Physiological properties of raphe magnus neurons during sleep and waking.
Neurons in the medullary raphe magnus (RM) that are important in the descending modulation of nociceptive transmission are classified by their response to noxious tail heat as ON, OFF, or NEUTRAL cells. Experiments in anesthetized animals demonstrate that RM ON cells facilitate and OFF cells inhibit nociceptive transmission. Yet little is known of the physiology of these cells in the unanesthetized animal. The first aim of the present experiments was to determine whether cells with ON- and OFF-like responses to noxious heat exist in the unanesthetized rat. Second, to determine if RM cells have state-dependent discharge, the activity of RM neurons was recorded during waking and sleeping states. Noxious heat applied during waking and slow wave sleep excited one group of cells (ON-U) in unanesthetized rats. Other cells were inhibited by noxious heat (OFF-U) applied during waking and slow wave sleep states in unanesthetized rats. NEUTRAL-U cells did not respond to noxious thermal stimulation applied during either slow wave sleep or waking. ON-U and OFF-U cells were more likely to respond to noxious heat during slow wave sleep than during waking and were least likely to respond when the animal was eating or drinking. Although RM cells rarely respond to innocuous stimulation applied during anesthesia, ON-U and OFF-U cells were excited and inhibited, respectively, by innocuous somatosensory stimulation in the unanesthetized rat. The spontaneous activity of >90% of the RM neurons recorded in the unanesthetized rat was influenced by behavioral state. OFF-U cells discharged sporadically during waking but were continuously active during slow wave sleep. By contrast, ON-U and NEUTRAL-U cells discharged in bursts during waking and either ceased to discharge entirely or discharged at a low rate during slow wave sleep. We suggest that OFF cell discharge functions to suppress pain-evoked reactions during sleep, whereas ON cell discharge facilitates pain-evoked responses during waking. (+info)
Effect of psychotropic drugs on caudate spindle in cats.
To ascertain whether neuroleptics act on the caudate nucleus itself, the effects of these compounds as well as other centrally acting drugs were examined in relation to caudate spindle and EEG arousal responses (sciatic nerve stimulation) in gallamine-immobilized cats. Haloperidol and chlorpromazine enhanced the caudate spindle at a dose which had no effect on the EEG arousal response. On the other hand, clozapine and a higher dose of chlorpromazine enhanced the caudate spindle, but depressed the arousal response. High frequency stimulation of the sciatic nerve suppressed the caudate spindle. Pentobarbital, biperiden and diazepam, while depressing the arousal response, caused an enhancement of the caudate spindle. Imipramine at a low dose had no effect on either response, whereas at a high dose this drug enhanced the caudate spindle with concomitant depression of the arousal response. From these results, it may be concluded that the enhancing action on the caudate spindle induced by haloperidol and a low dose of chlorpromazine is due to an increase in susceptibility of the caudate nucleus itself. In addition, it is suggested that depression of the activating system is involved in an appearance of the caudate spindle. (+info)
Arousal from sleep shortens sympathetic burst latency in humans.
1. Bursts of sympathetic activity in muscle nerves are phase-locked to the cardiac cycle by the sinoaortic baroreflexes. Acoustic arousal from non-rapid eye movement (NREM) sleep reduces the normally invariant interval between the R-wave of the electrocardiogram (ECG) and the peak of the corresponding sympathetic burst; however, the effects of other forms of sleep disruption (i.e. spontaneous arousals and apnoea-induced arousals) on this temporal relationship are unknown. 2. We simultaneously recorded muscle sympathetic nerve activity in the peroneal nerve (intraneural electrodes) and the ECG (surface electrodes) in seven healthy humans and three patients with sleep apnoea syndrome during NREM sleep. 3. In seven subjects, burst latencies were shortened subsequent to spontaneous K complexes (1.297 +/- 0.024 s, mean +/- s. e.m.) and spontaneous arousals (1.268 +/- 0.044 s) compared with latencies during periods of stable NREM sleep (1.369 +/- 0.023 s). In six subjects who demonstrated spontaneous apnoeas during sleep, apnoea per se did not alter burst latency relative to sleep with stable electroencephalogram (EEG) and breathing (1.313 +/- 0.038 vs. 1.342 +/- 0.026 s); however, following apnoea-induced EEG perturbations, burst latencies were reduced (1.214 +/- 0.034 s). 4. Arousal-induced reduction in sympathetic burst latency may reflect a temporary diminution of baroreflex buffering of sympathetic outflow. If so, the magnitude of arterial pressure perturbations during sleep (e.g. those caused by sleep disordered breathing and periodic leg movements) may be augmented by arousal. (+info)
Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression.
