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Biomedical subjects

M Mirmiran

Publications and source records attributed to M Mirmiran.

At least 73 records · Page 4Linked to original sources

Event related potentials recorded from rats performing a reaction-time task.

We recorded evoked potentials during performance of a reaction-time task, in which rats had to release a lever quickly in response to either a visual or an auditory stimulus for a food reward. We found two distinct peaks in their cortical evoked potentials. The first peak appeared at a fixed time after the stimulus, irrespective of the time it took the rat to release the lever. Its amplitude decreased with increasing reaction time. The second peak's latency was always longer when the rat took more time to release the lever, but its amplitude did not change. We believe that the first peak's amplitude is determined by the rat's "attention" to the stimulus, whereas the second peak's latency is related to the rat's "intention" to release the lever.

Animals↗

A simple method for recording and analysing circadian rhythms in man.

We describe a method for recording human rest-activity and body temperature. A small automatic cordless electronic device has been developed in order to record circadian rhythmicity of rest-activity for a period of one week. A comparable device connected to a small temperature transducer by means of a flexible probe was designed to register body temperature. These devices can register human circadian rhythms without interfering with their normal daily activity.

Autoanalysis↗

Effects of enhanced cerebrospinal fluid levels of vasopressin, vasopressin antagonist or vasoactive intestinal polypeptide on circadian sleep-wake rhythm in the rat.

Several endogenous peptides have been implicated in the regulation of sleep and wakefulness. The present study was carried out in order to determine whether the light-dark rhythm of vasopressin (VP) in the cerebrospinal fluid (CSF) had functional significance in relaying information from the circadian pacemaker, i.e. the suprachiasmatic nuclei (which synthesize VP as well as vasoactive intestinal polypeptide (VIP], to the centra regulating sleep. After constant delivery of VP in the CSF via an Accurel/collodion implant in the lateral ventricle, the VP CSF level was raised from 20-35 pg/ml to ca. 265 pg/ml whereby a VP rhythm in the CSF could no longer be detected. Under these conditions VP was found to increase the arousal state of the rat in the dark period, which resulted in a higher amplitude of the circadian sleep-wake rhythm. Application of the VP antagonist d(CH2)5[Tyr(Me)2]VP partly had opposite effects. A similar approach with central application of VIP resulted in an increase in rapid eye movement and quiet sleep but did not affect the amplitude of the circadian rhythm. It was concluded that although peptide levels in the CSF may show clear temporal variations with the light-dark cycle, this rhythmicity is not causally related to the circadian aspect of sleep-wakefulness. However, both VP and VIP contribute to the regulation of the amount of time spent in sleep and wakefulness and the level of VP in the CSF is correlated with the amplitude of the rhythm.

Animals↗

Age-related changes in circadian sleep-wakefulness rhythms in male rats isolated from time cues.

Sleep-wakefulness rhythms were recorded for at least 5 consecutive days in young adult (n = 6; 5-8 months) and old (n = 4; 30-32 months) rats. During the continuous recordings the rats were maintained in isolated cabins under constant temperature and constant dim, red light. The period length and amplitude of the free-running circadian rhythms of wakefulness (W), slow wave sleep (SWS) and desynchronized sleep (DS) were estimated by means of a cosine curve fitting program. Age-related amplitude differences were absent under the constant recording conditions. The circadian period of the W- and DS-rhythms, however, was significantly shorter in the old rats. These results are consistent with the notion that circadian organization is changed in old age.

Aging↗

Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging.

The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be the endogenous clock of the mammalian brain, regulating circadian rhythmicity of a great number of physiological and behavioural parameters. Numerous studies have shown that the circadian organization in the rat is progressively disturbed in senescence. However, a recent study by Peng et al.17 using conventionally stained material, revealed no decrease in overall SCN cell number of senescent rats. Their results have now been confirmed in this study. In addition, an increase in SCN volume (P = 0.02) and nucleus diameter (P = 0.001) and an overall decrease in cell density (P = 0.006) was observed. All these parameters seem to confirm the absence of a general degeneration in the senescent SCN. However, the major aim of the present study was to determine whether a well-defined population of neurons, i.e. the vasopressinergic (AVP) cells of the SCN, shows changes with aging. Immunocytochemical staining with antivasopressin and morphometry revealed a decrease of 31% (P = 0.007) in the number of these SCN neurons, whereas the remaining vasopressin cells became larger (P = 0.001). There were no statistical significant differences between rats housed in standard cages and those housed in an enriched environment in either age group, but the groups were relative small. Changes in either the number or stainability of SCN vasopressin neurons may be a morphological correlate of changed circadian rhythms in senescence.

