Neuroscience
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The projections of the substantia nigra pars compacta (SNc) to the reticular thalamic nucleus (RTn) were assessed by measuring dopamine content and counting tyrosine hydroxylase positive (TH (+)) cells in rats with unilateral lesions induced by 6-hydroxydopamine (6-OHDA), and by using a fluorescent tract-tracing technique in rats without lesions. Injection of 6-OHDA in the RTn reduced dopamine content and the number of TH (+) cells in the SNc by about 50%. Branching of SNc was suggested by the finding that 6-OHDA deposited in the RTn significantly reduced dopamine in the striatum and globus pallidus. ⋯ Other experiments showed that systemic injection of apomorphine or methamphetamine induced turning behavior in rats with local deposits of 6-OHDA in either the RTn or the studied basal ganglia nuclei. The extensive dopaminergic branching suggests that the abnormal motor behavior of rats with 6-OHDA deposits in the RTn may be caused by dopaminergic denervation of more than one structure. The fact that lesion of a single dopaminergic neuron can reduce dopamine transmission in more than one structure is probably important in generating the manifestations of Parkinson's disease.
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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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The molecular basis of high versus low frequency hearing loss and the differences in the sensitivity of outer hair cells depending on their cochlear localization are currently not understood. Here we demonstrate the existence of two different outer hair cell phenotypes along the cochlear axis. Outer hair cells in low frequency regions exhibit early sensitivity for loss of Ca(v)1.3 (alpha1 subunit 1.3 forming the class D L-type voltage-gated Ca(2+) channel), while high frequency regions display a progressive susceptibility for loss of the Ca(2+)-activated large conductance K(+) (BK) channel. ⋯ Otoferlin-expressing, Ca(v)1.3 deletion-sensitive outer hair cells in the low frequency range could be clearly separated from otoferlin-negative, BK deletion-sensitive outer hair cells in the high frequency range. In addition, BK deletion led to a higher noise vulnerability in low frequency regions, which are normally unaffected by the BK deletion alone, suggesting that BK currents are involved in survival mechanisms of outer hair cells under noise conditions. Our findings propose new mechanisms and candidate genes for explaining high and low frequency hearing loss.
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Comparative Study
Comparison of antinociceptive actions of standard analgesics in attenuating capsaicin and nerve-injury-induced mechanical hypersensitivity.
Intradermal capsaicin injection produces immediate spontaneous pain behaviors, and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic as a model potentially predictive of human neuropathic pain. Presently, we have characterized capsaicin-induced SMH in rats, and compared pharmacological actions of standard analgesics in this and two nerve injury models, the L5/L6 spinal nerve ligation (SNL) and sciatic nerve chronic constriction injury (CCI) models. Intraplantar capsaicin produced dose-related SMH (enhanced paw withdrawal response to von Frey monofilament stimulation at an area away from injection site) that lasted for over 4 h. ⋯ In contrast, celecoxib and ibuprofen showed weak effects in all three models. All standard analgesics generally had weak efficacy in attenuating capsaicin-induced immediate acute flinching behavior when administered before capsaicin. These results provide further support to the suggestions that distinct pharmacological mechanisms underlie capsaicin-induced acute nocifensive and SMH behaviors, and certain neuronal mechanisms underlying neuropathic pain states are also contributory to capsaicin-induced SMH.