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Effects of posttraining injection of cholinergic agonists and antagonists into the amygdala on retention of passive avoidance training in rats.

Rats were given a single footshock while licking a water tube and tested 24 hr later for retention of the footshock experience. A single bilateral injection of a subseizure dose of physostigmine into the amygdala applied immediately, but not 18 hr, after the footshock imparied retention. This effect appeared to be somewhat localized, as physostigmine injected into the hippocampus or lateral ventricles did not disrupt retention. Conversely, a subseizure dose of atropine sulfate into the amygdala, given immediately or 18 hr after the footshock did not impair retention. Atropine injected concurrently with physostigmine into the same amygdaloid loci counteracted a potential physostigmine-induced retention deficit. Injection of carbachol into the amygdala also impaired retention; however, carbachol precipitated seizures and possibly exerted proactive consequences on performance. The time-dependent nature of the deficit following physostigmine is consistent with the view that injection of cholinergic agonists into the amygdala disrupts memory for the footshock experience.

Amygdala

Suppression and disinhibition of instrumental alimentary reactions after successive lesions of the dorsomedial and lateral amygdala in dogs.

Damage of the dorsomedial amygdala produced impairment of instrumental performance to CS(+) with no changes to CS(-). Subsequent lesion of the lateral amygdala resulted in restoration of instrumental performance to CS(+) and transient disinhibition to CS(-). These results support the hypothesis that the dorsomedial amygdala is involved in facilitation, while the lateral amygdala in inhibition of alimmentary reactions.

Amygdala

Histone Arginine Methylation Regulates Neuropeptide Y Expression in the Basolateral Amygdala to Promote Reward-Seeking Behaviour.

The basolateral amygdala (BLA) serves in the evaluation of reward. However, the causal molecular substrates in the BLA necessary for reward seeking behaviour are largely unknown. Reward conditioning induces long-lasting changes in epienzymes in limbic areas, including the amygdala. The current study probed the role of histone arginine methylation as a novel epigenetic mechanism in neuropeptide Y (NPY) gene regulation in the BLA during reward and reinforcement. For reward conditioning, adult Wistar rats were trained to self-administer sucrose pellets in a nose-poke operant chamber. Reward conditioning increased protein arginine methyltransferase 4 (PRMT4) and NPY in the BLA. Moreover, after operant conditioning, histone arginine methylation (H3R17me2a) and PRMT4 occupancy at the NPY promoter were heightened. PRMT4 was predominantly colocalised in the nucleus of the NPY-expressing cells in the BLA. Intra-BLA administration of specific siRNA or inhibitor of PRMT4 after conditioning waned the nose-poke activity, which was further reinstated during the subsequent 5 days. These effects of PRMT4 repression were correlated with the NPY expression and H3R17me2a levels at the NPY promoter. Furthermore, NPY peptide administration after PRMT4 siRNA or inhibitor infusion in BLA restored the nose-poke activity. PRMT4 is known to interact with CREB-binding protein (CBP). Therefore, co-occupancy of PRMT4 and CBP resulted in heightened histone acetylation (H3K14ac) in the conditioned rats. The current study suggests a pivotal role of PRMT4-mediated histone arginine methylation in NPY gene expression in the amygdala necessary for the reward-seeking behaviour.

Animals

Differential effects of basolateral amygdala lesions on behavior, corticosterone, and prolactin responses.

The present experiment examines hormone-behavior relationships following manipulation of the amygdala. Affective behavior and levels of corticosterone and prolactin were compared in rats with lesions of the basolateral amygdala and in nonlesioned and sham-operated controls. Animals with lesions of the basolateral amygdala were found to be hyperreactive and to have normal resting levels of corticosterone and prolactin but potentiated corticosterone responses to stress. Normal prolactin stress responses were unaltered by the lesion. The results are discussed in relation to behavioral and endocrine changes seen following other limbic system lesions.

Amygdala

[Role of the amygdala in the occurence of oro-alimentary signs of during epileptic seizures in man (author's transl)].

The authors study the role of amygdala dysfunction in cases of oro-alimentary signs occuring in seizures recorded during a series of stereo-electroencephalographic investigations (S.E.E.G.) carried out for neurosurgical purposes. The patients under study have an epilepsy that is resistant to drug therapy. This work concerns 89 seizures with "oro-alimentary motor activity" recorded in 59 patients with whom it was possible to establish sufficiently rigourous anatomical - electrical - clinical correlations. This study enabled us to show that : --a seizure characterized by "oro-alimentary motor" signs (with the exclusion of swallowing movements) is related to a discharge that directly involves the amygdala. --a critical discharge affecting the anterior temporal region is expressed as : oro-alimentary activity either accompanied or not by other signs (breaking contact is exceptional). --late "oro-alimentary motor activity" also indicates disorganization of the amygdala, but offers no conclusion on the origin of the discharge.

