The Journal of neuroscience : the official journal of the Society for Neuroscience
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Neuronal activity was recorded in the dorsal accessory inferior olive in infant rats during classical conditioning of the eye-blink response. The percentage and amplitude of eye-blink conditioned responses (CRs) increased as a function of age. ⋯ The results indicate that the development of the conditioned eye-blink response may depend on dynamic interactions between multiple developmental processes within the eye-blink circuitry. Differences in the functional maturity of olivo-cerebellar pathways may limit the induction of plasticity in the cerebellum and thereby limit the development of eye-blink conditioned responses.
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The subthalamic nucleus (STN) is a key nucleus in the basal ganglia motor circuit that provides the major glutamatergic excitatory input to the basal ganglia output nuclei. The STN plays an important role in normal motor function, as well as in pathological conditions such as Parkinson's disease (PD) and related disorders. Development of a complete understanding of the roles of the STN in motor control and the pathophysiological changes in STN that underlie PD will require a detailed understanding of the mechanisms involved in regulation of excitability of STN neurons. ⋯ Interestingly, pharmacological studies suggest that each of the mGluR-mediated effects is attributable to activation of mGluR5, not mGluR1, despite the presence of both subtypes in STN neurons. These results suggest that mGluR5 may play an important role in the net excitatory drive to the STN from glutamatergic afferents. Furthermore, these studies raise the exciting possibility that selective ligands for mGluR5 may provide a novel approach for the treatment of a variety of movement disorders that involve changes in STN activity.
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Antagonism of the melanocortin system reduces cold and mechanical allodynia in mononeuropathic rats.
The presence of both pro-opiomelanocortin-derived peptides and melanocortin (MC) receptors in nociception-associated areas in the spinal cord suggests that, at the spinal level, the MC system might be involved in nociceptive transmission. In the present study, we demonstrate that a chronic constriction injury (CCI) to the rat sciatic nerve, a lesion that produces neuropathic pain, results in changes in the spinal cord MC system, as shown by an increased binding of (125)I-NDP-MSH to the dorsal horn. Furthermore, we investigated whether intrathecal administration (in the cisterna magna) of selective MC receptor ligands can affect the mechanical and cold allodynia associated with the CCI. ⋯ No antinociceptive action was observed after administration of the selective MC3 receptor agonist Nle-gamma-MSH. Together, our data suggest that the spinal cord MC system is involved in neuropathic pain and that the effects of MC receptor ligands on the responses to painful stimuli are exerted through the MC4 receptor. In conclusion, antagonism of the spinal melanocortin system might provide a new approach in the treatment of neuropathic pain.
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We have recently disrupted Slc12a2, the gene encoding the secretory Na-K-2Cl cotransporter in mice (NKCC1) (Delpire et al., 1999). Gramicidin perforated-patch and whole-cell recordings were performed to study GABA-induced currents in dorsal root ganglion (DRG) neurons isolated from wild-type and homozygote NKCC1 knock-out mice. In wild-type DRG neurons, strong GABA-evoked inward current was observed at the resting membrane potential, suggesting active accumulation of Cl(-) in these cells. ⋯ Application of bumetanide induced a positive shift of E(GABA), suggesting the presence of an outward Cl(-) transport mechanism. In agreement with an absence of GABA depolarization in DRG neurons, behavioral analysis revealed significant alterations in locomotion and pain perception in the knock-out mouse. Our results clearly demonstrate that the Na-K-2Cl cotransporter is responsible for [Cl(-)](i) accumulation in DRG neurons and that via regulation of intracellular Cl(-), the Na-K-2Cl cotransporter participates in the modulation of GABA neurotransmission and sensory perception.
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Although behavioral studies suggest that pain distress may alter the perception of somatic stimulation, neural correlates underlying such alteration remain to be clarified. The present study was aimed to test the hypothesis that expectation of pain might amplify brain responses to somatosensory stimulation in the anterior cingulate cortex (ACC) and the region including parietal operculum and posterior insula (PO/PI), both of which may play roles in regulating pain-dependent behavior. We compared brain responses with and subjective evaluation of physically identical nonpainful warm stimuli between two psychologically different contexts: one linked with pain expectation by presenting the nonpainful stimuli randomly intermixed with painful stimuli and the other without. ⋯ The enhanced responses were revealed as a higher intensity of signal change in ACC and larger volume of activated voxels in PO/PI. Behavioral measurements demonstrated that expectation of painful stimulus amplified perceived unpleasantness of innocuous stimulus. From these findings, it is suggested that ACC and PO/PI are involved in modulation of affective aspect of sensory perception by the uncertain expectation of painful stimulus.