Neuroscience
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Comparative Study
Characterization and regional distribution of strychnine-insensitive [3H]glycine binding sites in rat brain by quantitative receptor autoradiography.
Recent evidence suggests that a strychnine-insensitive glycine modulatory site is associated with the N-methyl-D-aspartate receptor-channel complex. A quantitative autoradiographic method was used to characterize the pharmacological specificity and anatomical distribution of strychnine-insensitive [3H]glycine binding sites in rat brain. [3H]Glycine binding was specific, saturable, reversible, pH and temperature-sensitive and of high affinity. [3H]Glycine interacted with a single population of sites having a KD of approximately 200 nM and a maximum density of 6.2 pmol/mg protein (stratum radiatum, CA1). Binding exhibited a pharmacological profile similar to the physiologically defined strychnine-insensitive glycine modulatory site. ⋯ The distribution of strychnine-insensitive [3H]glycine binding was heterogeneous with the following rank order of binding densities: hippocampus greater than cerebral cortex greater than caudate-putamen greater than or equal to thalamus greater than cerebellum greater than brain stem. This distribution of binding was correlated with N-methyl-D-aspartate-sensitive [3H]glutamate binding (r2 = 0.77; P less than 0.001; Pearson product-moment) and [3H]thienylcyclohexylpiperidine binding (r2 = 0.72; P less than 0.001). These observations are consistent with the hypothesis that the strychnine-insensitive glycine binding site is closely associated with the N-methyl-D-aspartate receptor-channel complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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The regional, cellular and subcellular distribution of GABA, GABA receptors and benzodiazepine receptors was investigated by light and electron microscopy in the human lumbar spinal cord taken post-mortem from eight cases aged 20-76 years. Firstly, the regional distribution of GABA receptors and benzodiazepine receptors was studied using autoradiography following in vitro labelling of cryostat sections with tritiated ligands. This was followed by a detailed study of the cellular and subcellular distribution and localization of GABA and benzodiazepine/GABAA receptors by light and electron microscopy using immunohistochemical techniques with monoclonal antibodies to GABA and to the alpha and beta subunits of the benzodiazepine/GABAA receptor complex. ⋯ Benzodiazepine/GABAA receptors were localized within the same types of synaptic complexes in which GABA-immunoreactive axon terminals were found. In these synaptic complexes, benzodiazepine/GABAA receptor immunoreactivity was associated with presynaptic and postsynaptic membranes and on apparent non-synaptic membranes. These results show a high concentration of GABA, GABA receptors and benzodiazepine receptors in lamina II of the dorsal horn of the human spinal cord and suggest a possible role for GABA in spinal sensory functions.
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Electrical stimulus intensity, capsaicin, excitatory amino acid antagonists and the substance P antagonist, spantide, have been used to investigate the roles of primary afferent C fibres and excitatory amino acid receptors in the generation of long duration (half time 9.1 s +/- 1.1 S. E. M., N = 24) contralateral reflexes recorded in ventral roots of immature rat spinal cords in vitro. ⋯ The depressant effect of spantide, unlike that of (+/-)-2-amino-5-phosphonopentanoic acid, was associated with a long lasting excitatory action. In the presence of tetrodotoxin (0.1 microM), spantide (33 microM) failed to antagonize substance P-induced depolarizations. It is suggested that long duration of the dorsal root-evoked contralateral ventral root potential is a consequence of the activation of the N-methyl-D-aspartate receptor operated ion channels by excitatory amino acid transmitters.
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We have examined the distribution of microglia in the normal adult mouse brain using immunocytochemical detection of the macrophage specific plasma membrane glycoprotein F4/80. We were interested to learn whether the distribution of microglia in the adult brain is related to regional variation in the magnitude of cell death during development and resulting monocyte recruitment, or whether the adult distribution is influenced by other local microenvironmental cues. We further investigated the possibility that microglia are sensitive to their microenvironment by studying their morphology in different brain regions. ⋯ They can be extremely elaborate and there is wide variation in the length and complexity of branching of the processes. There was no evidence of monocyte-like cells in the adult CNS. The systematic variation in microglial morphology provides further evidence that these cells are sensitive to their microenvironment.
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A major ascending nociceptive pathway from spinal lamina I to the mesencephalon has previously been reported in the cat, rat and monkey. In the present paper, we have used single and double retrograde labeling techniques to describe this projection system and its collateralization to the thalamus in the rat. Injections of wheat germ agglutinin-horseradish peroxidase into the pontomesencephalic parabrachial area labeled cell bodies bilaterally in lamina I and deeper laminae of the spinal cord. ⋯ The significance of these findings rest on previous work in this and other laboratories and concerns the understanding of spinal nociceptive mechanisms. Lamina I projection neurons are primarily nociceptive-specific in their response properties and have been shown to project to both the midbrain and thalamus via the dorsolateral funiculus in a number of species. The role of this projection system in nociceptive transmission may lie in its ability to distribute precise information to multiple brain stem sites which in turn activate autonomic or affective responses or descending pain modulatory mechanisms.