Search PubMed⌕ Search

Biomedical subjects

W Meelis

Publications and source records attributed to W Meelis.

16 recordsLinked to original sources

Neurochemical characterization of hypothalamic neurons involved in attack behavior: glutamatergic dominance and co-expression of thyrotropin-releasing hormone in a subset of glutamatergic neurons.

The electrical stimulation of a specific hypothalamic area rapidly evokes attacks in rats. Noteworthy, attack-related hypothalamic structures were identified in all species studied so far. The area has been extensively mapped in rats, and its anatomical connections have been studied in detail. However, technical difficulties precluded earlier the precise identification of the neural elements mediating the aggressive effects of stimulation. It now appears that a dense and distinct group of glutamatergic cells expressing vesicular glutamate transporter 2 mRNA extends over the entire hypothalamic attack area. Rostral parts overwhelmingly contained glutamatergic neurons. In more caudal parts, glutamatergic and fewer GABAergic neurons were found. The remarkable similarity in the distribution of hypothalamic attack area and glutamatergic cell groups suggests that these cells mediate the aggressive effects of stimulation. Surprisingly, thyrotropin releasing hormone mRNA was co-localized in a subset of glutamatergic neurons. Such neurons were present at all rostro-caudal levels of the hypothalamic attack area, except for that part of the hypothalamic attack area extending into the ventro-lateral part of the ventromedial hypothalamic nucleus. Earlier data on the projections of hypothalamic thyrotropin releasing hormone neurons suggest that this subpopulation plays a specific role in attack behavior. Thus, we identified three neuronal phenotypes in the hypothalamic structure that is involved in the induction of attacks: glutamatergic neurons co-expressing thyrotropin releasing hormone, glutamatergic neurons without thyrotropin releasing hormone, and GABAergic neurons dispersed among the glutamatergic cells. Assessing the specific roles and connections of these neuron subpopulations would contribute to our understanding of the mechanisms underlying attack behavior and aggression.

Aggression↗

Neuronal substrate of electrically induced grooming in the PVH of the rat: involvement of oxytocinergic systems?

Electrical stimulation of the paraventricular (PVH) and adjacent hypothalamic area evokes self-grooming behaviour. Current intensity thresholds for grooming can be obtained depending on the exact localization of the electrode site. Sites localized at greater distance of the center of the grooming area evoke grooming at greater latencies and higher current intensity, or no grooming at all. Results are compared with injections of neuroactive substances into the PVH from previous studies, which showed a similar site specificity for grooming. We found similarity in the distribution of electrode sites in the paraventricular and anterior hypothalamic areas at which grooming is induced, and hypothalamic immunoreactive oxytocinergic neurons and fibres. In addition, we reported earlier that oxytocin infusions into the PVH in resting animals induce grooming, in contrast to other grooming-related peptides, such as alpha-melanocyte-stimulating hormone. We hypothesize that electrical stimulation may induce grooming by activation of oxytocinergic systems originating from the PVH.

Animals↗

Effect of environmental stressors on time course, variability and form of self-grooming in the rat: handling, social contact, defeat, novelty, restraint and fur moistening.

Grooming is often related to dearousal following stressors. Interestingly, electrical and chemical stimulation of the paraventricular nucleus of the hypothalamus (PVH), at levels that are known to activate the hypothalamus-pituitary adrenal axis (HPA), also elicits grooming. At the level of the PVH, the neuroendocrine stress response is apparently still linked to the behavioural response to stressors. However the precise nature of this relation is not fully understood. Here we report on grooming in rats following exposure to different stressors which are known to activate the HPA axis. Stressors such as handling, restraint, novelty, encounters with aggressive or non-aggressive conspecifics, or moistening the fur, change the amount and time course of grooming upon return in the home cage, as compared with controls that are just handled. However, the amount of grooming is not directly related to the strength of the stressor. Defeated intruders groom less upon return in their home cage. Novelty and non-aggressive encounters with conspecifics reduce the variation in the amount of grooming between rats. The time course of grooming over the 20-min observation period also differs between treatments. Following restraint, or exposure to non-aggressive conspecifics, grooming first increases and then decreases. Moistened rats immediately start grooming which subsequently decreases. Rats used as intruders in the territory of another rat maintain a constant low level of grooming. Rats placed in a novel cage steadily increase grooming during the 20-min observation period. These results suggest that grooming cannot be simply understood as an immediate response necessary to reduce arousal following stressors. Following exposure to a stressor, grooming rather seems temporary suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

Periaqueductal gray lesions do not affect grooming, induced electrically in the hypothalamic paraventricular area in the rat.

