Neuroscience
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Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study. We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. ⋯ Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (>50%), the majority of which demonstrated a prominent LTS and may correspond to pontine-geniculate-occipital burst neurons. Some or all carbachol-excited neurons are presumably REM-on neurons.
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Atypical antipsychotic drugs, such as olanzapine, have been reported to activate the locus coeruleus (LC) and lead to acute expression of the Fos-like immediate early gene (IEG) protein in the LC and medial prefrontal cortex (mPFC). Stimuli that activate the LC have been reported to increase expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. However, the effects of chronic treatment with olanzapine on IEG expression and the dose-dependence of the effects of olanzapine on IEG and TH expression are not known. ⋯ At all doses, there were rapid and sustained increases in TH immunoreactivity in the LC, but only delayed increases in the mPFC. These data indicate that olanzapine has rapid effects on IEG in the LC and mPFC, many of which are sustained through four weeks of treatment. Further, these data indicate that the delayed increase in TH expression in the mPFC parallels, and may play an important role in, the increased efficacy of olanzapine that emerges over time in humans.
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Two vestibular pathways converge at the uvula-nodulus to modulate the discharge of Purkinje cell complex and simple spikes (CSs and SSs). In the mouse, vestibular primary afferent mossy fibers originate from each of the end organs of the ipsilateral labyrinth and terminate in the granule cell layers of folia 9c-10. Vestibular climbing fiber projections originate from the contralateral beta-nucleus and dorsomedial cell column (dmcc) and terminate directly on Purkinje cells. ⋯ Purkinje cells with optimal planes in the anterior quadrant of the ipsilateral hemi-field were located in a lateral zone. The CS-associated pause in SSs establishes a vector-specific SS output. The amplitude of SS modulation may depend on parallel fiber-mediated signals to Purkinje cells as well as on the state of cerebellar interneurons.
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Spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain. However, in recent studies conflicting results regarding the effect of SCS were noted in a selected group of patients suffering from complex regional pain syndrome and mechanical allodynia. In the present study we investigated the pain relieving effect of SCS in a rat experimental model of neuropathic pain as related to the severity of mechanical allodynia. ⋯ Our data demonstrate a differential effect of SCS related to the severity of the mechanical allodynia. SCS leads to a faster and better pain relief in mildly allodynic rats as compared with the more severely allodynic rats. Thus, we suggest that the selection and subdivision of patient groups similar to those defined in our experimental setting (mild, moderate and severe allodynic) may provide better pre-treatment prediction of possible therapeutic benefits of SCS.
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Recent data support an important role for calcitonin gene-related peptide (CGRP) in deep tissue nociceptive processing. Using real-time reverse transcriptase polymerase chain reaction (RT-PCR), radioimmunoassay, immunohistochemistry and behavioral testing, we studied the early time course of CGRP mRNA and protein expression as well as nociceptive behavior following muscle inflammation. A rapid and significant increase in CGRP mRNA occurred in the mandibular division (V3) of the ipsilateral trigeminal ganglion at 30 minutes, 4 and 24 h after the injection of complete Freund's adjuvant as an inflammatory agent into rat masseter muscle. ⋯ Behavioral testing showed a reduction in head withdrawal thresholds bilaterally from 30 min through 24 h following muscle inflammation. Thus upregulation of CGRP mRNA and iCGRP levels are temporally related to the development of inflammation and lowered pain thresholds. The present data support the hypothesis that CGRP is upregulated during deep tissue inflammation and suggest that gene transcription is involved in this upregulation.