The European journal of neuroscience
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Transient receptor potential vanilloid (TRPV)1 is a ligand-gated cation channel expressed by primary sensory neurons, including those in the dorsal root ganglia (DRG). TRPV1 plays an essential role in development of inflammatory thermal hyperalgesia after tissue injury and its expression in rat lumbar DRG is increased after hindpaw inflammation. However, the identity of factors mediating forepaw inflammatory hyperalgesia has remained elusive. ⋯ Paratracheal injection of short interfering RNA targeting TRPV1 blocked TRPV1 up-regulation in cervical DRG and abolished inflammation-mediated HPL reductions seen at 50 degrees C. However, thermal hyperalgesia previously established by inflammation was not reversed by short interfering RNA injection. These results indicate that: (i) enhanced TRPV1 expression in cervical DRG is closely associated with development of inflammatory thermal hyperalgesia in the forepaw after tissue injury and (ii) RNA interference targeting TRPV1 prevents inflammatory thermal hyperalgesia after forepaw injuries but does not ameliorate it when already established in a rat model of nociceptive pain representing upper limb injury in humans.
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The absence of a slice preparation with intact thalamocortical pathways has held back elucidation of the cellular and synaptic mechanisms by which thalamic signals are differentially transmitted to and processed in the anterior cingulate cortex (ACC). In this report we introduce an innovative mouse brain slice preparation in which it is possible to explore the electrophysiological properties of ACC neurons with intact long-distance inputs from medial thalamic (MT) nuclei by intracellular recordings; this MT-ACC neuronal pathway plays an integral role in information transmission. Biocytin-labeled fibers in a functional slice could be traced anterogradely or retrogradely from the MT via the reticular thalamic nuclei, striatum and corpus callosum to the cingulate cortical areas. ⋯ We observed enhanced paired-pulse facilitation and tetanic potentiation of thalamocingulate synapses, suggestive of input-specific ACC plasticity and selective processing of information relayed by thalamocingulate pathways. Furthermore, we observed differential responses of ACC neurons to thalamic burst stimulation, which underscores the importance of MT afferents in relaying sensory information to the ACC. This new slice preparation enables the contribution of MT-evoked ACC synaptic transmission to short-term plasticity in the neuronal circuitry underlying sensory information processing to be examined in detail.
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Comparative Study
Shedding light on circadian clock resetting by dark exposure: differential effects between diurnal and nocturnal rodents.
The master circadian clock in mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, is entrained by light and behavioural stimulation. In addition, the SCN can be reset by dark pulses in nocturnal rodents under constant light conditions. Here, the shifting effects of a dark pulse on the SCN clock were detailed at both a behavioural and molecular level in a nocturnal rodent (Syrian hamster), and were compared to those of a diurnal rodent (Arvicanthis ansorgei). ⋯ Despite that both hamsters and Arvicanthis showed dark-induced phase advances at circadian time-12, Per1 gene and its protein PER1 were downregulated in Arvicanthis but not in hamsters. Altogether these results show that dark resetting of the SCN is always associated with downregulation of Per1 and/or Per2 expression, and mostly occurs during resting. Thus, the circadian window of sensitivity to dark differs between nocturnal and diurnal rodents.
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Comparative Study
Neuromuscular paralysis and recovery in mice injected with botulinum neurotoxins A and C.
Botulinum neurotoxin type A (BoNT/A) is commonly used in human therapy. This treatment may induce immunoresistance and preliminary evaluation of other botulinum neurotoxin serotypes suggested botulinum neurotoxin type C (BoNT/C) to be a good alternative to BoNT/A. Here, we have further characterized the biological activities of BoNT/C using a variety of experimental approaches. ⋯ In BoNT/C-treated junctions, nerve terminal sprouting was prominent, indicating that the capacity to extend the field of innervation is not hampered by BoNT/C. BoNT/C induced a marked decrease in the frequency of miniature endplate potentials and in the amplitude of endplate potentials. 3,4-diaminopyridine reversed the effect of BoNT/C by increasing the amplitude of synchronized endplate potentials. The present study shows an extensive similarity in the biological activities of BoNT/A and BoNT/C, further supporting the suggestion that BoNT/C is a valid alternative to BoNT/A.
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During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans-striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. ⋯ Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine-deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.