Progress in neurobiology
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Not later than two synapses after their arrival in the cerebellar cortex all excitatory afferent signals are subsequently transformed into inhibitory ones. Guaranteed by the exceedingly ordered and stereotyped synaptic arrangement of its cellular elements, the cerebellar cortex transmits this inhibitory result of cerebellar integration exclusively via Purkinje cells (PCs) in a precise temporal succession directly onto the target neurons of the deep cerebellar and vestibular nuclei. Thus the cerebellar cortex seems to produce a temporal pattern of inhibitory influence on these target neurons that modifies their excitatory action in such a way that an activation of muscle fibers occurs which progressively integrates the intended motion into the actual condition of the motoric inventory. ⋯ This is substantiated by stereotaxic removal of the remaining PC input, which eliminates the influence of the first mechanism and is able to induce the second strategy. As a consequence, motor performance improves considerably. In this review, results leading to the above conclusions are presented and links forged to human cerebellar diseases.
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Mammalian tissues contain at least two types of cannabinoid receptor, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB(2) receptors occur centrally and peripherally in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. ⋯ This review summarizes current knowledge about the ability of cannabinoids to produce antinociception in animal models of acute pain as well as about the ability of these drugs to suppress signs of tonic pain induced in animals by nerve damage or by the injection of an inflammatory agent. Particular attention is paid to the types of pain against which cannabinoids may be effective, the distribution pattern of cannabinoid receptors in central and peripheral pain pathways and the part that these receptors play in cannabinoid-induced antinociception. The possibility that antinociception can be mediated by cannabinoid receptors other than CB(1) and CB(2) receptors, for example CB(2)-like receptors, is also discussed as is the evidence firstly that one endogenous cannabinoid, anandamide, produces antinociception through mechanisms that differ from those of other types of cannabinoid, for example by acting on vanilloid receptors, and secondly that the endocannabinoid system has physiological and/or pathophysiological roles in the modulation of pain.
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The occurrence of neuronal death during development is well documented for some neuronal populations, such as motoneurones and dorsal root ganglion cells, whose connecting pathways are clearly defined. Cell survival is thought to be regulated largely by target and input connections, a process that serves to match the size of synaptically linked neuronal populations. Far less is known about interneurones. ⋯ There are many functional types of interneurones in the spinal cord that may differ in vulnerability to cell death, but it is concluded that for most spinal interneurones the traditional view of target regulation is unlikely. Instead it is proposed that developmental interneurone death in the spinal cord forms part of a plastic response to altered sensory activation rather than a size-matching exercise. There is also emerging evidence that interneurone death may play a more direct role in some neurodegenerative diseases than hitherto considered.
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Progress in neurobiology · Jun 2000
ReviewWind-up of spinal cord neurones and pain sensation: much ado about something?
Wind-up is a frequency-dependent increase in the excitability of spinal cord neurones, evoked by electrical stimulation of afferent C-fibres. Although it has been studied over the past thirty years, there are still uncertainties about its physiological meaning. Glutamate (NMDA) and tachykinin NK1 receptors are required to generate wind-up and therefore a positive modulation between these two receptor types has been suggested by some authors. ⋯ On the other hand, wind-up, central sensitisation and hyperalgesia are not the same phenomena, although they may share common properties. Wind-up can be an important tool to study the processing of nociceptive information in the spinal cord, and the central effects of drugs that modulate the nociceptive system. This paper reviews the physiological and pharmacological data on wind-up of spinal cord neurones, and the perceptual correlates of wind-up in human subjects, in the context of its possible relation to the triggering of hyperalgesic states, and also the multiple factors which contribute to the generation of wind-up.
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Near-infrared (IR) light easily penetrates biological tissue, and the information offered by in vivo spectroscopy of cerebral oxygenation is detailed and comes with a high temporal resolution. Near-IR light spectroscopy (NIRS) reflects cerebral oxygenation during arterial hypotension, hypoxic hypoxaemia and hypo- and hypercapnia. As determined by dual-wavelength NIRS, the cerebral O2 saturation integrates the arterial O2 content and the cerebral perfusion, and as established for skeletal muscle, NIRS obtains information on tissue oxygenation and metabolism beyond that obtained by venous blood sampling. ⋯ By NIRS, reduction of cytochrome oxidase is demonstrated during hypoxic hypoxaemia and head-up tilt-induced arterial hypotension, but the changes are small. In the clinical setting, NIRS offers useful information in patients with both systemic and local cerebral circulatory impairment, for example, during cranial trauma, surgery on the cerebral arteries, orthostasis and acute heart failure. Whereas mapping of the brain circulation is needed for jugular venous sampling to reflect either global or local oxygenation, the determination of cerebral oxygenation by NIRS has the advantage of localized monitoring of the cerebral cortex.