Electrical stimulation inducing behavioral responses from the hypothalamus seems to activate systems involved in the execution phase of the behaviour rather than in the introductory or decision-making phase. However, the pathways involved are not fully understood. Projections originating from hypothalamic areas involved in specific behavioral responses are rather complex. The periaqueductal gray (PAG) has been proposed to be an essential output station of hypothalamic behavioral mechanisms. Here we report that lesions of the periaqueductal gray area have no effect on grooming responses evoked by electrical stimulation of the hypothalamic paraventricular area. Neither threshold current intensities needed to evoke grooming, nor latencies were affected 7 or 14 days after lesioning. The lesions caused severe behavioural deficits. Animals did not drink or eat spontaneously, had problems with motor coordination and sometimes showed strong defensive reactions upon touch. However, their grooming responses induced by hypothalamic stimulation were not changed. The PAG may have a modulatory role on grooming behaviour; however, this modulatory effect apparently is overruled during electrical stimulation of the hypothalamus.

Animals↗

Behavioural effects of NMDA injected into the hypothalamic paraventricular nucleus of the rat.

Electrical stimulation of the hypothalamic paraventricular nucleus (PVH) and of the adjacent dorsal hypothalamic area (DHA) evokes grooming behaviour. Microinjections of low doses of kainic acid, an agonist of the kainate type of glutamate receptors, into the same area evokes the same behaviour. To test whether other glutamate receptors are involved, microinjections with N-methyl-D-aspartic acid (NMDA) were made into the PVH/DHA area and the behaviour was observed. From the total observation time (30 min) up to 73% was spent on grooming, accompanied by yawning. Pronounced feeding behaviour was also noticed at 3 injection sites but not until 23 min after injection. Conclusions are that neurones within the PVH/DHA area are involved in grooming behaviour, possibly via glutamatergic innervation. The interaction between grooming and feeding behaviour at the level of the PVH is discussed.

Animals↗

Interactions between simultaneously activated behavioral systems in the rat.

Interactions between electrically induced attack and teeth-chattering from 1 electrode and grooming from another were examined in male albino rats. The interaction between electrically induced attack and deprivation-induced feeding, as well as the effect of food deprivation on attack, was also studied. Results indicate that attack appears to be a dominant response, for it suppressed grooming and feeding at a low level of activation. On the other hand, it was not affected by simultaneously induced grooming or feeding. However, food deprivation decreased the threshold for attack, leaving attack latency, attack form, or bite targets unaffected. Teeth-chattering, suggested to be related to attack and flight, was also a dominant response. Results suggest that interactions between behavioral systems are in favor of the systems that must act acutely on activation in order to survive. Apparently, the regulations governing these interactions are represented in the functional organization of the brain.

Aggression↗

Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat.

The hypothalamic response area for electrically induced locomotion was determined using moveable electrodes and discriminant analysis as an appropriate statistical technique. At 241 out of 641 stimulated sites locomotion was induced. The distribution of locomotion sites is relatively diffuse. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probability of inducing the response. The response is considered to be mediated by fibres of the subpallido-pedunculopontine system, which includes the mesencephalic locomotor region. Different categories of exploratory and flight-directed locomotion were distinguished, and response areas for both categories were determined. In addition the response area for escape jumps was delimited. Exploratory locomotion is mainly induced from the lateral hypothalamus, while flight-directed locomotion and escape jumps are evoked from the medial hypothalamus. The response area for exploratory locomotion reflects the lateral hypothalamic distribution of the subpallidal projection to the mesencephalic locomotor region. A diffuse substrate for flight behavior seems to occupy almost the entire medial hypothalamus. It is concluded that a locomotor subroutine subserving different behavioural mechanisms can be activated at many hypothalamic sites.

Animals↗

Hypothalamic substrates for brain stimulation-induced attack, teeth-chattering and social grooming in the rat.

In this paper the boundaries of the hypothalamic response areas for brain stimulation-induced attack, social grooming and teeth-chattering were delimited. A total of 641 hypothalamic sites in 71 male CPW/WU Wistar rats were electrically stimulated. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate and low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high. Neuroanatomical correlates of these response areas are discussed. The response area of attack is suggested to be an integrative processing area, stimulation of which overrules some aspects of integration and directly activates the behavioural program of attack. Although some authors consider all three responses to be part of the behavioural repertoire of aggression, the response areas are not identical. Social grooming and attack are considered to be induced from different neural systems. Similarly, attack and teeth-chattering have been shown to derive from different neural mechanisms, despite substantial overlap of both response areas. It is suggested that teeth-chattering derives from the simultaneous activation of both attack and flight tendencies. No further distinctions with respect to threshold current intensities can be made within responses areas. However, the underlying neural substrates are not homogeneous, for thresholds vary along the course of individual electrodes.

Aggression↗

Hypothalamic substrates for brain stimulation-induced grooming, digging and circling in the rat.

