Neuroscience
-
Comparative Study
Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain.
Several experimental models of peripheral neuropathy show that a significant upregulation of spinal dynorphin A and its precursor peptide, prodynorphin, is a common consequence of nerve injury. A genetically modified mouse strain lacking prodynorphin does not exhibit sustained neuropathic pain after nerve injury, supporting a pronociceptive role of elevated levels of spinal dynorphin. A null mutation of the gamma isoform of protein kinase C (PKCgamma KO [knockout]), as well as an inbred mouse strain, 129S6, also does not manifest behavioral signs of neuropathic pain following peripheral nerve injury. ⋯ However, the PKCgamma KO mice and the 129S6 mice (which express PKCgamma) did not show abnormal pain after SNL; neither strain showed elevated levels of spinal dynorphin. The multiple phenotypic deficits in PKCgamma KO mice confound the interpretation of the proposed role of PKCgamma-expressing spinal neurons in neuropathic pain states. Additionally, the data show that the regulation of spinal dynorphin expression is a common critical feature of expression of neuropathic pain.
-
The cellular localization of the vesicular glutamate transporter 1, VGLUT1, was studied in the rat cerebral cortex with immunocytochemical techniques. VGLUT1 immunoreactivity (ir) was localized to punctate structures dispersed in the neuropil of all cortical layers as well as around the profile of somata and proximal dendritic segments of virtually all pyramidal neurons. ⋯ Perisomatic VGLUT1-positive terminals never formed synapses with the pyramidal cell bodies to which they were in apposition, but formed asymmetric synapses with adjacent neuropilar dendritic elements. The high probability of a close spatial relationship between glutamatergic and GABAergic terminals in perisomatic regions suggests that spilled-out glutamate may act on inhibitory axon terminals innervating the soma of cortical pyramidal neurons.
-
Comparative Study
Cellular localization of Shab and Shaw potassium channels in the lobster stomatogastric ganglion.
The motor pattern generated by the 14 neurons composing the pyloric circuit in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, is organized not only by the synaptic connections between neurons, but also by the characteristic intrinsic electrophysiological properties of the individual cells. These cellular properties result from the unique complement of ion channels that each cell expresses, and the distribution of those channels in the cell membranes. We have mapped the STG expression of shab and shaw, two genes in the Shaker superfamily of potassium channel genes that encode voltage-dependent, non-inactivating channels. ⋯ This supports Golowasch et al.'s [J Neurosci 19 (1999) RC33; Neural Comput 11 (1999) 1079] hypothesis that individual cells can have similar firing properties with varying compositions of ionic currents. Both antibodies stain the axons of the peripheral nerves as they enter foregut muscles. We conclude that both Shab and Shaw channels are appropriately localized to contribute to the noninactivating potassium current in the stomatogastric nervous system.
-
Comparative Study
Up-regulation of gamma-aminobutyric acid transporter I mediates ethanol sensitivity in mice.
Ethanol is among the most widely abused drugs in the world. Chronic ethanol consumption leads to ethanol tolerance and addiction, and impairs learning and memory. Na+/Cl- dependent GABA transporters play an important role in controlling the concentration of GABA in the synaptic cleft, and thus they control the intensity and duration of synaptic transmission of GABA. ⋯ These results suggest that GAT1 plays an important role in sensitivity to ethanol, and might be a therapeutic target for alcoholism prevention and treatment. Acute and chronic ethanol administration resulted in the increase of GABA transporter function. Use of GAT1 selective inhibitors and GAT1 overexpressing mice thus demonstrate that GAT1 should be an important protein mediating sensitivity to ethanol in mice.
-
Comparative Study
Role of 5-HT1B receptors in entrainment disorder of Otsuka Long Evans Tokushima fatty (OLETF) rats.
The role of 5-HT1A and 5-HT1B receptors in entrainment function was studied in Otsuka Long Evans Tokushima fatty (OLETF) rats and control Long Evans Tokushima Otsuka (LETO) rats. Light-induced (100 lux, 30 min) Fos expression in the suprachiasmatic nucleus was studied. Light-induced Fos expression was significantly decreased in OLETF rats compared to that in LETO rats. ⋯ Light-induced phase shifts of locomotor activity in OLETF rats were significantly smaller than those in LETO rats. The phase shifts were significantly increased by isamoltan (3 mg/kg, i.p.) in OLETF rats. These results suggest that 5-HT1B receptors are involved in the reduced entrainment function of OLETF rats.