Effect of Lateral Preoptic Area Lesion on Sleep Wakefulness and Thermoregulation In Cold Acclimatized Rats.

Hypothalamic temperature (Thy) alteration is one of the important stimuli that brings about thermoregulatory measures including the changes in wakefulness and muscular activity. The role of the lateral preoptic area (lPOA) in thermoregulation and sleep is well documented. But it is not known whether the integrity of the lPOA is essential for bringing about the changes in sleep-wakefulness (S-W) and thermoregulation in cold ambient temperature (Ta). Neurotoxic lesion of the lPOA resulted in an increase in wake period and core body temperature (Tb) and no change in Thy. Unlike, normal animals, as reported earlier, there was further increase in Tb of the lPOA lesioned rats on acute cold exposure, but the Thy remained unaltered throughout the 28 days of continued cold exposure. The findings demonstrate that the lPOA lesioned rats have lost the ability to reset Thy which may be necessary for thermoregulation during cold exposure. Moreover, increased wake period lasted only 7 days in lesioned, compared to 14 days in normal animals. Less efficient restoration of Tb, and less prolonged wake period during continued cold exposure, are probably the result of the inability of the lPOA lesioned rats to lower Thy, which is necessary to bring about the thermoregulatory measures.

Hypothalamic temperature: A key regulator in homeostatic restoration of sleep during chronic cold exposure in rats.

Exposure to cold ambient temperature (Ta) affects sleep-wake (S-W) state. The vigilance states on the other hand influence thermal status of the animals. Simultaneous recording of body temperature (Tb) with S-W is crucial to understand the homeostatic relationship between the two. In the present study we recorded both Tb and hypothalamic temperature (Thy) along with S-W, during acute and chronic exposure to mild cold (Ta). Electrooculogram (EOG), electroencephalogram (EEG) and electromyogram (EMG) electrodes were chronically implanted in rats to assess S-W. A thermocouple, near the preoptic area, and radio transmitter in the peritoneum, were implanted, to record Thy and Tb respectively. After three days of baseline recordings of S-W, Thy and Tb at Ta of 26°C, the rats were exposed to mild cold Ta (18°C) for 28 days. All the parameters were recorded during cold exposure and also for five days after the termination of cold exposure. On the first day of cold exposure there was a decrease in slow wave sleep and paradoxical sleep, but they were restored by the 21st day of continued exposure. The Thy remained decreased throughout the cold exposure. Though the Tb showed a slight decrease on the first day of cold exposure, there was no appreciable change during the subsequent days. The Thy came back to near pre exposure level on termination of cod exposure. The decrease in Thy during mild cold exposure would have triggered cold defense mechanisms. Increase in wakefulness during acute cold exposure and non-shivering thermogenesis during chronic cold exposure are probably responsible for the maintenance of Tb. Decrease in Thy is probably the key trigger for initiating thermoregulatory measures to maintain Tb and homeostatic restoration of sleep.

Warm sensitive neurons of the preoptic area regulate ambient temperature related changes in sleep in the rat.

Warm sensitive neurons (WSN) play a major role not only in body temperature regulation, but also in sleep regulation. The present study was undertaken to investigate the role of WSN of the preoptic area (POA) in mediating the ambient temperature (Tamb) related changes in sleep. The effect of Tamb changes on sleep and body temperature was studied in rats before and after destruction of WSN of the POA by local intracerebral injection of capsaicin. Though the rats preferred 27°C Tamb, they slept maximum at 30°C. After destruction of WSN of the POA, slow wave sleep (SWS) peak was brought down to 27°C, which was the preferred Tamb of the rats. This indicates that WSN of the POA mediate the increase in SWS, at temperatures higher than preferred Tamb. On the other hand, in WSN destroyed rats, rapid eye movement (REM) sleep was maximum at 33°C. It suggests that the REM sleep generation is under inhibitory control of the WSN of the POA. The study supports several earlier reports that the neurons of the POA play a key role in coordinating sleep and body temperature regulation.

Changes in hypothalamic and body temperatures during 24 hours in rats.

The available information on simultaneous assessment of body and hypothalamic temperatures in rats are lacking. In the present study these temperatures were recorded for 24 h, on three alternate days, in rats maintained at an ambient temperature of 26±1°C. Hypothalamic temperature was significantly higher than body temperature during the night. In nocturnal rats the magnitude of circadian variation in hypothalamic temperature was higher than body temperature. Though maintained at different levels, both the temperatures showed closely associated diurnal changes throughout the 24 h period.

