Neuroscience
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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.
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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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In rats, cannabinoids inhibit behavioral responses to noxious stimulation with a potency and efficacy similar to that of morphine. However, because cannabinoids depress motor function, it has not been possible to state beyond any doubt that these effects were related to a dampening of noxious sensory input. Therefore, c-fos immunocytochemistry was used to explore the possibility that cannabinoids reduce behavioral responses to noxious stimuli by decreasing spinal processing of nociceptive inputs. ⋯ Decreased expression of c-fos also occurred in the ventral horn. The specificity of this effect and its probable mediation by cannabinoid receptors are suggested by three findings: (i) the suppression by the drug of both behavioral and immunocytochemical responses to pain was dose-dependent; (ii) neither the behavioral nor the immunocytochemical response to the noxious stimulus was significantly affected by the receptor-inactive enantiomer of the agonist; (iii) animals rendered tolerant to cannabinoids by repeated injections of the agonist showed reduced responses to the drug. These findings suggest that cannabinoids inhibit the spinal processing of nociceptive stimuli and support the notion that endogenous cannabinoids may act naturally to modify pain trnasmission within the central nervous system.
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While serotonin has been shown to play an important role in peripheral pain mechanisms, the specific subtypes of receptors involved and their differential distribution between the sensory and sympathetic nervous system remains poorly understood. In this study, the presence of messenger RNA for rat serotonin receptor subtypes in peripheral sensory and sympathetic ganglia was detected using the method of polymerase chain reaction. Lumbar dorsal root ganglia, superior cervical sympathetic ganglia and lumbar sympathetic ganglia were excised from anesthetized Sprague-Dawley rats. ⋯ Lumbar sympathetic ganglia displayed banding identical to the superior cervical ganglia with the exception of the 5-HT6 receptor which was not detected in the lumbar sympathetic ganglia. The polymerase chain reaction product from each positively-detected receptor subtype was subcloned and sequenced and found to correspond to published complementary DNA sequences. Findings from this study may direct further efforts to determine the role of 5-hydroxytryptamine receptors in the peripheral nervous system.