Neuroscience
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There is general agreement that activation of the N-methyl-D-aspartate receptor is involved in thermal hyperalgesia. However, there is less agreement on the specific intracellular events subsequent to receptor activation and the involvement of other excitatory amino acid receptors in thermal hyperalgesia. In the present study, we found that the intrathecal administration of N-methyl-D-aspartate produced a dose- (1 fmol-1 pmol) and time-dependent thermal hyperalgesia. ⋯ Activation of AMPA, metabotropic or co-activation of AMPA and metabotropic glutamate receptors, at the doses tested, did not produce an acute thermal hyperalgesia. The thermal hyperalgesia produced by N-methyl-D-aspartate is mediated by activation of nitric oxide synthase and protein kinase C, but not by phospholipase C, phospholipase A2, cyclo-oxygenase or lipoxygenase. Collectively, the results are consistent with a role for spinal N-methyl-D-aspartate receptors, nitric oxide and protein kinase C in thermal hyperalgesia.
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Miniature endplate potentials were recorded from single frog muscle fibers before, during and after treatment with hypertonic saline (200-500 mM NaCl or Na gluconate added to frog saline). Miniature endplate potential amplitude distributions were plotted from small muscle fibers so that the modes and ratios of the skew-miniature endplate potential to bell-miniature endplate potential classes could be defined. Muscle fibers were voltage clamped with two electrodes to determine the input resistance before, during and after treatment. ⋯ The results presented here are completely different from those of Yu and Van der Kloot [(1991) J. Physiol. 433, 677-704] who reported that the bell-miniature endplate potential amplitude was increased two- to four-fold after hypertonic treatment. The wide range of results in the ratio of skew-miniature endplate potential to bell-miniature endplate potential classes is discussed in regards to the quantal hypothesis which is based on a single class of immutable amounts of transmitter; and, a hypothesis based on a dynamical process that meters transmitter in subunit amounts to control miniature endplate potential size and class during release.
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The functional organization of the cortico-nucleus accumbens-substantia nigra pars reticulata circuit was investigated in the rat using combined anatomical and electrophysiological approaches. The nucleus accumbens neurons which project to the substantia nigra pars reticulata are located in a circumscribed region of the core immediately adjacent and extending dorsally to the anterior commissure. As shown by retrograde and anterograde transports of wheatgerm agglutinin conjugated to horseradish peroxidase, the region of the nucleus accumbens related to the substantia nigra was found to receive bilateral inputs from restricted areas of the medial and lateral prefrontal cortex, i.e., prelimbic/medial orbital and dorsal agranular insular areas. ⋯ Furthermore, the present data also show that the stimulation of the medial prefrontal cortex results in a powerful inhibition of the tonic firing of the substantia nigra pars reticulata neurons. In conclusion, this study reveals the existence of a functional link between the prefrontal cortex (prelimbic/medial orbital and agranular insular areas) and the nucleus accumbens neurons which innervate the dorsomedial region of the substantia nigra pars reticulata. Since the dorsomedial region of substantia nigra pars reticulata is known to project to subfields of the mediodorsal and ventromedial thalamic nuclei related to the prefrontal cortex, the present data further demonstrate the existence of a prefrontal-nucleus accumbens-thalamo-cortical circuit involving the substantia nigra pars reticulata.
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We investigated the innervation of the caudal ventrolateral medulla by the midbrain periaqueductal gray in the rat using retrograde and anterograde tract-tracing. Iontophoretic injection of Fluoro-Gold or cholera toxin B subunit into the caudal ventrolateral medulla resulted in retrogradely labeled neurons in discrete regions of the periaqueductal gray. These labeled cells were observed throughout the rostrocaudal extent of the periaqueductal gray and were distributed (as percentage of total labeled cells) in its lateral (53-67%), ventrolateral (14-28%), ventromedial (7-16%) and dorsomedial aspects (7-10%). ⋯ Following iontophoretic injection into the periaqueductal gray, labeled fibers and terminals were observed throughout the rostrocaudal extent of the caudal ventrolateral medulla. Injections in the lateral and/or ventrolateral aspect of the periaqueductal gray yielded more anterograde labeling in the ipsilateral than the contralateral caudal ventrolateral medulla, while injections in the ventromedial aspect of the periaqueductal gray produced labeling preferentially in the contralateral caudal ventrolateral medulla. The present study indicates that specific regions of the periaqueductal gray project to the caudal ventrolateral medulla and may regulate cardiovascular and respiratory functions through these connections.