Journal of neurophysiology
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The classic model of saccade generation assumes that the burst generator is driven by a motor-error signal, the difference between the actual eye position and the final "desired" eye position in the orbit. Here we evaluate objectively, using system identification techniques, the dynamic relationship between motor-error signals and primate inhibitory burst neuron (IBN) discharges (upstream analysis). The IBNs presented here are the same neurons whose downstream relationships were characterized during head-fixed saccades and head-free gaze shifts in our companion papers. ⋯ In the head-free monkey the ability of upstream models to predict IBN firing during head-free gaze shifts when gaze, eye, or head motor-error signals were model inputs was poor and similar to the upstream analysis of the head-fixed condition. We conclude that during saccades (head-fixed) or gaze shifts (head-free) the activity of both SLIBNs and LLIBNs is more closely linked to downstream events (i.e., the dynamics of ongoing movements) than to the coincident upstream motor-error signal. Furthermore, SLIBNs and LLIBNs do not differ in their characteristics; the latter are not, as is usually hypothesized, closer to a motor-error signal than the former.
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Long-lasting facilitations of spinal nociceptive reflexes resulting from temporal summation of nociceptive inputs have been described on many occasions in spinal, nonanesthetized rats. Because noxious inputs also trigger powerful descending inhibitory controls, we investigated this phenomenon in intact, halothane-anesthetized rats and compared our results with those obtained in other preparations. The effects of temporal summation of nociceptive inputs were found to be very much dependent on the type of preparation. ⋯ A similar long-lasting facilitation was seen in nonanesthetized, spinal rats. It is concluded that, in intact rats, an inhibitory mechanism counteracts the long-lasting increase of excitability of the flexor reflex seen in spinal animals after high-intensity, repetitive stimulation of C-fibers. It is suggested that supraspinally mediated inhibitions also participate in long term changes in spinal cord excitability after noxious stimulation.
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Several laboratories recently identified a 17 amino-acid peptide, termed "nociceptin" or "orphanin FQ (OFQ)", as the endogenous ligand for the LC132 (or "opioid receptor-like1") receptor. Taken together with the fact that the cellular effects of OFQ are to a large extent opioid-like, the close relationship between the LC132 receptor and known opioid receptors raised expectations that the behavioral effects of this peptide would resemble those of opioids. However studies of the role of OFQ in nociception have not provided a unified view. ⋯ Those of systemically administered morphine, which can produce its antinociceptive effects by acting at a number of CNS sites, were not blocked by RVM OFQ. Inasmuch as activation of -cells can account for the antinociceptive action of opioids within the RVM, these results demonstrate that, at least within the medulla, OFQ can exert a functional "antiopioid" effect by suppressing firing of this cell class. However to the extent that antinociceptive and pronociceptive outflows from various brain regions involved in both transmission and modulation of nociception are active under different conditions, focal application of OFQ in different regions could potentially produce either hypalgesia or hyperalgesia.
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We studied the effects of activation of the metabotropic glutamate receptors on intrinsic currents of magnocellular n urons of the supraoptic nucleus (SON) with whole cell patch-clamp and conventional intracellular recordings in coronal slices (400 micron) of the rat hypothalamus. Trans-(+/-)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 10-100 microM), a broad-spectrum metabotropic glutamate receptor agonist, evoked an inward current (18.7 +/- 3.45 pA) or a slow depolarization (7.35 +/- 4.73 mV) and a 10-30% decrease in whole cell conductance in approximately 50% of the magnocellular neurons recorded at resting membrane potential. The decrease in conductance and the inward current were caused largely by the attenuation of a resting potassium conductance because they were reduced by the replacement of intracellular potassium with an equimolar concentration of cesium or by the addition of potassium channel blockers to the extracellular medium. ⋯ A group II receptor agonist, 2S,1'S,2'S-2carboxycyclopropylglycine and a group III receptor agonist, (+)-2-amino-4-phosphonobutyric acid, had no effect on the resting or voltage-gated K+ currents, indicating that the reduction of K+ currents was mediated by group I receptors. About 80% of the SON cells that were labeled immunohistochemically for vasopressin responded to metabotropic glutamate receptor activation, whereas only 33% of labeled oxytocin cells responded, suggesting that metabotropic receptors are expressed preferentially in vasopressinergic neurons. These data indicate that activation of the group I metabotropic glutamate receptors leads to an increase in the postsynaptic excitability of magnocellular neurons by blocking resting K+ currents as well as by reducing voltage-gated and Ca2+-activated K+ currents.
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This paper is a combined experimental and modeling study of two fundamental questions surrounding the functional characteristics of Na+ currents in nodose sensory neurons. First, when distinctly different classes of Na+ currents are expressed in the same neuron, is there a significant difference in the intrinsic biological variability associated with the voltage- and time-dependent properties of these currents? Second, in what manner can such variability in functional properties impact the discharge characteristics of these neurons? Here, we recorded the whole cell Na+ currents in acutely dissociated rat nodose sensory neurons using the patch-clamp technique. Two general populations of neurons were observed. ⋯ The statistical profiles of the voltage- and time-dependent properties of these currents then were used as a physiological guide to adjust the relevant parameters of a mathematical model of nodose sensory neurons previously developed by our group (). Here, we show how the relative expression of TTX-S and TTX-R Na+ currents and the differences in their apparent biological variability can shape the regenerative discharge characteristics and action potential waveshapes of sensory neurons. We propose that the spectrum of variability robust reactivation characteristics of the TTX-R current are important determinants in establishing the heterogeneous stimulus-response characteristics often observed across the general population of C-type sensory neurons.