Sleep and sleep disorders.

Sleep is a complex neurological state, with its primary function of providing rest and restoring the body's energy levels. The importance of sleep could be seen from the fact that people spend about one-third of their lifespan in sleep. Normal human sleep is divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and the alteration between NREM and REM occurs about 4-5 times during a night of normal sleep. Human NREM sleep could be classified into four stages, namely, stage I, II, III and IV, representing successively deeper stages of sleep. Sleep is an active rhythmic neural process produced by several brain areas, of which the preoptic and other basal forebrain areas play a major role in the generation of NREM sleep. Interaction of the pedenculo-pontine and lateral dorsal tegmental areas with the dorsal raphae nucleus and locus coeruleus, is important for REM sleep generation. Suprachiasmatic nucleus of the hypothalamus and the pineal gland ensure that sleep and wakefulness follow a circadian periodicity of nearly 24 hours. Alterations in the quality, quantity and pattern of sleep result in sleep disorders. Persistent and repeated interruption of sleep affects the health of an individual. Undiagnosed and untreated wake/sleep complaints cause not only misery to the sufferer, but it also has socio-economic consequences. Sleep disorders cover a wide spectrum of diseases. Though there are more than 100 identified sleep/wake disorders, most sleep complaints can be categorised into five, namely, hypersomnia, insomnia, circadian rhythm disorders, parasomnias, and sleep disorders associated with mental, neurological, and other medical disorders. Researches during the last 50 years, and the advances made in clinical sleep medicine, have lead to more effective treatments for the myriad human sleep disorders. It is not possible to assign a specific reason for many of the sleep disorders, but some aspects of sleep and wakefulness are genetically influenced. But, most commonly, sleepiness during waking hours, results from volitional or forced sleep deprivation during previous nights, due to social, economic and environmental reasons. So, public awareness about sleep disorders should be an essential part of any programme aimed at global management of sleep disorders.

The medial septum acts through the medial preoptic area for thermoregulation and works with it for sleep regulation.

The chronic changes in sleep-wakefulness (S-W), body temperature (Tb), locomotor activity (LMA) and thermal preference were studied in male Wistar rats after the destruction of neurons in both the medial preoptic area (mPOA) and the medial septum (MS) by intracerebral injection of N-methyl-D-aspartic acid. An increase in the Tb, and a preference for higher ambient temperature (Tamb) of 30 degrees C were observed after the combined lesion of the mPOA and the MS. Similar changes were reported to occur after the lesion that was restricted to the mPOA. But these alterations were in contrast to the decrease in Tb and preference for lower Tamb, observed after the MS lesion. The thermostat of the brain would have been reset at a higher level after the combined lesion, as there was an increase in Tb, along with a preference for a higher Tamb, and an increase in LMA. There was a reduction in the frequency and the duration of the slow wave sleep (SWS) episodes, and a reduction in the frequency of the paradoxical sleep (PS) episodes after the combined lesion. The destruction of the MS neurons was probably responsible for the reduction in the frequency of SWS, whereas the loss of mPOA neurons was responsible for the decrease in the duration of SWS and frequency of PS. It can be suggested that the MS exerts its influence on thermoregulation through the mPOA. However, the MS and the mPOA seem to play independent, but complementary roles in sleep promotion.

Sleep changes during chronic cold exposure showed that the homeostatic requirement of sleep is reduced in the medial preoptic area lesioned rats.

The effects of chronic exposure to a mildly cold ambient temperature (T(a)) of 18 degrees C on sleep wakefulness (S-W) and brain temperature (T(br)) were studied in the medial preoptic area (mPOA) lesioned male Wistar rats. Electroencephalogram (EEG), electrooculogram (EOG) and electromyogram (EMG) electrodes were chronically implanted to assess S-W, and a thermocouple above the dura to record the T(br). After three recordings (24 h each) of S-W and T(br) at 24 degrees C, N-methyl D-aspartic acid (NMDA) was intracerebrally injected to produce bilateral destruction of neurons in the mPOA. There was decreased sleep and increased T(br) even four weeks after the mPOA lesion. T(a) of the environmental chamber was then reduced to 18 degrees C, and the S-W and T(br) were again recorded for 24 h each on the 1st, 7th, 14th, 21st, and on 28th days of continuous exposure to the mild cold T(a). Exposure to the cold produced further decrease in sleep and increase in the T(br). However, sleep came back to the pre-exposure level by the 14th day. An increase in the duration of sleep episodes was responsible for the restoration of sleep during chronic cold exposure. The study showed that the requirement of sleep was reset at a lower level in the mPOA lesioned rats. The mPOA lesion affected the sleep maintenance and sleep initiation, though the latter became evident only during chronic cold exposure. The magnitude of the acute changes in T(br) and S-W were less in the lesioned rats, as compared to those observed in the normal rats exposed to similar cold T(a). On the basis of these observations, it could be proposed that the mPOA plays some role in cold induced changes in thermoregulation and sleep regulation. The T(br) remained elevated throughout the period of cold exposure. Resetting of the T(br), at a higher level may be part of the homeostatic readjustment to restore sleep.

