Amygdaloid Stimulation Research Articles

Morphine enhances amygdaloid seizures and increases inter-ictal spike frequency in kindled rats

Generalized seizures were obtained in rats by daily electrical stimulation of the baso-lateral amygdala (kindling). In kindled rats, morphine i.p. injections enhanced the epileptic seizures induced by amygdaloid stimulation and increased the inter-ictal spike frequency present in the amygdaloid electroencephalography. Both effects were stereospecific and reversed by naloxone.

A factor analysis of data from 10 phases of sequential alternation of amygdaloid stimulation within the kindling paradigm

Data from a number of sequential alternation experiments were factor analyzed to determine the number of common factors present. Three dependent variables (latency of convulsion, number of trials to six convulsions, duration of convulsions) were evaluated by three procedures: principal components solution with 1s in main diagonals, principal axes solution with largest r in the diagonals, principal axes solution with R2 in the diagonals. The results were similar; the presence of two factors was suggested in the latency and criterion measures (primary site stimulation and secondary site stimulation) and one in the duration data. A principal components factor analysis over the three dependent variables showed the presence of three factors, those observed in each of the separate analyses.

The oscillation effect at near-threshold intensities during sequential alternation of unilateral amygdaloid stimulation

Previous research had indicated that an oscillation effect resulted during sequential alternation of unilateral amygdaloid stimulation with consistently low latency values for one side and consistently high values for the contralateral one. The effect of intensities approximately 15 microA above threshold was investigated in this study. The oscillation tendency occurred at these near-threshold intensities both for rats which previously had shown oscillation patterns at different intensities and for those which were being stimulated for the first time.

Effects of cycloheximide on experimental epilepsy induced by daily amygdaloid stimulation in rabbits.

Daily electrical stimulation of the amygdala caused a progressive change in electrographic afterdischarge and behavioral responses that ultimately resulted in generalized convulsions (kindling). Cycloheximide blocked the completion of kindling when administered 4 hours prior to daily electrical stimulations of the amygdala, but exerted no effect when administered shortly before the stimulation. The temporal relation between administration of cycloheximide and stimulation of the amygdala revealed that the blockade of kindling by cycloheximide was due to the suppression of focal afterdischarge rather than to the persistent inhibition of cerebral protein synthesis during the interstimulus periods.

Postseizure inhibition of kindled seizures

Rats were kindled until each periodic, bipolar, amygdaloid stimulation reliably elicited and afterdischarge and a generalized motor seizure. The inhibitory effects of one amygdaloid stimulation (antecedent stimulation) on the afterdischarges and motor seizures typically produced by the next (test stimulation) were studied in a series of experiments. Levels of antecedent stimulation which themselves elicited afterdischarges and motor seizures produced marked inhibitory effects which dissipated in approximately 90 min, whereas levels of antecedent stimulation which elicited local afterdischarges but no motor seizures had only mild inhibitory consequences. Regardless of their intensity, stimulations which evoked no epileptic responses themselves did not inhibit the responses to subsequent test stimulations. The inhibitory effect of a series of antecedent stimulations was more complex than that produced by a single stimulation. A series of 19 kindled motor seizures was elicited by amygdaloid stimulations applied at 1.5-h intervals without any indication of inhibitory effects; however, the next day the response to a single amygdaloid stimulation was almost completely suppressed. This marked inhibitory effect dissipated gradually during the next 5 days.

The oscillation effect during sequential alternation of amygdaloid stimulation with aged rats

In two experiments, aged rats (approximately 420-475 days of age) were subjected to stimulation of each amygdala in an alternating sequence. Their behavioral response to this stimulation was similar to that found previously with younger rats, systematically going from normal exploration, to automatic behavior, to clonic convulsions. They also showed the “oscillation effect,” i.e., low values in latency when stimulated on one side and high values when stimulated on the opposite side.

Retrieval of delayed evoked potentials after amygdaloid stimulation

The effect of amygdaloid stimulation on retrieval of delayed evoked potentials recorded in the cortex, mesencephalic reticular formation, lateral geniculate body, and hippocampus was investigated in unanesthetized curarized cats. Delayed evoked potentials were produced to 10–400 combinations of flashes and hypothalamic stimulation and consisted of potentials arising in response to a conditioned stimulus after a delay equal to the interval between it and the unconditioned stimulus. Amygdaloid stimulation facilitated the retrieval of these potentials if they had first been extinguished or had not appeared during initial testing.

