Neuroscience
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Comparative Study
A peripheral cannabinoid mechanism suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.
The present studies were conducted to test the hypothesis that systemically inactive doses of cannabinoids suppress inflammation-evoked neuronal activity in vivo via a peripheral mechanism. We examined peripheral cannabinoid modulation of spinal Fos protein expression, a marker of neuronal activity, in a rat model of inflammation. Rats received unilateral intraplantar injections of carrageenan (3%). ⋯ The suppressive effects of WIN55,212-2 (30 microg intraplantarly) on carrageenan-evoked Fos protein expression and pain behavior were blocked by local administration of either the CB(2) antagonist SR144528 (30 microg intraplantarly) or the CB(1) antagonist SR141716A (100 microg intraplantarly). WIN55,212-3, the enantiomer of the active compound, also failed to suppress carrageenan-evoked Fos protein expression. These data provide direct evidence that a peripheral cannabinoid mechanism suppresses the development of inflammation-evoked neuronal activity at the level of the spinal dorsal horn and implicate a role for CB(2) and CB(1) in peripheral cannabinoid modulation of inflammatory nociception.
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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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Comparative Study
Neuregulin-1beta modulates in vivo entorhinal-hippocampal synaptic transmission in adult rats.
Neuregulin-1 (NRG-1) proteins and their erbB receptors are essential for neuronal development during embryogenesis and may contribute importantly to neuronal function in the adult brain. This study tests the hypothesis that NRG-1beta acts as a modulator of synaptic activity in the adult brain, specifically at hippocampal formation synapses. Adult, male Sprague-Dawley rats were anesthetized and a recording electrode with an attached stainless steel microinjector was stereotaxically positioned to record field potentials (fEPSP) in either the dentate gyrus or the cornu ammonis (CA) 1 field of the hippocampus. ⋯ In contrast to its effect at the entorhinal-dentate synapse, NRG-1beta (100 nM) depressed, and PD158780 potentiated entorhinal-CA1 synaptic transmission. Thus, in adult rats NRG-1beta potentiates transmission at the entorhinal-dentate synapse but suppresses transmission at the entorhinal-CA1 synapse. These observations indicate that NRG-1 is not only a developmental growth factor, but also modifies synaptic transmission in adult rat brain.
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Comparative Study
In vitro reconstitution of signal transmission from a hair cell to the growth cone of a chick vestibular ganglion cell.
Signal transmission from a chick hair cell to the growth cone of a vestibular ganglion cell was examined by placing an acutely dissociated hair cell on the growth cone of a cultured vestibular ganglion cell. Electrical stimuli were applied to the hair cell while monitoring the intracellular Ca(2+) concentration ([Ca(2+)](i)) at the growth cone or recording whole-cell currents from the vestibular ganglion cell. Electrical stimulation of the hair cell induced [Ca(2+)](i) increases at the growth cone and inward currents in the vestibular ganglion cell. ⋯ Glutamate (100 nM-300 microM) applied to the vestibular ganglion cell by the Y-tube method induced inward currents which were also antagonized by CNQX, but not by APV. These results indicate that the electrical stimulation of a hair cell induced glutamate or glutamate like agent release from the hair cell, which activated non-N-methyl-D-aspartate receptors at the growth cone of the vestibular ganglion cell, followed by action potentials and [Ca(2+)](i) elevation in the vestibular ganglion cell. This is the first demonstration of in vitro reconstitution of functional signal transmission from a hair cell to a vestibular ganglion cell.
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Although the major routes of dopamine metabolism seem to be established, at least in terminal regions such as the striatum, it is important to search for previously unknown metabolites and to investigate the relevance of previously suggested minor alternative pathways. An urgent issue is to verify and quantify the transformation of dopamine to putative toxic species, another is to further explore metabolism of dopamine located in cell bodies/dendrites, e.g. in the substantia nigra. We have developed a new method in order to widen the search for alternative metabolites of dopamine. ⋯ The method was used to evaluate the possibility that cytochrome P450 2E1 is involved in the metabolism of dopamine in the substantia nigra. Significant changes in the radioactivity pattern were induced by inhibition of the enzyme but conclusions about whether cytochrome P450 2E1 is involved in the metabolism of dopamine or not requires further studies. The method can be used to study the metabolism of dopamine and can be extended, by using other radiolabelled precursors, also to evaluate metabolism of other transmitters, e.g. serotonin.