Aging↗

Effect of housing in an enriched environment on the size of the cerebral cortex in young and old rats.

To assess whether or not environmental changes may continue to affect measures relating to cortical size, the size of the cerebral cortex of young adult (7 to 8 months) and old (32 to 33 months) "standard" and "enriched" rats were compared. Enriched rats were housed in large cages during 10 weeks and had access to many different objects; age-matched controls remained in standard laboratory cages. Effects on the cerebral cortex were small; a significant increase in cortical thickness at one, albeit different, site in both age groups was observed. Significant correlations were not present between environmentally induced changes in sleep parameters (recorded in the same rats prior to the present experiment) and the small change in cortical size. The results do, however, support the hypothesis that a certain amount of plasticity of the cerebral cortex is preserved in old age.

Age Factors↗

Central noradrenaline depletion during development and its effect on behaviour.

Although early depletion of noradrenaline is known to affect the morphological development of various structures in the brain, it is not clear what implications this has for adult behaviour. In the present study, 6-hydroxydopamine (6OHDA) was injected into the lateral ventricles of 12 day old rats, permanently destroying most of the noradrenergic innervation of the spinal cord and of all the brain areas examined except for the pons/medulla, and reducing the dopamine content of the cerebral cortex considerably. The noradrenaline content of the heart, as well as general developmental parameters such as food intake and body weight, were unaffected. Despite the extensive noradrenaline depletion during development, these rats' spatial memory--as determined in a radial maze task--was no worse than that of controls. In a lever-pressing task the 6OHDA treated rats made no more errors than did controls, but performed more slowly. The results indicate that at least some aspects of learning, memory and sensory-motor ability can develop normally when the noradrenergic innervation of the brain is largely destroyed.

Animals↗

No increase in reaction-time after lesion of the dorsal noradrenergic bundle.

In this study we examined whether lesions of rats' dorsal noradrenergic bundles affect their reaction times to temporally unpredictable stimuli. Injection of 6-hydroxydopamine into rats' dorsal bundles drastically reduced the noradrenaline content of their cerebral cortex. Nevertheless, 6OHDA treated rats could still react as quickly as controls. Moreover, the treatment did not affect the efficiency with which rats performed the task, even when they were forced to respond very quickly.

Animals↗

Effect of noradrenergic denervation on task-related visual evoked potentials in rats.

The present study examines whether destruction of the noradrenergic innervation of the forebrain interferes with the processing of sensory information in a manner that results in impaired selective attention. Electro-cortical responses to task-relevant and irrelevant stimuli were found to be sensitive indicators of the rat's attention to the stimuli. The amplitude of the response to the task-relevant stimulus increased as the rat's performance improved. The response to irrelevant flashes of light depended on the predictability of the flashes and on the rat's level of arousal. Noradrenergic denervation (with the selective neurotoxin DSP4) did not affect either the behavioural response to a visual stimulus which the rat had been trained to respond to for a food reward, or the late positive potential evoked by this stimulus. Neither did it affect the response to continuous (temporally predictable) flashes of light that were irrelevant to the task. Although the response to unpredictable flashes was also largely unaffected, we did find an additional late component in this response after DSP4 treatment. These results show that the noradrenergic innervation of the occipital cortex does not always regulate the extent to which visual stimuli are processed, but that noradrenergic neurotransmission may be activated in order to diminish excessive processing of unexpected stimuli.

Animals↗

Influence of drugs on brain neurotransmitters and behavioral states during development.

Neurotransmitters are present at very early stages of brain development. They may have trophic effects on maturation of target neurons and mediate the behavioral repertoire of the immature brain. Many centrally acting drugs which are used during pregnancy and early childhood for the treatment of e.g. hypertension, depression, epilepsy, sleep disorders, or hyperkinetism influence brain neurotransmitters and behavioral states. Disturbances observed later in life in animal and man, due to perinatal interference of such drugs with brain neurotransmitters and behavioral states, are not gross physical malformations but rather subtle behavioral and neurological symptoms such as hyperactivity, emotional lability, perceptual motor disturbances, attentional distractibility and sleep disturbances.

