Neuroscience
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Comparative Study
Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.
Adenosine A2 receptors were labeled and visualized by autoradiography in tissue sections of the human brain using the A2-selective agonist ligand [3H](2-p-(2-carboxyethyl)phenylamino)-5'-N-carboxamidoadenosine (CGS 21680). The binding of this ligand was of high affinity, reversible, and was blocked by adenosine A2 agents. Autoradiographic mapping of adenosine A2 sites revealed them to be exclusively restricted to the caudate nucleus, putamen, nucleus accumbens, olfactory tubercle and the lateral segment of the globus pallidus. ⋯ In contrast, density values of A2 sites were dramatically decreased, compared to control values, in the basal ganglia of patients with Huntington's chorea. Similar losses of A2 receptors were observed in the guinea-pig striatum after local application of quinolinic acid while lesioning of the dopaminergic neurons was without effect. All these results taken together suggest that adenosine A2 receptors are localized on striatal output neurons which degenerate in Huntington's chorea.
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Following a set of studies concerning the intrinsic electrophysiology of mammalian central neurons in relation to global brain function, we reach the following conclusions: (i) the main difference between wakefulness and paradoxical sleep lies in the weight given to sensory afferents in cognitive images; (ii) otherwise, wakefulness and paradoxical sleep are fundamentally equivalent brain states probably subserved by an intrinsic thalamo-cortical loop. From this assumption, we conclude that wakefulness is an intrinsic functional realm, modulated by sensory parameters. In support of this hypothesis, we review morphological studies of the thalamocortical system, which indicate that only a minor part of its connectivity is devoted to the transfer of direct sensory input. ⋯ These considerations lead us to challenge the traditional Jamesian view of brain function according to which consciousness is generated as an exclusive by-product of sensory input. Instead, we argue that consciousness is fundamentally a closed-loop property, in which the ability of cells to be intrinsically active plays a central role. We further discuss the importance of spatial and temporal mapping in the elaboration of cognitive and perceptual constructs.
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Comparative Study
Aspartate-like immunoreactivity in primary afferent neurons.
There is now good evidence that amino acids act as neurotransmitters in primary afferent neurons of dorsal root ganglia. Glutamate is the primary candidate for such a role, and there are reasons to believe that release of glutamate may be accompanied by the release of other neuroactive substances. Using immunocytochemical techniques, we have tested the hypothesis that some dorsal root ganglion neurons contain elevated levels of aspartate as well as glutamate. ⋯ The presence of high levels of aspartate in terminals located in the superficial laminae of the dorsal horn was verified by pre- and post-embedding immunocytochemistry with the electron microscope. Aspartate was demonstrated in scalloped terminals, including dark scalloped terminals believed to be associated with unmyelinated fibers of nociceptors. This evidence supports the hypothesis that aspartate as well as glutamate is present in the cell bodies and terminals of nociceptive primary afferents, and may be released by the terminals of these afferents to activate neurons in the superficial laminae of the dorsal horn.
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The effect of capsaicin on voltage-activated calcium currents was investigated in voltage-clamped somata of cultured adult rat dorsal root ganglion neurons. About half the neurons studied were sensitive to capsaicin, which induced an inward current at negative membrane potentials accompanied by an increase in membrane conductance. In the sensitive neurons capsaicin inhibited voltage-activated calcium current to an extent that depended on the size and duration of the capsaicin-induced inward current. ⋯ Substituting Ca with Co did not prevent the prolonged block of calcium channels. It is concluded that the inhibition of voltage-activated calcium currents by capsaicin is secondary to increased intracellular Ca levels due to calcium entry through capsaicin-activated cation-specific ion channels in the plasma membrane. Long-lasting inhibition of voltage-activated calcium channels may contribute to the mechanism of the analgesic and anti-inflammatory effects of capsaicin through inhibition of neurotransmitter release from central and peripheral terminals of primary afferent nociceptive neurons.
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When the brain temperature was lowered by 2 degrees C from normothermic temperature, a protective effect on postischemic neuronal death was exhibited and levels of extracellular glutamate were attenuated to about half of those at normothermic brain temperature in the gerbil hippocampus. Hypothermia has been reported to confer a protective effect on ischemia-induced delayed neuronal death. The present study was carried out to quantify this protective effect of hypothermia on the degree of alteration in extracellular release of glutamate during ischemia and the final histopathological outcome in the hippocampus. ⋯ No CA1 ischemic neuronal damage was seen in 60% of gerbils at 35 degrees C and none was seen in any gerbils at 33 and 31 degrees C. In animals whose brain temperature was maintained at 39 degrees C during ischemia, the release of glutamate was slightly higher than that at 37 degrees C, and a high mortality rate of animals (75%) was observed. Our results reinforce other recent evidence suggesting that one of the mechanisms by which lowering of the brain temperature by only a few degrees during ischemia exerts a protective effect in the hippocampus, involves the reduction of ischemia-induced glutamate release.