G. Stock

Cardiovascular changes during arousal elicited by stimulation of amygdala, hypothalamus and locus coeruleus

Experiments were performed in chronically operated cats first awake and thereafter anesthetized with pentobarbitone, 16-20 mg/kg i.v. Stimulation of the central amygdala in awake cats elicited an arousal reaction seen in cortical and hippocampal EEG, and in muscle activity of dorsal neck muscles. Concomitantly therewith were autonomic system reactions resulting in a decrease in aortic blood flow distal to the renal arteries, an increase in arterial blood pressure, a tachycardia during, and a short-lasting bradycardia at the end of stimulation. In slightly anesthetized cats the cardiovascular reactions were found to be qualitatively similar. If the postero-lateral hypothalamus or the locus coeruleus complex were stimulated in cats first awake and thereafter anesthetized, similar arousal reactions and similar cardiovascular changes were obtained as with amygdaloid stimulations. However, the onset and magnitude of the response were more abrupt and more marked than those obtained by amygdaloid stimulations. Recordings of single unit activity within the central amygdala during spontaneously occurring changes in the level of arousal showed that amygdaloid units (n = 10) discharged at a rate of 7-14 impulses/sec during wakefulness whereas during slow wave sleep (n = 5) the discharge was only 2-9 impulses/sec. The hypothesis is put forward that the amygdala integrates behavioral and cardiovascular changes during arousal.

Sexual dimorphism of blood pressure: Possible role of the renin-angiotensin system

The prevalence of hypertension in men is higher than in women and the onset of this disease is earlier in male than in female subjects. In spontaneously hypertensive rats, males also have higher blood pressures than females. Evidence from epidemiological, physiological, molecular biological and morphological studies concerning this sexual dimorphism is reviewed. We demonstrate that the gonadal steroids testosterone and estrogen have important effects on the gene regulation of the renin-angiotensin system. This may in part contribute to the sexual dimorphism in blood pressure control. The direct effect of steroid hormones on genes related to hypertension provides a suitable paradigm to improve our understanding of molecular and cellular mechanisms of cardiovascular control.

Baroreceptor reflex during arousal induced by electrical stimulation of the amygdala or by natural stimuli

Baroreceptor control of heart rate was studied in 14 unanaesthetized cats during rest and arousal induced by either electrical stimulation of the central nucleus of the amygdala or by natural stimuli. The baroreceptor reflex was elicited by i.v. injections of angiotensin II and the sensitivity of the vagal component of the reflex expressed as the regression coefficient of the relationship between the systolic blood pressures of successive arterial pulses and their pulse intervals. Baroreceptor reflex sensitivity was reduced by all types of arousing procedure studied; an effect assumed to be a part of integrated cardiovascular adjustments accompanying arousal. Further studies in slightly anaesthetized cats were performed in order to investigate the time-course of such changes in reflex sensitivity. Th inhibition of the vagal component of the reflex did not last for the entire period of the electrically elicited arousal and it is suggested, therefore, that this might reflect the activation of mechanisms which limit orienting behaviour. Overall, these results indicate that the central nucleus of the amygdala may be involved in a transient integration of cardiovascular and behavioural responses during arousal.

Resistance to Tonic-Clonic seizures after amygdaloid kindling in cats

Abstract Tonic-Clonic seizures induced by amygdaloid stimulation in cats are followed by a period during which the threshold for the induction of subsequent seizure activity is elevated (postictal refractory period). The duration of this change is 2 to 5 h in kindled cats and 30 to 60 min in nonkindled cats. Arterial blood pressure, heart rate, and cortical and subcortical EEG recordings were taken as indices of seizure activity. Using these parameters, especially the hemodynamic changes, it was shown that the amygdaloid complex is not functionally inactive during the postictal refractory period but rather shows excitability which compares with prekindling values.

Sensory input to single neurons in the amygdala of the cat.

We determined functionally the afferent projections from exteroceptors and enteroceptors (visceral receptors) to single cells of the amygdala. Recordings were made in chloralosed cats from 249 cells in four subnuclei of the amygdala. Forty-six percent of cells tested responded to carotid sinus nerve stimulation and more than one-half of them responded to selective baroreceptor or chemoreceptor activation or to electrical stimulation of the locus ceruleus. Of 11 cells responding similarly (inhibition) to carotid sinus nerve stimulation and to selective baroreceptor activation, all were inhibited by locus ceruleus stimulation, also. Approximately 17% of cells tested responded to at least one exteroceptive stimulus (acoustic, optic, or tactile) whereas 14% responded to more than one exteroceptive stimulus in a similar manner. Amygdalar cells were also identified that responded to visceral (renal nerve) and somatic (iliac nerve) stimulation. Many cells received input both from enteroreceptors and from exteroceptors. These results suggest that baroreceptor input to single neurons in the amygdala is often convergent with input from the locus ceruleus. In addition, the convergence of both internal and external sensory inputs to single neurons is further evidence that the amygdala is a site for the integration of responses to arousal.

