The Journal of neuroscience : the official journal of the Society for Neuroscience
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Propofol (2,6 di-isopropylphenol) is an alkyphenol recently introduced for use as a general anesthetic. The modulation of GABAA receptor activation and desensitization by propofol was studied using a rapid perfusion system and whole-cell voltage-clamp recordings from mouse hippocampal neurons. The effects of concentrations of propofol used clinically on single-channel and synaptic currents were also examined. ⋯ A sequential model, based on a previous scheme of GABA receptor gating (Weiss and Magelby, 1989), is presented to summarize propofol's actions on GABAA receptor function. We show through simulation that the model reliably reproduced the whole-cell tracings. Our results indicate that propofol's neurodepressive actions will be associated with enhancement of inhibitory synaptic transmission.
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Comparative Study
Topographic organization of respiratory responses to glutamate microstimulation of the parabrachial nucleus in the rat.
The parabrachial complex, also known as the pneumotaxic center or pontine respiratory group, has long been recognized as an important participant in respiratory control. One line of evidence supporting this idea is the demonstration of changes in breathing pattern following injection of neuroactive substances into or near the parabrachial complex. However, it is not yet known exactly which cell groups and projections mediate those responses. ⋯ Scattered neurons in these sites were retrogradely labeled from the ventral but not the dorsal respiratory group. These results indicate that there are anatomically and functionally distinct cell populations in and near the parabrachial complex that, when chemically stimulated, can produce specific and sometimes opposing effects on respiration. The predominant effect of lateral parabrachial stimulation is respiratory facilitation, while inhibitory effects are elicited by trigeminal injections of glutamate.
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By using in situ hybridization histochemistry and immunohistochemistry, neuropeptide Y (NPY) and NPY (Y1) receptor mRNA as well as NPY-like immunoreactivity were examined in the lumbar spinal cord (L4-L5) and in dorsal root ganglia (DRG, L5) in rats injected with complete Freund's adjuvant (CFA) into the hindpaw. A rapid and marked increase in NPY mRNA expression was observed in ipsilateral dorsal horn neurons 6 hr after inoculation as compared to the contralateral side. This was mainly found in the medial part of spinal lamina II. ⋯ Numerous Y1 mRNA-positive, small neuron profiles were found bilaterally in the DRGs in CFA-treated rats. CFA evoked a 34% increase in the number of Y1 mRNA-positive neurons in ipsilateral DRGs as compared to contralateral DRGs. The distinct upregulation of NPY and NPY (Y1) receptor in response to peripheral inflammation suggests an involvement of NPY in the response to inflammation and in nociception.
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Rats receiving unilateral dopamine (DA) depletions have bilateral deficits in using the forelimbs for skilled reaching. These impairments were investigated using end-point, video, and kinematic measures. Control rats and groups of rats with > 98% unilateral depletions (confirmed by tissue, apomorphine, and amphetamine assay), produced by 6-hydroxydopamine (6-OHDA) injected into the nigrostriatal bundle, were tested for 100 d on two reaching tasks. ⋯ The group using their bad limb initiated reaching from a base of support distributed on the ipsilateral-to-lesion limbs, while the group using their good limb initiated reaching from a base of support centered on the ipsilateral rear limb. The impairments in making voluntary movements and postural adjustments with the bad limbs and the behavioral changes introduced by the compensatory dependency on good limbs account for the bilateral deficits in skilled movements. The results show that DA is required for skilled movements and postural adjustments and demonstrate that behavioral compensation can contribute to recovery.
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Severe tissue acidosis has been viewed traditionally as a damaging component of cerebral hypoxia. However, a neuroprotective action of low pH during hypoxia has been described in primary neuronal cultures. To identify and characterize this effect in mature brain tissue, adult rat hippocampal slices were made hypoxic after adjusting pHo with HCl or NaOH. ⋯ For each of these parameters, mild alkalinity (bath pH = 7.7) had the opposite effect. Acid treatment did not affect the decrease in [Ca2+]o during HSD but accelerated its recovery after reoxygenation. These results suggest that mild acidosis may limit hypoxic neuronal injury in vitro by delaying HSD onset and by additional mechanisms unrelated to the degree of calcium influx during neuronal depolarization.