Repeated intracerebral microinjections: efficacy in studying brain functions.

Injection of chemicals into the brain has been considered as an important technique to study various functions of the brain. In these studies, as a rule, only one bilateral injection is given in one animal. This study was undertaken to evaluate the quality of the body temperature data obtained after first and second injections of methoxamine and artificial cerebrospinal fluid into the medial preoptic area. Though there was quantitative decrease in the effects produced after the second injection of the drug, there was no significant change in the effects produced by the second injections of artificial cerebrospinal fluid, which was used as a vehicle. Results of this study support the earlier recommendation to perform only one injection in any of the brain sites for evaluating the effect of any drug. But the vehicle can be administered as a second injection, without compromising on the quality of data.

Why the medial preoptic area is important for sleep regulation.

The medial preoptic area (mPOA) is one of the many areas in the brain that control sleep. Apart from sleep, the mPOA is important for the regulation of body temperature, and other important body functions aimed at energy homeostasis. In sleep regulation, the major function of this area is to maintain sleep. Though the mPOA controls sleep and body temperature through independent neuronal circuits, it is essential for organising the sleep architecture, as per the thermoregulatory requirement. The functional integrity of the mPOA may be essential for the regulation of energy homeostasis, in response to alterations in the ambient temperature, heat producing physical activity and sleep-wakefulness. Thus, the mPOA forms part of the brain that integrates regulations aimed at preservation of self. The mPOA is important for maintaining the "set point" for not only body temperature, but it is also important for maintaining the "set point" for several physiological parameters including sleep-wakefulness.

Role of catecholaminergic terminals in the preoptic area in behavioural thermoregulation in rats.

This study was conducted to find out the role of the catecholaminergic terminals in the preoptic area (POA) in selection of ambient temperature in rats. The adult male Wistar rats (n = 6) were allowed to choose between three ambient temperatures (24 degrees C, 27 degrees C and 30 degrees C). Rats could move about freely from one ambient temperature to another, in a specially designed environmental chamber having three interconnected compartments, which were maintained at the above mentioned temperature. The results show that the normal rats preferred to stay at 27 degrees C both during day and night. After the lesion of catecholaminergic terminals in the POA with 6-hydroxydopamine (6-OHDA), the animals preferred 24 degrees C on the third and seventh day and 27 degrees C on the fourteenth and twenty first day after lesion. The alteration in thermal preference was associated with an elevation of rectal temperature. The study suggests that the catecholaminergic terminals of the POA play an important role in integrating behavioural and non-behavioural thermoregulatory responses, but in its absence the rest of the brain takes over some of its functions.

Effect of ambient temperature on brain temperature and sleep-wakefulness in medial preoptic area lesioned rats.

The changes in brain temperature and sleep-wakefulness were studied in rats during their exposure to different ambient temperatures of 18 degrees C, 24 degrees C and 30 degrees C, before and after N-methyl D-aspartic acid lesion of the medial preoptic area. The medial preoptic area lesion produced a decrease in sleep, and increase in brain temperature except at 30 degrees C. Increase and decrease in brain temperature with slow wave sleep and paradoxical sleep respectively, were observed both in normal and lesioned rats. Sleep-wakefulness and brain temperature cycle durations were increased and their frequencies decreased at higher ambient temperature in normal rats. After the medial preoptic area lesion, sleep-wakefulness cycle duration was decreased and frequency increased at 30 degrees C. There was no significant change in brain temperature cycles at higher ambient temperature in lesioned rats. The medial preoptic area, in normal rats, possibly interlinks the neuronal circuits involved in regulating brain temperature and sleep-wakefulness cycles. The medial preoptic area is essential for increasing the sleep-wakefulness cycle duration with higher ambient temperature. The possible contribution of the increased brain temperature variation in producing sleep-wakefulness changes cannot be ruled out. The results of the study show that this area may serve as a fine tuning mechanism which helps to interlink the sleep-wakefulness with the thermoregulation.