Amygdala

Interactions of amygdala lesions with effects of pilocarpine and d-amphetamine on mouse killing, feeding, and drinking in rats.

Repeated injections of 7.5 mg/kg pilocarpine induced mouse killing in both amygdala-lesioned and sham-operated rats, but more injections were required in the lesioned animals. Killing was evoked least readily in rats that showed substantial weight loss after surgery and that had damage to more medial regions of the amygdala. d-Amphetamine (.75, 1.50, or 3.00 mg/kg), administered either before or after a killing test, inhibited pilocarpine-induced killing in both surgical groups. Amygdala lesions attenuated pilocarpine-facilitated drinking in sated animals but did not alter the inhibitory effects of either pilocarpine or d-amphetamine on feeding or drinking.

Aggression

Absence of sympathetic cholinergic vasodilatation in cats during early stages of affective behaviour elicited by stimulation of central amygdala, postero-lateral hypothalamus and locus coeruleus.

1. Stimulation of the central amygdala, postero-lateral hypothalamus and locus coeruleus in cats resulted in a sustained increase in arterial pressure, an increase in heart rate, with a poststimulation bradycardia and an increase in peripheral resistance (vasoconstriction in the vessels of the hindlimbs). The behavioural pattern was characterized by an alerting reaction. Increased stimulus intensities resulted in rage reactions if the amygdala or the hypothalamus were stimulated. 2. Stimulation of the basal amygdala resulted in a cardiovascular pattern characterized by a sympathetic cholinergic vasodilatation. The concomitantly observed behaviour was characterized by alerting, anxious behaviour, eventually resulting in defence. 3. Alerting was not necessarily linked to sympathetic cholinergic vasodilatation. 4. The cardiovascular pattern including sustained vasoconstriction of the vessels of the hindlimbs was supposed to be of greater importance for the induction of hypertension than the cardiovascular pattern, including sympathetic cholinergic vasodilatation.

Affect

Dopamine evoked inhibition of single cells of the feline putamen and basolateral amygdala.

1. In cats under pentobarbitone or halothane anaesthesia, neurones of the putamen and basolateral amygdala were inhibited with a similar time course by iontophoretic applications of dopamine and gamma-aminobutyric acid (GABA), ejected with relatively short (20 sec) low intensity (less than 40 nA) pulses of positive current from five and seven barrelled extracellular micropipettes. The use of a stereotaxically positioned guide tube, sealed to the skull with dental cement, made it possible to obtain stable recording conditions and to correlate the stereotaxic position of the cells with the position of the micro-electrode tracks determined histologically by the post-mortem reconstruction of serial sections. 2. Since in cats anaesthetized with pentobarbitone none of the cells were found to be spontaneously active, the relative potency of dopamine and GABA were compared on glutamate excited cells. Approximately 2-5 times more current was required to release sufficient dopamine to cause just submaximal inhibition, equal in magnitude and duration to that evoked by GABA. 3. In nitrous oxide/halothane anaesthetized cats, approximately one quarter of the cells were spontaneously active. Relative potency studies showed that for dopamine, currents 2-0 and 1-6 times larger than those used for GABA were required to inhibit glutamate excited and spontaneously active cells respectively. 4. When the depth distribution of the cells was compared with the sensitivity of the cells to dopamine and GABA, the most sensitive cells were found to lie within the putamen and the basolateral amygdala. 5. On more than one third of the cells tested, iontophoretic application of the neuroleptic, alpha-flupenthixol of more than 3 or 4 min in duration, greatly reduced or abolished the inhibition of the cells by dopamine without impairing their sensitivity to GABA. 6. In four cats, large I.V. injections of alpha-flupenthixol (10 mg/kg) and the more potent neuroleptic pimozide (1 mg/kg) had no significant effect on the dopamine or GABA sensitivity of seventy cells in the putamen and basolateral amygdala. 7. Our results are in keeping with the view that dopamine has a predominantly inhibitory action in the mammalian forebrain. However the failure of I.V. neuroleptics to modify the sensitivity of the cells to dopamine suggests that the dramatic effects of neuroleptics on animal behaviour may not be explicable simply in terms of a generalized blockade of dopamine receptors at post-synaptic sites.

Action Potentials

ADH release from cut pituitary stalk and intact pituitary gland during amygdala stimulation at various frequencies in rats.