Increased Sensitivity to Arousal in Spontaneously Hypertensive Rats is Partially Dependent Upon the Amygdala

This study was designed to determine the effects of behavioral arousal on baroreflex regulation of heart rate in stroke-prone SHR (spSHR) and to ascertain whether the integrity of the amygdala is necessary to mediate these effects. Heart rate responses to phenylephrine-induced increases in arterial pressure were used as an index of baroreflex sensitivity (BRS). spSHR had reduced BRS compared to WKR. Electrical stimulation of the amygdala suppressed BRS in conscious rats only at intensities that elicited behavioral arousal. When normalized for control bradycardiac responses, the spSHR demonstrated a greater suppression of BRS upon amygdalar stimulation than Wistar-Kyoto rats (WKR). Confrontation with a mouse, used to elicit behavioral arousal, attenuated BRS in both spSHR and WKR. Ablation of the central nucleus of the amygdala and adjacent tissue prevented confrontation-induced suppression of BRS both in WKR and spSHR. These data suggest that spSHR are more sensitive to suppression of BRS due to arousal elicited by stimulation of the amygdala. Furthermore, the amygdala is necessary for arousal-induced suppression of BRS in WKR and spSHR.

Involvement of dopamine in amygdaloid kindling

The concentrations of dopamine, noradrenaline, and dihydroxyphenylacetic acid were determined in the amygdala, neostriatum, neocortex, hippocampus, brain stem, and hypothalamus of cats, which had had 9 to 14 tonic-clonic kindled seizures. No significant biochemical changes were observed compared to control cats. Pharmacological manipulations of dopamine receptors (haloperidol, apomorphine) did not modify the kindling procedure. According to the data it seems unlikely that dopamine plays a major role in amygdaloid kindling.

Baroreceptor sensitivity during desynchronized sleep

Sleep is characterized by periods of cortical and subcortical desynchronization similar to that observed during arousal. Because baroreflex control of heart rate is suppressed in the aroused state, the present study compared the cardiac index of baroreflex sensitivity in awake cats with that during desynchronized sleep to determine the level of arousal and its affect on autonomic regulation. Cats were prepared for long-term arterial pressure, cortical, and subcortical EEG and EMG recording. After acclimatization to the laboratory, cats engaged in spontaneous periods of desynchronized sleep. During this period, a bolus of angiotensin II was injected i.v. and the subsequent change in the R-R interval of the cardiac cycle was recorded during the rising phase of the pressor response. These values were compared with values obtained from the same cats during quiet and active wakefulness and those obtained during drug-induced desynchronized sleep with gamma-hydroxybutyrate. The values obtained during naturally occurring desynchronized sleep were comparable to those observed during drug-induced desynchronized sleep. In contrast, the increase in the R-R interval in awake cats, particularly quiet ones, was greater than that seen during desynchronized sleep or during active periods in the awake animal. These data suggest that there is a correlation between the level of arousal, as measured by EEG activity, and the cardiomotor component of baroreflexes.

Monoamine metabolites in the CSF of conscious unrestrained cats

The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured repeatedly over a period of up to 5 months at different sites of the brain ventricular system in unrestrained, awake cats. Samples of 10 microliter CSF were analyzed by high pressure liquid chromatography and subsequent electrochemical detection. Concentrations were in the range of 30-130 ng/ml for DOPAC, 110-340 ng/ml for 5-HIAA and 180-750 ng/ml for HVA. The monoamine metabolites were constant even over a period of several months if measured in the same animal but there was a marked interindividual variation. A marked gradient for monoamine metabolites was found when CSF samples from frontal sites of the lateral ventricle were compared to CSF samples from the dorsal lateral ventricle. The concentrations of DOPAC and HVA were higher at frontal sites.

Neurobiology of REM Sleep

As early as 1867 Wilhelm Griesinger reported on eye movements not related to vision but related to fantasies. These eye movements occurred both during the transition from wakefulness to sleep and during dreaming. From these observations he concluded that sleep was not a passive but rather an active state. It was another 86 years before Aserinsky and Kleitman (1953) discovered that sleep is not a homogeneous process but is organized in rhythmically occurring cycles of different stages, each of which is characterized by specific behavioral, electrophysiologic, autonomic, and endocrine changes. Since then, sleep was grossly divided into nonREM sleep, also called slow wave sleep (SWS), and REM sleep, also called desynchronized sleep (DS), D sleep, and paradoxical sleep (PS).