Neuroscience
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Comparative Study
Role of postsynaptic density protein-95 in the maintenance of peripheral nerve injury-induced neuropathic pain in rats.
Our previous work has demonstrated that postsynaptic density protein-95, a molecular scaffolding protein that binds and clusters N-methyl-D-aspartate receptors at neuronal synapses, plays an important role in the development of peripheral nerve injury-induced neuropathic pain. The current study further investigated the possible involvement of postsynaptic density protein-95 in the maintenance of neuropathic pain. Mechanical and thermal hyperalgesia were induced within 3 days and maintained for 15 days or longer after unilateral injury to the fifth lumbar spinal nerve. ⋯ In addition, postsynaptic density protein-95 antisense oligodeoxynucleotide did not change locomotor activity of experimental animals. Our results indicate that the deficiency of postsynaptic density protein-95 protein in the spinal cord significantly attenuates nerve injury-induced mechanical and thermal hyperalgesia during both the development and maintenance of chronic neuropathic pain. These results suggest that postsynaptic density protein-95 might be involved in the central mechanisms of chronic neuropathic pain and provide a novel target for development of new pain therapies.
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Comparative Study
Desynchronisation of spontaneously recurrent experimental seizures proceeds with a single rhythm.
Here we investigate the temporal properties of recurrent seizure-like events (SLEs) in a low-[Mg(2+)] model of experimental epilepsy. Simultaneous intra- and extracellular electric signals were recorded in the CA3 region of rat hippocampal slices whereby cytosolic [Ca(2+)] transients were imaged by fluorescence detection. Recurrence pattern analysis was applied to give a measure of synchrony of simultaneously recorded intra- and extracellular electric signals and the SLE frequencies were extracted by complex wavelet analysis. ⋯ Release of gap junction blockade shortened both SLEs and their tonic phase indicating that persistent changes occurred via an altered gap junction coupling. We conclude that the initially precise temporal synchrony is gradually destroyed during ictal events with a single rhythm of continuously decreasing frequency. Blockade of gap junction coupling might prevent epileptic synchronisation.
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Comparative Study
Intrinsic collaterals of layer 6 Meynert cells and functional columns in primate V1.
Meynert cells are a distinct type of large neuron which project to area MT/V5 and to subcortical targets, including the superior colliculus. They have recently been shown to have extensive intrinsic collaterals spreading up to 8.0 mm within layer 6 of area V1 [J Comp Neurol 441 (2001) 134]. Using intrinsic signal imaging combined with tracer injections, this study investigates how Meynert cell collaterals are mapped in relation to the functional architecture of area V1 in macaque monkeys. ⋯ This contrasts with the same-eye bias previously reported for intrinsic collaterals of pyramidal neurons in layer 3. The suggestion is that the system of Meynert intrinsic collaterals is involved with binocular interactions over wide sectors of the visual field. This might be related to processes such as optic flow or, especially given the wide-field spread, even contour completion or interpolation.
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Comparative Study
Developmental regulation of the A-type potassium-channel current in hippocampal neurons: role of the Kvbeta 1.1 subunit.
The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvbeta 1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA. Whole-cell patch clamp recordings of rat hippocampal pyramidal neurons in primary culture showed a developmental decrease in the time constant of inactivation (tau(in)) of voltage-gated K+ currents: 17.9+/-1.5 ms in young neurons (5-7 days in vitro; n=53, mean+/-S. ⋯ This effect was most pronounced at -40 mV, where the ISI of the first pair of action potentials was nearly doubled. These data indicate that Kvbeta 1.1 contributes to the developmental control of IA in hippocampal neurons and that the magnitude of effect is sufficient to regulate electrical excitability. Viral-mediated antisense knockdown of Kvbeta 1.1 is capable of decreasing the electrical excitability of post-mitotic hippocampal neurons, suggesting this approach has applicability to gene therapy of neurological diseases associated with hyperexcitability.
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We recently reported that exogenously applied orphanin FQ, the endogenous ligand for opioid receptor-like 1 (ORL(1)) receptor, produces sex-specific modulation of trigeminal nociception, and that estrogen contributes to these sex-related differences. Estrogen could produce these sex-related differences by altering the expression of the ORL(1)-receptor gene in the trigeminal nucleus caudalis. Utilizing in situ hybridization, we compared levels of ORL(1) receptor mRNA and investigated its colocalization with estrogen receptor mRNA in trigeminal neurons. ⋯ Levels were reduced to proestrus levels in these regions following estradiol replacement. Our results also showed that ORL(1) receptor mRNA is present in majority of estrogen receptor (alpha and/or beta) mRNA-containing neurons. We conclude that there are sex-related differences in the ORL(1)-receptor gene expression in the trigeminal nucleus caudalis, which appear to be determined in part by estrogen levels.