Changes in antidiuretic substance (i.e., vasopressin) release from the cut pituitary stalk and the intact pituitary gland were observed during electrical stimulation of amygdala medial nucleus. Electrical pulses of 4 or 36 cycles per second (cps) were used and in both cases the same energy (about 2.160 nanowatt seconds) per 1.5 sec-train of electrical pulses remained constant. Antidiuretic substance release from the hypothalamic end of the cut pituitary stalk and from the intact pituitary gland increased during the 36-cps electrical stimulation of amygdala medial nucleus, however the 4-cps electrical stimulation of this structure did not produce any changes in these processes. The results obtained indicate that the medial nucleus of amygdala is able to change the function of the hypothalamo-hypophysial system and can be motivated with high frequency stimulating pulses.

Amygdala

Studies on the puberty-controlling function of the mediocortical amygdala in the immature female rat.

The puberty-controlling function of the mediocortical amygdala in immature female rats was investigated by lesioning this region at different ages and by studying the effects on the onset of spontaneous and experimentally-induced precocious puberty. At 21 days of age, bilateral lesions in the anterior mediocortical amygdala (AMCA) caused precocious puberty and enhanced the puberty-accelerating effect of bilateral lesions produced simultaneously in the medial preoptic area (MPA). Similar lesions, ineffective on day 26, delayed the onset of puberty when produced on day 32 in otherwise untreated rats. Lesions in the posterior mediocortical amygdala (PMCA) at 26 or 32 days of age postponed puberty in untreated rats and inhibited the advancement of their 1st pubertal ovulation that resulted from damage to the ventromedial-arcuate region (VAH) or daily administration of 0.05 mug estradiol benzoate (EB) per 100 g b.w. The results confirm earlier findings of different gonadotropin-controlling activities of the AMCA and PMCA in immature female rats and suggest maturational changes in the function of both areas. The gonadotropin-inhibiting action exerted by the AMCA at 3 weeks of age is lost when puberty approaches; a gonadotropin-stimulating activity seems to develop in both the AMCA and PMCA.

Age Factors

Inhibition of ovulation in the rat by electrical stimulation of the lateral amygdala.

Effects of electrical stimulation of the lateral amygdaloid areas on ovulatory gonadotropin release were examined in adult Wistar female rats. Electrical stimulation was applied in rats in proestrus under ether anesthesia with square wave pulses of 0.5 ms duration and 100 Hz frequency for 30 min (30 sec on and off). Stimulation of the lateral amygdala blocked ovulation in 50% of animals when it was applied between 13:30 and 14:30 with a current of 300 muA. Stimulation of the medial amygdala under the same experimental condition was absolutely ineffective to block ovulation. Sham stimulation was also ineffective. In determining the gonadotropin concentration in serum, the stimulation into the lateral amygdala was observed to inhibit the ovulatory release of LH, FSH and prolactin. It may be said that the lateral amygdaloid area participates in the control of gonadotropin release in an inhibitory manner.

Amygdala

Blood supply of the rat amygdala.

The cerebral vessels of the rat were filled with inks of different colours. The topography of the vessels of the amygdala were reconstructed from serial sections. The circulation of the individual amygdaloid nuclei was studied in detail. The arteries of the amygdala arise from the deep and cortical branches of the internal carotid and middle cerebral arteries. Eight major arteries were found to supply blood to the amygdala. All amygdaloid nuclei receive branches from both arterial trunks. The vast majority of the veins are collected by the middle cerebral and basal veins. Only a small fraction drains into the hippocampal vein. Of particular importance are the veins ending in the basal vein and those cortical ones that run in the rhinal sulcus. All amygdaloid nuclei have a multidirectional drainage.

Amygdala

Spontaneous locomotor activity and food and water intake in rats with medial amygdala lesions.

Locomotor activity was studied with the method of electromagnetic activity meters, before and after operation in rats bilaterally lesioned in medial amygdala, and in a sham-operated control. Two activity tests were performed daily. In the first test spontaneous activity was recorded for a 30 min period without access to food or water. The second test measured 12 h of nocturnal activity with full access to food and water. Bilateral destruction of the medial amygdala resulted in an increase of locomotor activity in the 30 min test and a decrease in locomotor activity in the 12 h test. Postoperative decrease in food and water intake and body weight were only transient. These results point to a participation of the medial amygdala in the complex mechanism of locomotor activity and alimentary motivation.

Amygdala

Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats.

