Neuroscience
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The serotonergic metacerebral giant cell (C1) of Helix pomatia was isolated with its bifurcate axon and plated in culture under five conditions: (i) with no target; (ii) with the appropriate target B2 near the stump of the bigger branch (CBC); (iii) with B2 near the stump of the smaller branch (CC); (iv) with a wrong target (C3) near the stump of the CBC branch and (v) with B2 and C3 positioned near the CBC and CC stump, respectively. The counting of anti-serotonin antibody-labelled varicosities of the C1 neuron showed that the presence of the appropriate target in either axonal domain both down-regulated the number of varicosities of the contralateral neuritic field, and increased their average size, whereas the wrong target induced an overall reduction of the number of C1 neuron varicosities, and inhibited the evoked transmitter release. The action potential-evoked calcium concentration increase in the neuritic terminals of the C1 neuron cultured alone, or in presence of the appropriate target, reached a value significantly higher than that reached in presence of the wrong target. These results provide evidence that the postsynaptic neuron regulates both morphological and functional development of presynaptic terminals.
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Glial cell line-derived neurotrophic factor is one of the most potent motoneuron survival factors yet identified. Although retrograde transport of trophic factors to the cell body is thought to be an important process in motoneuron survival, the transport pathways that lead to interaction of glial cell line-derived neurotrophic factor with its receptors is not known. We have used a double ligated hypoglossal nerve preparation to investigate transport of endogenous glial cell line-derived neurotrophic factor and its receptors, glial cell line-derived neurotrophic factor family receptor alpha1 and receptor re-arranged during transfection. ⋯ Our results indicate anterograde transport of Schwann cell-derived glial cell line-derived neurotrophic factor, which is dependent on binding to its cell body-derived receptors. These findings suggest a mechanism for collection of glial cell line-derived neurotrophic factor from multiple Schwann cells which surround motor axons. We propose that in addition to its role in motoneuron survival, glial cell line-derived neurotrophic factor may also modulate local neuronal effects in distal regions of the nerve.
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The effect of noradrenaline was studied in principal neurons of the substantia nigra pars reticulata in rat brain slices using patch clamp recordings. Perfusion of noradrenaline or the alpha(1)-adrenoceptor agonist phenylephrine increased the spontaneous firing activity of reticulata cells. The alpha(1)-adrenoceptor antagonist prazosin counteracted the effects of noradrenaline. ⋯ It is suggested that noradrenaline increases the excitability of substantia nigra reticulata cells through alpha(1)-adrenoceptors. Both a reduction and an increase in membrane conductance may mediate this effect. The increase in the tonic firing of principal reticulata cells caused by noradrenaline may have significant consequences in regulating the final output of the basal ganglia and consequently in motor-related behaviours.
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The present study examined immunohistochemically the CNS distributions of a splice variant of the mu-opioid receptor, MOR-1D, in both rats and mice. In MOR-1D, exon 4 of MOR-1 is replaced by two additional exons that code for seven amino acids. Using rabbit antisera, we compared immunohistochemically the regional distribution of a C-terminal epitope of MOR-1D to that of a C-terminal epitope from MOR-1 and a C-terminal epitope from another splice variant, MOR-1C. ⋯ MOR-1D and MOR-1C are splice variants of the cloned mu-opioid receptor MOR-1. Although they differ only at the tip of the carboxy terminus, they show marked differences in their regional distributions, as determined immunohistochemically by epitopes in their unique carboxy termini. Since the splice variants are derived from the same gene, these differences in regional distribution imply region-specific messenger RNA processing.
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To determine whether initial nociceptive inputs caused by subcutaneous injection of formalin into the hindpaw are necessary and/or sufficient for allodynic behavior and microglial activation observed at one week following behavior, we examined Sprague-Dawley rats under five test conditions. Test condition 1. Formalin alone group (six rats), 5% formalin was injected subcutaneously into the dorsal side of the right hind paw. ⋯ The lumbar spinal cord was immunohistochemically processed at one week to assess the expression of a marker for activated microglia. The results showed: (i) pre-treatment with bupivacaine blocked both phases of formalin-evoked pain behaviors and the mechanical allodynia that developed one week post-formalin injection, but did not block microglial activation; (ii) treatment with bupivacaine 1h after formalin injection reduced paw edema and prevented skin ulceration, but one week allodynia and microglial activation were still present; and (iii) prolonged spinal microglial activation was not dependent on acute formalin-induced nociceptor activity, but was strongly associated with the amount of tissue destruction. Our studies suggest that: (i) the central sensitization associated with the phase II of formalin-evoked behaviors and spinal microglial activation are both necessary to permit the development of the long-term hyperalgesia produced by the subcutaneous administration of formalin into the rat's hindpaw; and (ii) acute nociceptive inputs following formalin injection are not necessary for central microglial activation that may be triggered by nerve damage or prolonged signals from peripherally inflamed tissue