The effect of intensity during sequential alternation of unilateral amygdaloid stimulation

Previous research indicated that an oscillation effect resulted during sequential alternation of unilateral amygdaloid stimulation, with consistent low-latency values in one side and consistent high values in the contralateral side. The effect of intensity (100, 280, 560 microA) was investigated in this study. The oscillation tendency was similar to that in previous research with 100- and 280-microA intensities. However, 560-microA intensity tended to disrupt the oscillation tendency moderately.

The effect of varying rest intervals following the development of oscillation during unilateral amygdaloid stimulation

Fifteen rats showing prominent oscillation patterns in latency during sequential alternation of unilateral amygdaloid stimulation were separated into three groups of five rats each. Group 1 rats were rested for 1 month prior to continuing sequential alternations. Groups 2 and 3 rats were rested for 3 months and 6 months, respectively. In spite of these rest intervals, most rats continued to show the same oscillation pattern as that before the rest period.

Long-lasting depression of hippocampus-mammillary body evoked potentials following stimulation of the basal amygdala in cats

Hippocampus-mammillary body evoked potentials were recorded in awake, unrestrained cats. Electrical stimulation of the basal amygdala with intensities eliciting behavioral reactions depressed the amplitude of the evoked responses. This effect, shown in 31 experiments, lasted for 20 min up to more than 4 hr. The induction of epileptic seizures ( n = 5) due to amygdaloid stimulation did not modify the duration of this depression. The effect was specific for the basal amygdala, because stimulation of central amygdala and mesencephalic reticular formation did not alter the hippocampus-mammillary body evoked potentials. Lesions within both basal and central amygdala had no constant effect on the hippocampus-mammillary body evoked potentials. The mechanism underlying the suppression of the hippocampus-mammillary body evoked potentials due to electrical stimulation of the basal amygdala is not dependent on paroxysmal activity within hippocampus and mammillary body, as was shown by depth recordings. It is speculated that this mechanism might have a protective function in the propagation of ictal discharges originating within the hippocampus.

Effects of septal lesions on behavior elicited by stimulation of the amygdaloid complex

Effects of unilateral electrical stimulation of the amygdaloid complex were observed in rats with septal lesions in two states: (a) in the acute state of increased emotionality associated with these lesions; (b) after recovery from increased emotionality. The appearance of stimulus induced emotional responses and autonomic-convulsive responses were compared to sham operates and cortically lesioned controls. In animals with septal lesions, it was found that in the acute state, there was a suppression of convulsive behavior, as compared to controls and to animals with septal lesions recovered from increased emotionality. The results indicate incompatibility of convulsive behavior induced by amygdaloid stimulation and emotional responsivity elicited by the same stimulation and by septal destruction. The relation between these findings and earlier studies dealing with anatomical connections of the amygdala is discussed.

The effects of taurine on various stages of the kindling process: A summary of results

Five experiments were conducted in which taurine was administered to rats at various stages in the kindling process. Amygdaloid stimulation was at 100-microA intensity for 30 sec. Experiments 1, 2, and 3 evaluated the effects of taurine on rats at the clonic convulsion stage with various dosages (50, 100, 200, and 400 mg/kg weight). Experiments 4 and 5 were concerned with rats at the exploration and behavioral automatism stages (dosages: 50, 100, and 200 mg/kg weight). Rats at the initial stage (normal exploration) which received taurine intraperitoneally reached the convulsion stage later than did rats injected with physiological saline. Taurine administration had no effect when rats were at the behavioral automatism or clonic convulsion stage. A second set of four experiments were conducted which used 50, 100, and 200 mg/kg dosages and the duration of stimulation was just above latency threshold. The results were similar to the first set; however, the retardation with rats at Stage 1 was not as pronounced.

