H.N. Mallick

Differences in the effects of medial and lateral preoptic lesions on thermoregulation and sleep in rats

The effects of the destruction of the medial preoptic area and the lateral preoptic area with N-methyl-d-aspartic acid on sleep-wakefulness, brain temperature and thermoregulation were studied in two groups of male Wistar rats. Electroencephalogram, electrooculogram and electromyogram, along with brain temperature, were recorded for 3 days, prior to the destruction of the medial preoptic area and the lateral preoptic area, and on the 7th and 21st days after the destruction of these areas. The thermoregulatory capacity of the rats was assessed by recording their brain temperature when they were exposed to severe cold (5+/-1 degrees C) and heat (37+/-1 degrees C) before and after the lesion. Though sleep was decreased after the destruction of both the medial preoptic area and the lateral preoptic area, paradoxical sleep was reduced only by the destruction of the medial preoptic area. Decrease in sleep after the medial preoptic area lesion was brought about by a decrease in the duration of the slow wave sleep episodes and the frequency of paradoxical sleep episodes. Decrease in sleep after the lateral preoptic area lesion was brought about by a decrease in the frequency of slow wave sleep episodes. There was a significant increase in brain temperature after the medial preoptic area lesion but not after the lateral preoptic area lesion. The rats with lesion in the medial preoptic area showed deficits in thermoregulation on exposure to cold, while those with the lateral preoptic area lesion showed deficits in heat defense ability. The present findings suggest that the medial preoptic area and the lateral preoptic area regulate sleep by different modalities and that there is an anatomical segregation of heat and cold defense functions within the basal forebrain.

Medial preoptic alpha-2 adrenoceptors in the regulation of sleep-wakefulness

Adrenergic alpha 2 agonist (clonidine) and its antagonist (yohimbine) were locally applied to the medial preoptic area (mPOA), to find out the role of alpha 2 receptors at this brain region in the regulation of sleep-wakefulness. Clonidine produced arousal, whereas yohimbine induced sleep in freely moving animals. Behavioural arousal produced by clonidine administration was accompanied by EEG synchronization. The alpha 2 receptor as the probable site of action of externally applied norepinephrine (NE), is discussed.

β-Adrenergic modulation of male sexual behavior elicited from the medial preoptic area in rats

This study was aimed at investigating the role of the adrenergic mechanism in the medial preoptic area (mPOA) in sexual arousal and copulatory performance. Saline, norepinephrine (NE), phenoxybenzamine (PBZ) and propranolol (PROP) were injected into the mPOA in different groups of rats. NE application (3 micrograms) facilitated the male sexual behavior by increasing sexual arousal and copulatory performance. On the other hand, application of PROP and PBZ produced inhibition of male sexual behavior. Effects produced by low doses of PROP were more significant than PBZ. The results, viewed in the light of other available reports, suggest that the mPOA beta-adrenergic mechanism is important in the elaboration of male sexual behavior.

Stereotaxic assembly and procedures for simultaneous electrophysiological and MRI study of conscious rat

A stereotaxic restraining assembly was designed and developed for simultaneous electrophysiological recordings and functional MRI (fMRI) data acquisition from a conscious rat. The design of the nonmagnetic stereotaxic apparatus facilitated the restraining of head and body of the unanesthetized conscious animal during MRI experiments. The apparatus was made of Teflon and Perspex materials with an appropriate size and shape for a 4.7 T / 40 cm animal MRI scanner. Electrodes made from nonmagnetic silver wire were implanted on the skull for recording the electroencephalogram (EEG), the electro‐oculogram (EOG), and the electromyogram (EMG), while polycarbonate screws were used for anchoring the electrode assembly. There were no major distortions or artifacts observed in the electrophysiological tracings and MR images. Electrophysiological recordings during fMRI acquisitions are useful to study different neurophysiological mechanisms of sleep and pathophysiology of seizure activity. Integration of electrophysiological recordings (with their good temporal resolution) and MRI (with its superior spatial resolution) is helpful in characterizing the functional state of different brain regions. Magn Reson Med 49:962–967, 2003.

Functional MRI shows activation of the medial preoptic area during sleep.

Changes in the activity of the basal forebrain sleep regulating areas were studied noninvasively in conscious rats by employing functional magnetic resonance imaging (fMRI). Sleep-wakefulness (S-W) stages were identified with the help of electrophysiological recordings carried out simultaneously. An increase in the signal intensity was observed in the medial preoptic area (mPOA) during sleep indicating a heightened activity of neurons in this area. In some rats, there was a decrease in the activity of the fronto-parietal cortex. The sleep-induced increase in activity in the mPOA and decrease in the fronto-parietal cortex are in relation to their levels in the awake state. The findings helped to localize the critical area for the maintenance of slow wave sleep at the mPOA. These results further corroborate some of the previous suggestions based on neurotoxic lesion, chemical stimulation and electrophysiological recordings.

