Neuroscience
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It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal pathway plays an important role in learning and memory processing, and that the development of this transmitter pathway is influenced by neurotrophic factors. Although some of these factors have been discovered, the regulatory mechanisms for this developmental event have not been fully elucidated. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC-NE neurons. ⋯ NE fiber innervation into the hippocampal co-transplant from an adjacent brainstem graft was also influenced by the presence of GDNF, with a significantly more robust innervation observed in transplants from wildtype fetuses. The most successful LC/hippocampal co-grafts were generated from fetuses expressing the wildtype GDNF background, whereas the most severely affected transplants were derived from double transplants from null-mutated fetuses. Our data suggest that development of the NE LC-hippocampal pathway is dependent on the presence of GDNF, most likely through a target-derived neurotrophic function.
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Each day, approximately 0.5-0.9 l of water diffuses through (primarily) aquaporin-1 (AQP1) channels in the human choroid plexus, into the cerebrospinal fluid of the brain ventricles and spinal cord central canal, through the ependymal cell lining, and into the parenchyma of the CNS. Additional water is also derived from metabolism of glucose within the CNS parenchyma. To maintain osmotic homeostasis, an equivalent amount of water exits the CNS parenchyma by diffusion into interstitial capillaries and into the subarachnoid space that surrounds the brain and spinal cord. ⋯ Using improved shadowing methods, we demonstrate sub-molecular cross-bridges that link the constituent intramembrane particles (IMPs) into regular square lattices of AQP4 arrays. We show that the AQP4 core particle is 4.5 nm in diameter, which appears to be too small to accommodate four monomeric proteins in a tetrameric IMP. Several structural models are considered that incorporate freeze-fracture data for submolecular "cross-bridges" linking IMPs into the classical square lattices that characterize, in particular, naturally occurring AQP4.
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Polyimide regenerative electrodes (RE) constitute a promising neural interface to selectively stimulate regenerating fibers in injured nerves. The characteristics of the regeneration through an implanted RE, however, are only beginning to be established. It was recently shown that the number of myelinated fibers distal to the implant reached control values 7 months postimplant; however, the functional recovery remained substantially below normal [J Biomed Mater Res 60 (2002) 517]. ⋯ Moreover, smaller ganglion cells regenerated better than large neurons by a significant 13.8%. These results indicate that the RE is not an obstacle for the re-growth of sensory fibers, but partially hinders fiber regeneration from motoneurons. They also suggest that fine fibers may be at an advantage over large ones to regenerate through the RE.
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Neurokinins such as substance P and neurokinin A have long been thought to act as neurotransmitters or modulators in the nucleus tractus solitarius. However, the role and location of the receptors for these peptides have remained unclear. We examined the consequences of activation of the neurokinin-1 (NK1) receptor subtype in the rat nucleus tractus solitarius using whole-cell patch clamp recordings in brain slices. ⋯ The increase in GABA release was also shown to be protein kinase C-dependent. The data presented here show NK1 receptors in the rat nucleus tractus solitarius are present both excitatory and inhibitory neurons. Activation of these receptors can result in increases in release of both GABA and glutamate, suggesting a crucial modulatory role for NK1 receptors in the rat nucleus tractus solitarius.
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In vivo microdialysis was used to determine the necessity of neuronal activity in the nucleus accumbens (NAC) for task-induced increases in cortical acetylcholine (ACh) efflux. Rats were trained in a behavioral task in which they were required to perform a defined number of licks of a citric acid solution in order to gain access to a palatable, cheese-flavored food. Upon reaching a consistent level of performance, rats were implanted with microdialysis cannula in the medial prefrontal cortex (mPFC) and either the ipsilateral shell of the NAC or in the dorsal striatum (STR; control site). ⋯ Administration of TTX into the dorsal STR control site was ineffective in blocking performance-associated increases in cortical ACh. The D2 antagonist sulpiride (10 or 100 microM) administered into the NAC via reverse dialysis was ineffective in blocking increases in cortical ACh efflux. The present data reveal that neuronal activity in the NAC is necessary for behaviorally induced increases in cortical ACh efflux and that this activation does not require increases in D2 receptor activity.