The effect of bilateral stimulation during sequential alternation of unilateral amygdaloid stimulation

In two experiments, rats were subjected to a sequence of stimulations alternating from one amygdala to the contralateral one. Each phase of stimulation was for six convulsions prior to alternation to the other side. Rats In Experiment 1 had a series of six or seven phases of alternation, followed by five phases of bilateral stimulation, and concluded with seven phases of unilateral stimulation. In Experiment 2, rats had five phases of bilateral stimulation prior to seven phases of unilateral stimulation. The bilateral phases produced a modest disruption of the oscillation tendency when it was interspersed between two series of unilateral stimulation phases, more so in the criterion measure than in latency data. The effect was less on the oscillation tendency when bilateral stimulation preceded unilateral stimulation phases.

The effect of number of trials per day during sequential alternation of unilateral amygdaloid stimulation

Three groups of rats were subjected to a sequence of stimulations alternating from one amygdala to the contralateral one. Each phase of stimulation was for six convulsions prior to stimulation of the opposite side. Rats in Group 1 were stimulated six times per day; Group 2 rats had three trials each day; and one stimulation each day was provided for Group 3 rats. The oscillation tendency (high values for one side, low values for other side) was prominent with all groups but seemed most prevalent with Group 3 rats.

Spontaneous recurrent seizure state induced by daily electric amygdaloid stimulation in Senegalese baboons (Papio papio).

Daily electrical stimulation of the amygdala in Senegalese baboons (Papio papio) resulted in the development of generalized convulsive seizures focal onset through five distinct clinical stages in an average of 72 days. The chronologic pattern of electroclinical features suggested that vertical intrahemispheric ictal dissemination was of primary importance in the progressive seizure development. Some animals developed spontaneous recurrence of both partial complex and primary generalized seizures. The kindling preparation in P. papio represents a unique model of human epilepsy with its secondary generalized convulsive seizure development, spontaneously recurrent partial and primary generalized seizures in the background of predisposed epileptogenic susceptibility.

Cerebellar contributions to the papez circuit

Cerebellar influences on the various substructures in the Papez Circuit are indicated by the following. 1. Anatomical studies indicate that the major midbrain areas to which this circuit projects are : 1) ventral tegmental area; 2) interpeduncular area; and 3) periaqueductal gray areas; and these same areas project back to the limbic system. There are projections to these regions from the cerebellar nuclei, as indicated by terminal degeneration studies which show that cerebellar nuclei connect, mostly by fine fibers, with a continuum of cells located on either side of the midline in the ventral tegmentum of the midbrain. Observations that the cerebellum also projects to the locus ceruleus (NA system) and VTA (DA system) indicate that cerebellar influences can also reach the limbic areas via the catecholamine fiber bundles. 2. Electrophysiological studies indicate that vermiam and fastigial stimulation induce evoked responses in the basolateral amygdala, the hippocampus, and the septum, with latencies to the peak of first wave ranging from 4 to 8 msec and to the second wave of 16-29 msec. Citations from the physiological literature indicate that electrical stimulation of the cerebellum, especially the vermis, can modify a wide range of responses which involve functional activities of either the sympathetic or parasympathetic nervous systems. 3. Studies on electrically induced afterdischarges in the septum, hippocampus, and amygdala indicate that cerebellar stimulation can shorten the duration of or terminate the afterdischarges, and the site of lowest threshold is the midline cortex. Focal cooling of the vermis promotes prolongation of the afterdischarges as does pretreatment of animals with 6-OH dopamine. Chemical lesions in the catecholamine system induced by 6-OH dopamine reduce the effectiveness of the cerebellar stimulation, as do lesions of nucleus fastigii. These data are interpreted to indicate that the cerebellum can exert a tonic suppressor (inhibitory?) influence on substructures within the Papez Circuit. 4. Citations from animal behavioral studies indicate that electrical stimulation of the anterior cerebellum can induce responses such as arousal, predatory attack, and feeding which mimic those obtained by amygdaloid stimulation. Fastigial stimulation can produce drowsiness and EEG changes which resemble the sleep patterns resulting from stimulation of the ventral amygdala.

Posttrial hippocampal, amygdaloid, and lateral hypothalamic electrical stimulation: effects on short- and long-term memory of an appetitive experience.