Sensory Modulation of the Medial Preoptic Area Neuronal Activity by Dorsal Penile Nerve Stimulation in Rats

The study was aimed at finding out the influence exerted by the genital afferents on the medial preoptic area (mPOA), which plays a pivotal role in the regulation of male sex behavior. To fulfil this objective, the effects of stimulation of the dorsal penile nerve (DPN) on the activity of 82 mPOA neurons were studied. The base line firing rates of the mPOA neurons, studied by extracellular recording, ranged between 0.5 and 38.5 Hz (mean 7.18 +/- 7.91). The stimulation of the DPN (20 Hz, 0.4 msec. 70 microA) influenced 79.69% of the neurons studied. Though increased firing was the predominant influence produced (50%), decreased firing was also seen in a few (29.69%). The excited and inhibited neurons were randomly distributed within the mPOA. Neurons located in the lateral and posterior hypothalamus were not affected by the DPN stimulation. The stimulation parameters used in this study did not produce any change in the systemic arterial pressure and heart rate. The results provide electrophysiological evidence of afferent inputs from the male sex organ to the mPOA, which is an important area controlling male sex behavior.

Tonic activity of α1 adrenergic receptors of the medial preoptic area contributes towards increased sleep in rats

Several studies have suggested that noradrenergic afferents to the medial preoptic area might be involved in hypnogenesis and in lowering the body temperature, and that the alpha1 adrenergic receptors might be mediating these responses. This study was undertaken to find out the changes in sleep-wakefulness and body temperature in rats, when these adrenergic receptors of the medial preoptic area are blocked by alpha1 selective antagonist, prazosin. Adult male Wistar rats were chronically implanted with electrooculogram, electroencephalogram and electromyogram electrodes for sleep-wakefulness assessment, and a bilateral guide cannula for microinjection of prazosin at the medial preoptic area. A radio-transmitter was implanted in the abdomen for telemetric measurement of body temperature in four groups of rats. Sleep-wakefulness was also assessed telemetrically in four other groups of rats. Sleep-wakefulness recordings from these rats were done in a specialized chamber, where they could move about freely and select the ambient temperature which they prefer. Prazosin induced a dose dependent increase in wake period and in body temperature, when microinjected into the medial preoptic area. Results suggest that preoptic alpha1 adrenergic receptors mediate hypnogenic and hypothermic responses. It is proposed that the noradrenergic afferents to the medial preoptic area, by tonic activation of alpha1 adrenergic receptors, contribute towards increase in sleep especially during the daytime.

The septal area, site for the central regulation of penile erection during waking and rapid eye movement sleep in rats: A stimulation study

The effects of electrical stimulation to the septum on penile erections in rats were examined to clarify the mechanisms for regulation of erectile responses during different states of vigilance. Penile responses were assessed by changes in pressure in the corpus spongiosum of penis (CSP) and electromyography (EMG) of the bulbospongiosus (BS) muscle. In anesthetized and un-anesthetized rats, stimulation in and around the septum induced three erectile patterns; 1) a Normal type response, which was indistinguishable from a spontaneous erection, characterized by a slow increase in CSP pressure with sharp CSP pressure peaks associated with BS muscle bursts, 2) Mixed type response, in which high frequency CSP pressure peaks were followed by a Normal type response, and 3) a Prolonged type response, evoked only in the anesthetized rat, consisting of a single sharp CSP peak followed by a slow increase in CSP pressure and a return to baseline with multiple subsequent events repeated for up to 960 s. In addition, a Micturition type response was also observed involving high frequency CSP pressure oscillations similar to the pressure pattern seen during spontaneous micturition. We found that erections were induced after stimulation to the lateral septum (LS), but not from the medial septum (MS). In anesthetized rats, a few responses were also obtained following stimulation of the horizontal limb of diagonal band (HDB). In un-anesthetized rats, responses were also induced from the HDB and the ventral limb of diagonal band (VDB) and the adjoining areas. The effective sites for eliciting erection during rapid eye movement (REM) sleep were located in the dorsal and intermediate parts of the LS, whereas the ventral part of the LS was the most effective site for eliciting erections during wakefulness. These results suggest a functional role for penile erection in the septum, and further suggest that subdivisions of the LS may have different roles in the regulation of penile erection during wakefulness and REM sleep.