The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome. (+info)
Intrapreoptic microinjection of GHRH or its antagonist alters sleep in rats.
Previous reports indicate that growth hormone-releasing hormone (GHRH) is involved in sleep regulation. The site of action mediating the nonrapid eye movement sleep (NREMS)-promoting effects of GHRH is not known, but it is independent from the pituitary. GHRH (0.001, 0. 01, and 0.1 nmol/kg) or a competitive antagonist of GHRH (0.003, 0.3, and 14 nmol/kg) was microinjected into the preoptic area, and the sleep-wake activity was recorded for 23 hr after injection in rats. GHRH elicited dose-dependent increases in the duration and in the intensity of NREMS compared with that in control records after intrapreoptic injection of physiological saline. The antagonist decreased the duration and intensity of NREMS and prolonged sleep latency. Consistent alterations in rapid eye movement sleep (REMS) and in brain temperature were not found. The GHRH antagonist also attenuated the enhancements in NREMS elicited by 3 hr of sleep deprivation. Histological verification of the injection sites showed that the majority of the effective injections were in the preoptic area and the diagonal band of Broca. The results indicate that the preoptic area mediates the sleep-promoting activity of GHRH. (+info)
EEG surveillance as a means of extending operability in high risk carotid endarterectomy.
Some patients who have transient ischemic attacks are denied operation because severe occlusive lesions in other extra-cranial arteries may be inappropriately interpreted as constituting an unacceptable surgical risk, or because the lesion is so distal as to make its removal hazardous. Failure of endarterectomy is usually due to incomplete removal of the lesion or to thrombosis upon the frayed intima. Such lesions require excellent visualization and meticulous surgical technique -- not always possible with a shunt. Among 130 consecutive carotid endarterectomies performed under general anesthesia, EEG changes consistent with cerebral ischemia appeared in only nine (7%). These patients required a shunt. In 11 patients normal EEG tracings were obtained during endarterectomy despite contralateral carotid occlusion. None of these patients had a neurological deficit. Continuous EEG monitoring is a reliable method of detecting changes in cerebral perfusion, permits a more meticulous endarterectomy in high-lying lesions without a shunt, and extends operability in high risk patients. Angiographical findings may be an unreliable predictor concerning risk of endarterectomy. (+info)
Intensive care management of stroke patients.
Two hundred eighty patients were admitted to an intensive care stroke unit over a one-year period. Subsequent investigation indicated that only 199 of these patients actually had cerebral ischemic or hemorrhagic lesions, 10 had other cerebrovascular lesions, and the remaining 71 patients had unrelated diseases, predominantly seizures. Detailed analysis of 103 stroke patients revealed an overall incidence of 59% hypertension, and 72% had hypertensive, ischemic or valvular heart disease. Fifty percent of the patients had various cardiac arrhythmias, some of which were responsible for the acute cerebrovascular lesion. Fourteen patients died during the acute phase, 11 from apparently irreversible cerebral selling, mainly due to cerebral hemorrhage. Secondary complications such as pneumonia, pulmonary embolism, pressure sores and urinary infection were almost nonexistent, but beneficial effects on the primary cerebral lesions were more difficult to demonstrate. (+info)
Subcortical arteriosclerotic encephalopathy (Binswanger's disease). A vascular etiology of dementia.
A 51-yearold man with moderate intermittent hypertension had a rapidly progressive, profound dementia in the absence of significant localizing neurological signs. Postmortem examination disclosed the vascular alterations and diffuse white matter degeneration which characterize subcortical arteriosclerotic encephalopathy (SAE) or Binswanger's disease. The case underscores the need to consider vascular disease as an etiology of dementia -- even in the absence of focal neurological deficit. (+info)