Behavior↗

Visual and auditory evoked potentials in different areas of rat cerebral cortex.

Visual and auditory evoked potentials were studied in the occipital, temporal, prefrontal and cingulate areas of the rat cerebral cortex. We found that both prefrontal and cingulate areas can respond to more than one sensory modality. The latencies of the response to light and sound, though slightly longer in these associative areas than in the two primary cortical regions, were still within the range of early sensory evoked responses (i.e. less than 50 ms).

Acoustic Stimulation↗

The importance of fetal/neonatal REM sleep.

The emergence of behavioral states is one of the most significant aspects of development. The rat is very immature at birth and in some structural and functional aspects of CNS (central nervous system) development it is comparable to a 7-month-old human fetus. At this stage of development synchronization of different state criteria is poorly organized. Infant rats spend very little time in wakefulness and, once asleep, they still display a very high level of motor activation, with frequent rapid eye movements and uncoordinated myoclonic jerks. Although it is questioned whether the activated state of sleep in the newborn rat is comparable to rapid-eye movement sleep (REM) in adults, it has been shown that the CNS displays an increased level of endogenous neuronal activation even in very immature animals during this state. To study the functional significance of REM in early life, rat pups were deprived of this state from 1 to 3 wk of age and tested as adults. In the rat, chronic suppression of REM by interfering with monoamines during early development induced hyperactivity, hyperanxiety, attentional distractability, sleep disturbances, reduced sexual performance and reduced cerebral cortical size. In studies using instrumental, surgical or other pharmacological treatments to suppress REM similar effects on the development of brain and behavior were found. Taken together, these findings point to a role for REM during early development, so that more attention should be given to the potential hazards of medicines (and/or pathologic conditions) which induce reduced levels of REM and or disturbed monoamine activities in the brain during late prenatal and early postnatal life.

Animals↗

Manipulation of vasopressin level in the cerebrospinal fluid of the rat by means of an easily interchangeable controlled-delivery Accurel mini-device.

The procedure described for the continuous release of vasopressin (VP) in the rat lateral ventricle via implantation of a VP-loaded Accurel/collodion mini-device has now been further developed, allowing the introduction, removal and exchange of the Accurel device through a polyethylene guide cannula. In this way, manipulation of the VP level in the cerebrospinal fluid can easily be accomplished. VP levels were measured by radioimmunoassay in liquor withdrawn from the cisterna magna.

Animals↗

6-Hydroxydopamine treatment does not affect the young rat's ability to modify its response when changing from food to water deprivation.

In this study we examined whether depletion of forebrain noradrenaline would affect latent learning as predicted on the basis of the role attributed to the dorsal noradrenergic bundle in attention. Either 6-hydroxydopamine (6-OHDA) or saline was injected into the lateral ventricles of male Wistar pups on postnatal day 12. Immediately after weaning the rats were food deprived and trained to choose the left arm of a Y-maze which contained food while the right arm provided access to water. Once they had learnt to enter the left arm they were allowed access to food but not to water for one day and then tested again. All the rats quickly adjusted their behavioural response to the fact that they were deprived of water. The 6-OHDA-treated rats' behaviour did not differ significantly from that of the controls.

Adaptation, Psychological↗

The role of the central monoaminergic system and rapid eye movement sleep in development.

Transmission of information in the brain is of a chemical nature. Neurotransmitters are present at very early stages of brain development, having trophic effects on maturation of target neurons as well as mediating the behavioral repertoire of the immature brain. Many centrally acting psychoactive drugs which are commonly used (also during pregnancy) for treatment of depression, asthma, hypertension, epilepsy, parkinsonism, hyperkinetism and other neurological and psychiatric disorders act directly on brain neurotransmitters (in particular monoamines) and behavioral states. Disturbances observed later in life in animals and man, as a result of early interference with brain neurotransmitters, using these drugs, are not gross physical malformations but are in fact subtle behavioral and neurological symptoms such as hyperactivity, emotional lability, attentional distractability and sleep disturbances, similar to symptoms observed in the minimal brain dysfunction syndrome.

Animals↗