Neuroscience
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Comparative Study
Atp2b2, encoding plasma membrane Ca2+-ATPase type 2, (PMCA2) exhibits tissue-specific first exon usage in hair cells, neurons, and mammary glands of mice.
Atp2b2 encodes the plasma membrane Ca(2+)-ATPase type 2 (PMCA2) expressed in various tissues, including stereocilia of cochlear and vestibular hair cells, cerebellar Purkinje cells, and lactating mammary epithelia. Mutations of the gene lead to deafness, ataxia, and reduced Ca(2+) levels in milk. Heterozygous mutants also have abnormal hearing, suggesting that precise regulation of Atp2b2 is required for normal function. ⋯ The regions around the mu and delta first exons are highly conserved between rat and mouse, but less so with other species. Our results show that expression of Atp2b2 is highly regulated, using four different transcriptional start regions, two of which are differentially expressed in neuronal tissue. This suggests that unique regulatory mechanisms are used to control Atp2b2 expression in different types of cells.
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Comparative Study
The dynamic range and domain-specific signals of intracellular calcium in photoreceptors.
Vertebrate photoreceptors consist of strictly delimited subcellular domains: the outer segment, ellipsoid, cell body and synaptic terminal, each hosting crucial cellular functions, including phototransduction, oxidative metabolism, gene expression and transmitter release. We used optical imaging to explore the spatiotemporal dynamics of Ca(2+) signaling in non-outer segment regions of rods and cones. Sustained depolarization, designed to emulate photoreceptor activation in the darkness, evoked a standing Ca(2+) gradient in tiger salamander photoreceptors with spatially-averaged intracellular Ca(2+) concentration within synaptic terminals of approximately 2 microM and lower (approximately 750 nM) intracellular calcium concentration in the ellipsoid. ⋯ L-type voltage-operated Ca(2+) channels and plasma membrane Ca(2+) ATPases were highly expressed in synaptic terminals with progressively lower expression levels in the cell body and ellipsoid. These results show photoreceptor Ca(2+) homeostasis is controlled in a region-specific manner by direct Ca(2+) entry and diffusion as well as Ca(2+) extrusion. Moreover, quantitative measurement of intracellular calcium concentration levels in different photoreceptor compartments indicates that the dynamic range of Ca(2+) signaling in photoreceptors is approximately 40-fold, from approximately 50 nM in the light to approximately 2 microM in darkness.
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The present study aimed to investigate whether tonic cutaneous pain exerts any effect on the cortical processing of nociceptive input and if this effect may involve only body parts in pain. Tonic cutaneous pain was obtained in nine healthy human subjects by infusion of a hypertonic saline (5%) in the s.c. tissue over the hypothenar muscles (10 ml/h for 20 min). Nociceptive cutaneous CO2 laser-evoked potentials were recorded after stimulation of the right hand dorsum, which was adjacent to the painful area, and the right perioral region, corresponding to the adjacent cortical sensory area. ⋯ Dipolar modeling showed that the dipolar source in the anterior cingulate cortex moved backward during saline infusion. This result suggests that cutaneous pain may modify the relative activities of the anterior and posterior anterior cingulate cortex parts, which are thought to be devoted to encode different aspects of pain sensation. No laser-evoked potential change was observed after stimulation of the right perioral region, suggesting that functional changes in the nociceptive system are selective for the painful regions and not for areas with cortical proximity.
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In vitro studies have demonstrated that prolonged N-methyl-D-aspartate receptor (NMDAR) blockade triggers a homeostatic up-regulation of NMDARs at synapses. Such upregulation can also be seen within 30 min in vivo in adult rats, implicating trafficking of reserve pools of NMDARs. Here, we evaluated the involvement of filamentous actin (F-actin), the major cytoskeletal component in spines, in this rapid in vivo homeostatic response, using biotinylated phalloidin as its probe. ⋯ However, the average postsynaptic density length was reduced by 25 nm among the fewer, drebrin A immuno-negative spines, indicating that drebrin A confers stability to synapse size. We propose that, in a homeostatic in vivo response, increases of drebrin A and F-actin within spines can enhance NMDAR trafficking by reducing cytoskeletal rigidity within the spine cytoplasm without changing the overt morphology of axo-spinous synapses. Alternatively or in addition, the cytoskeletal redistribution within spine cytoplasm may be triggered by the D-APV-induced, homeostatic up-regulation of NMDAR.
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This study evaluated the plastic changes of c-jun and c-fos in the right sixth lumbar dorsal root ganglion (L6 DRG), Rexed's lamina II in representative spinal segments L3, L5, and L6 and in the nucleus dorsalis (ND) at L3 segments after electro-acupuncture (EA) in cats subjected to removal of L1-L5 and L7-S2 DRG. Following dorsal root ganglionectomy, there was a significant increase in the density of c-jun immunoreactivity in the neurons and glia in spinal lamina II and in the ND; there was also marked elevation in the expression of c-fos in ND. In both cases there was no change in the c-jun and c-fos immunoreactivity in the DRG. ⋯ Following partial deafferentation, there was a significant increase in the protein level of both c-jun and c-fos in the dorsal horn, while, in both cases there was no change in c-jun and c-fos protein and mRNA in the DRG. After EA in the operated animals, both c-jun protein and its mRNA in the L6 DRG as well as the associated dorsal horn of L6 spinal segment were upregulated, but increased c-fos protein and its mRNA was observed only in the L6 DRG. These findings suggested that c-jun and c-fos might be related to the acupuncture promoted spinal cord plasticity as reported previously.