The influence of the cerebellum on activity of the septal region, hippocampus, and amygdala of cats and rats was determined by obtaining unit recordings from those supratentorial sites with cerebellar stimulation. With stimulation of the postral vermis, fastigial nucleus, and intervening midline folia of the cerebellum, units in the septal region were facilitated, whereas those in the hippocampus were inhibited. Mixed results were obtained in the amygdala, some units being facilitated and others inhibited. Stimulation over the lateral cerebellar hemispheres and dentate nucleus, on the other hand, yielded no changes in activity, and stimulation of the posterior vermis produced inconsistent septal facilitation and no hippocampal response. With stimulation of the rostral cerebellar vermis and fastigial nucleus, evoked potentials at the supratentorial sites were of very short delay times, indicating direct pathways from the cerebellum to the septal region, hippocampus, and amygdala. When the dentate and fastigial nuclei were lesioned in cats, the firing rate of cells at supratentorial sites was not affected and cerebellar vermis stimulation did not significantly alter delay times of evoked responses, providing further evidence of a direct influence of the cerebellar vermis on the supratentorial sites. Relating these findings to previous patient and animal data provides a rationale for use of specific types of cerebellar simulation in the treatment of intractable behavioral disorders and epilepsy.

Amygdala

[Multineuronal activity of the basolateral portion of the amygdala in rabbits under conditions of NaCl microinjections into the lateral preoptic field and water deprivation].

A study of the multineuronal activity of the rabbit basolateral amygdala has shown that both a microinjection of NaCl solution into the lateral preoptic field and water deprivation result in the appearance of high-amplitude spikes in the pattern of recorded activity. After microinjection these spikes proceeded with a high frequency. Consumption of water blocked this activity not immediately, but only in a day to three days under conditions of the animal's unrestrained access to water and food. The data obtained point to the arrival of information on drinking to the amygdala; they also imply the formation of certain relationships between LPF and the amygdala.

Amygdala

Commissural projection to the amygdala thourgh the fimbria fornix system in the cat.

Single shock stimulations have been applied stereotaxically and bilaterally in the region of the caudo-thalamic groove of the cat. These stimulations elicit diphasic potentials in the amygdala. Using combined methods of stimulation and lesion, it has been demonstrated that these electrical responses are due to the excitation of fibers projecting rostrally in the lateral border of the contralateral fimbria and caudally in the homologous part of the homolateral fimbria. A commissural path has been identified in the rostral part of the fimbria-fornix. Analysis of the experimental data has shown that the projection system consists of a discrete bundle of fibers which probably reaches the amygdala directly, in the dorsal part of the basal nucleus. The length of the explored portion of this pathway has been measured. The calculated conduction velocity of this amygdalopetal commissural component of the fimbria is 4.5 m/sec.

Amygdala

Partial Klüver-Bucy syndrome produced by destroying temporal neocortex or amygdala.

The temporal neocortex was removed in 4 monkeys, and 5 received amygdala destruction. Four control animals received skin and muscle incisions. The monkeys were compared on a visual pattern discrimination task, a food-non-food discrimination, and a rating scale that measured agonistic and approach behavior. Only the cortical lesion disrupted retention of the visual pattern task and neither lesion disrupted performance of the food-non-food task. Both lesions produced oral behavior, increased reaction to stimuli and decreased emotionality. Thus, the major symptoms of the Klüver-Bucy syndrome are produced by destroying either the temporal neocortex or the amygdala.

Amygdala

Facilitatory and inhibitory effects of electrochemical stimulation of the amygdala on the release of luteinizing hormone.

The effect of amygdaloid stimulation on the release of luteinizing hormone (LH) was studied in unanesthetized, unrestrained rats. Electrochemical stimulation (anodic D.C.) was applied at 11.30 h through stainless steel electrodes chronically implanted into different amygdaloid nuclei; medial (Men.), cortical (Con.), central (Cn.), or basolateral (Bln.). A plastic cannula inserted into the jugular vein was used for obtaining blood samples at different times of the experimental procedure. In rats on the day of proestrus, stimulation (100 micronA/30 sec) in the Bln. resulted in blockade of spontaneous ovulation and of the preovulatory LH release and that in the Cn. produced a delay in the hormone discharge. On the contrary, stimulation in the Men. was effective in advancing the time of the normal LH surge, while no change of the normal pattern occurred from the Con. Stimulation (100 micronA/60 sec) of ovariectomized estrogen primed rats applied in the Men. or the Con. induced LH release, while that in the Bln. or the Cn. had no effect. The release of LH by Men. stimulation and the blocking effect of Bln. showed a close relationship with the amount of current delivered. Lower thresholds were required for inhibition than for activation. The release of LH induced by stimulation in the Men. of ovariectomized estrogen primed rats occurred at the same time of the day whether the stimulus was applied at 8.30 h, 11.30 h or 14.00 h, indicating a modulatory effect of the amygdala. No changes in serum LH concentration were observed after stimulation of the Men. of castrated estrogen primed male rats or in the Bln. of ovariectomized non-primed rats. The present results indicate that the amygdala exerts a dual effect on the release of LH, the Bln. being inhibitory and the Men. and Con. facilitatory.

Amygdala