Water-deprived rats were given 150 licks of a 10% sucrose solution, followed 4 sec later by 30 sec of low-intensity electrical brain stimulation applied through bipolar electrodes implanted bilaterally in the dorsal hippocampus, amygdala, or lateral hypothalamus. Retention of the licking experience was then tested either 90 sec or 24 hr after the 150-lick experience by measuring the number of licks taken on an empty drinking tube. Rats that received hippocampal stimulation licked the empty tube less than controls did during the 24-hr, but not during the 90-sec, retention test. These data suggest that the hippocampus may be critically involved in processes (e.g., consolidation) mediating long-term, but not short-term, memory. Compared with controls, rats that received amygdala stimulation did not exhibit any changes in licking at either retention test. Rats that received lateral hypothalamic stimulation showed more licking compared with controls during the 90-sec, but not the 24-hr, retention test. Subsequent tests suggested that facilitation of short-term memory may have been influenced by stimulation-induced motivational changes.

Sleep, subcortical stimulation and kindling in the cat.

A longitudinal study of the effects of sleep on amygdaloid kindling showed that kindling disrupted normal sleep patterns by reducing REM sleep and increasing awake time. Few interictal spike discharges were observed during the awake stage, while a marked increase in discharge was observed during the light and deep sleep stages. No discharges were observed during REM sleep. During the immediate post-stimulation period the nonstimulated amygdala showed a much higher rate of spike discharge. On the other hand, there was an increase in spike discharge in the stimulated amygdala during natural sleep without preceding amygdaloid stimulation. Amygdaloid stimulation at the generalized seizure threshold during each sleep stage resulted in a generalized convulsion. The influence of subcortical electrical stimulation on kindled amygdaloid convulsions was investigated in a second experiment. Stimulation of the centre median and the caudate nucleus was without effect on kindled convulsions, while stimulation of the mesencephalic reticular formation at high frequency (300 Hz) reduced the latency of onset of kindled generalized convulsions. Stimulation of the nucleus ventralis lateralis of the thalamus at low frequency (10 Hz) prolonged the convulsion latency, and at high current levels blocked the induced convulsion. Stimulation in the central gray matter at low frequency (10 Hz) also blocked kindled amygdaloid convulsions.

Amygdala and masseteric reflex. I. Facilitation, inhibition and diphasic modifications of the reflex, induced by localized amygdaloid stimulation

The changes in amplitude of the monosynaptic masseteric reflex (MR), induced by stimulation of the amygdaloid area for the defence reaction (N. basalis, pars magnocellularis) and in other subdivisions of the amygdaloid complex, were studied in cats with spinal section maintained under Flaxedil. Simultaneously, the effects of stimulation on the tonic activity of the masseteric nerve were observed. A maintained facilitation of the MR was elicited by stimulation of the lateral nucleus, the parvocellular portion of the basal nucleus and the cortical nucleus, while the reflex was inhibited during stimulation of the medial-most portion of the posterior amygdala. Diphasic changes of the MR amplitude (initial facilitation followed by delayed inhibition) were regularly observed when stimulating the magnocellular portion of the basal nucleus. These diphasic changes were closely correlated with the previously described diphasic respiratory and cardiac responses elicited from the same area (Bonvallet and Gary Bobo 1972). The initial facilitation probably corresponds to the “alerting” stage of the defence reaction and the delayed inhibition, associated with cortical, respiratory and cardiac activation, to the “defensive” stage of the reaction. Stimulation of the same area also provokes tonic or rhythmical discharges of the masseteric motoneurons which frequently occur during the delayed inhibition of the MR. The main efferent pathway mediating these motor effects is probably the ansa lenticularis.

A direct input from amygdaloid complex to caudate nucleus of the rat

Spontaneous unit activity was recorded from the caudate nucleus in rats anesthetized with urethane. Amygdaloid nucleus stimulation altered the spontaneous activity of 51 units (65% of the population tested); 23 units (29%) showed an increase and 28 (36%) a decrease of discharge rate. Moreover, 25 units (32%) responded to stimulation with stimulus-locked spikes. Post-stimulus time histograms revealed 7 patterns of response to amygdaloid stimulation. In 4 groups of cells, stimulus-locked spikes occurred followed by alteration of spontaneous discharge rate. In another 2 groups there was a change of spontaneous discharge without stimulus-locked spikes and in the final group no effect occurred. The possibility of mono-, oligo-, and polysynaptic connections from amygdaloid nuclear complex to caudate nucleus was discussed. It was suggested that an amygdalofugal connection to basal ganglia may provide a pathway whereby activity of the limbic system may exert a modulatory influence on somatic motor mechanisms.