscle. There is no effective therapy to replace motoneurons in the CNS. Our strategy to replace neurons and to rescue denervated muscles is to transplant dissociated embryonic day 14-15 (E14-15) ventral spinal cord cells into the distal stump of a peripheral nerve near the denervated muscles. ⋯ FK506-treated muscles were significantly more fatigue resistant than naive control muscles. FK506-treated muscles also had significantly stronger motor units than those in SB203580 or saline-treated muscles. These data suggest that a pathway regulated by FK506 improves the function of muscles reinnervated by embryonic neurons placed in peripheral nerve.
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The globus pallidus receives its major glutamatergic input from the subthalamic nucleus and subthalamic nucleus neurons synthesize CB1 cannabinoid receptors. The hypothesis of the present work was that CB1 receptors are localized in terminals of subthalamo-pallidal glutamatergic axons and that their activation leads to presynaptic modulation of neurotransmission between these axons and globus pallidus neurons. Patch-clamp studies were carried out on oblique-sagittal mouse brain slices. ⋯ Cannabinoids seem to act preferentially presynaptically: in contrast to their action on axon terminals, they have no effect on somadendritic receptors regulating firing rate. Cannabinoids elicit catalepsy in vivo. The observed inhibition of glutamatergic neurotransmission in the globus pallidus would favor catalepsy.
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Comparative Study
Sleep-dependent motor memory plasticity in the human brain.
Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. ⋯ Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.