Despite a great number of studies concerned with the induction of specific behavioural responses from the rat hypothalamus by electrical brain stimulation, hypothalamic response areas and underlying neural substrates have never been determined accurately. In this study the boundaries of the hypothalamic response areas for grooming, digging and circling were delimited using moveable electrodes, an enriched environment containing a variety of goal objects, and an appropriate statistical technique. A total of 641 hypothalamic sites in 71 male CPB/WU Wistar rats were electrically stimulated. Results are plotted on a detailed stereotaxic brain atlas of the rat hypothalamus. Positive sites for any behavioural response cluster into restricted hypothalamic areas. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probabilities of inducing the behavioural response concerned. Each response has its own response area where probabilities are high, although there may be overlap. Even within response areas a distinction can be made between areas in which the response can be induced at relatively high or low threshold current intensities. Lowest threshold sites within electrode tracks are often clustered. In search of neuroanatomical correlates, grooming is related to the distribution of ACTH-immunoreactive neural elements, digging is related to the distribution of efferent fibres from the bed nucleus of the stria terminalis, and circling is related to the distribution of dopaminergic fibres of the nigrostriatal pathway. The results clearly point to the stimulation site being the most important determinant of the evoked behavioural response. Evidently behavioural specificity does exist within the hypothalamus.

Animals↗

Discriminant analysis of the localization of aggression-inducing electrode placements in the hypothalamus of male rats.

Over 400 sites in the hypothalami of 270 male CPB/WE-zob rats were electrically stimulated in order to induce fights between males. The localization of electrodes inducing fights seems to differ from the localization of electrodes in which no fights can be induced. The differences in localization were detected and tested by a non-parametric discriminant analysis. The results were plotted by computer in a stereotaxic atlas of the hypothalamus of the CPB/WE strain. The method delimits areas within the hypothalamus where the probability to induce aggression is high, intermediate or low. Moreover, the procedure allows discrimination between areas where the thresholds for attack behaviour are generally lower than elsewhere and where the fiercest forms of attack are induced. None of the areas delimited coincide with a classical subdivision of the hypothalamus. Parts of the perifornical, anterior, lateral and ventromedial hypothalamus seem to be involved. The methods developed here may help to relate stimulation-induced aggression to other characteristics of the 'aggressive' area which cannot be obtained directly from fighting rats such as cytological, endocrinological, biochemical or physiological data. In addition, the procedure may help to settle disputes on the specificity of the localization of neural substrates of other stimulation-induced behaviours. The methods to discriminate between overlapping 3-dimensional reconstructions validated here for aggressive responses, can also be applied to other types of stereotaxic data and other types of effects, such as electrical, hormonal or other physiological responses. They may be especially useful if the localization of the neural population involved is not yet known, and unknown current-spread or diffusion of substances complicates the interpretation of stereotaxic data.

Aggression↗

A locked, non-rotating, completely embedded, moveable electrode for chronic brain stimulation studies in freely moving, fighting rats.

A light-weight, yet rugged moveable electrode assembly is described for chronic brain stimulation studies in small-brained animals. The assembly can be completely embedded in a smooth, unobtrusive dental cement cap and is therefore suitable for use in fighting experiments, where collisions with partners and cage walls will limit the use of other assemblies. It permits a variable electrode distance penetration of 3 mm in 75 mu-steps by using a separate unlocking turning-key. This design excludes the possibility of inadvertent displacement of the electrode tips by the animal itself. Since the electrode itself does not rotate during displacement, extra damage arising from possible eccentricity is avoided. The assembly has been used in a number of hypothalamic penetrations, demonstrating its usefulness and reliability.

Aggression↗

Aggression induced by stimulation of the hypothalamus: effects of androgens.

Aggressive behavior between male rats induced by electrical stimulation of the hypothalamus (ESH) is stimulated by androgens. This was demonstrated by recording the changes in threshold current intensities (the amount of current needed to induce attack behavior in 50% of the trials), just before castration, after castration, during subsequent treatment with high doses of testosterone propionate, and finally during oil treatment. The results demonstrate that, to induce the same aggressive responses, in absence of androgens more electrical current is needed than when these hormones are present in the general circulation of the ESH stimulated animals.

Aggression↗

Anti-aggressive effect of a new phenylpiperazine compound (DU27716) on hypothalamically induced behavioural activities.

Using the same hypothalamic electrodes, the following behaviour was evoked in male rats by electrical stimulation at roughly equal current intensities: attacks on a partner, teeth-chattering, switch-off behaviour and locomotion. Current thresholds were determined for each behaviour following the intraperitoneal administration of saline or DU27716, a new phenylpiperazine compound with interesting inhibitory effects on territorial and intermale aggression. DU27716 raised current thresholds for attack and teeth-chattering beginning at the lowest dose (4 mg/kg), whereas there was no effect on switch-off behaviour, and only a slight but significant effect on locomotion thresholds at the highest dose (8 mg/kg). The results provide support for the hypothesis that DU27716 possesses behaviourally selective, anti-aggressive properties, and illustrate the usefulness of hypothalamically induced behaviours as a pharmacological model.

Aggression↗