The medial amygdala: Serotonergic inhibition of shock-lnduced aggression and pain sensitivity in rats

Two aspects of the amygdaloid complex (corticomedial and basolateral) were examined with reference to serotonergic inhibition of shock-induced aggression. Fighting was significantly depressed by serotonergic stimulation (5-HT, 10 μg bilateral) in the corticomedial amygdala while serotonergic blockade (methysergide, 5 μg bilateral) in this region increased levels of fighting. No consistent effects were obtained with serotonergic manipulation of the basolateral amygdala. Further investigation revealed that the state of serotonergic activity in medial amygdaloid sites was associated with concomitant alterations in the animals' sensitivity to footshock. Results are discussed in relation to a) a general inhibitory role of serotonin in behavioural mechanisms and b) a dopaminergic-serotonergic balance for behavioural arousal involving medial amygdaloid nuclei.     

The neural basis of prolonged suppression of predatory attack. I. Naturally occurring physiological differences in the limbic systems of killer and non-killer cats

The epileptic excitability of the basolateral amygdala was found to correlate with differences in predatory and defensive predisposition of rat-killing cats and non-rat killers. The threshold for elicitation of afterdischarge (ADT) in the amygdalas of rat killers was higher than the ADTs of non-rat killers. Furthermore, non-rat killers with the lowest ADTs had the weakest attack tendencies and were most sensitive to a variety of environmental threats in addition to those posed by prey. These differences in excitability were not found in control areas lateral to the amygdala or in the ventral hippocampus. The possibility that ADT is a behaviorally relevant measure of a long-term predatory suppression function of the amygdala is discussed.     

Food-deprivation-induced behavioral arousal: mediation by hypothalamus and amygdala.

Electrolytic lesions of the basomedial hypothalamus eliminated food-deprivation-induced stabilimeter activity in rats that were prevented from becoming obese. Knife cuts lateral to the basomedial area (separating the medial and lateral hypothalamus) potentiated this activity, as did transections posterior to the basomedial region. Anterior transections (between anterior and medial hypothalamus), however, eliminated the effect. Lesions of the stria terminalis and amygdala likewise abolished deprivation-induced locomotor activity, but elevated ab-lib activity to a level comparable with that after deprivation in intact animals. Animals with combined basomedial-stria terminalis lesions behaved like animals with basomedial lesions. These results suggest that food-deprivation-induced locomotor activity in stabilimeter cages is due to a disinhibition of the basomedial hypothalamus by the amygdala via the stria terminalis.     

Gabaergic mechanisms of hypothalamic nuclei in the expression of conditioned fear

The amygdala, the dorsal periaqueductal gray (dPAG), and the medial hypothalamus have long been recognized to be a neural system responsible for the generation and elaboration of unconditioned fear in the brain. It is also well known that this neural substrate is under a tonic inhibitory control exerted by GABA mechanisms. However, whereas there is a growing body of evidence to suggest that the amygdala and dPAG are also able to integrate conditioned fear, it is still unclear, however, how the distinct hypothalamic nuclei participate in fear conditioning. In this work we aimed to examine the extent to which the gabaergic mechanisms of this brain region are involved in conditioned fear using the fear-potentiated startle (FPS). Muscimol, a GABA-A receptor agonist, and semicarbazide, an inhibitor of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD), were used as an enhancer and inhibitor of the GABA mechanisms, respectively. Muscimol and semicarbazide were injected into the anterior hypothalamus (AHN), the dorsomedial part of the ventromedial nucleus (VMHDM), the dorsomedial (DMH) or the dorsal premammillary (PMD) nuclei of male Wistar rats before test sessions of the fear conditioning paradigm. The injections into the DMH and PMD did not produce any significant effects on FPS. On the other hand, muscimol injections into the AHN and VMHDM caused significant reduction in FPS. These results indicate that injections of muscimol and semicarbazide into the DMH and PMD fail to change the FPS, whereas the enhancement of the GABA transmission in the AHN and VMHDM produces a reduction of the conditioned fear responses. On the other hand, the inhibition of this transmission led to an increase of this conditioned response in the AHN. Thus, whereas DMH and PMD are known to be part of the caudal-most region of the medial hypothalamic defensive system, which integrates unconditioned fear, systems mediating conditioned fear select the AHN and VMHDM nuclei that belong to the rostral-most portion of the hypothalamic defense area. Thus, distinct subsets of neurons in the hypothalamus could mediate different aspects of the defensive responses.     

Differential involvement of the central amygdala in appetitive versus aversive learning

Understanding the function of the distinct amygdaloid nuclei in learning comprises a major challenge. In the two studies described herein, we used c-Fos immunolabeling to compare the engagement of various nuclei of the amygdala in appetitive and aversive instrumental training procedures. In the first experiment, rats that had already acquired a bar-pressing response to a partial food reinforcement were further trained to learn that an acoustic stimulus signaled either continuous food reinforcement (appetitive training) or a footshock (aversive training). The first training session of the presentation of the acoustic stimulus resulted in significant increases of c-Fos immunolabeling throughout the amygdala; however, the pattern of activation of the nuclei of the amygdala differed according to the valence of motivation. The medial part of the central amygdala (CE) responded, surprisingly, to the appetitive conditioning selectively. The second experiment was designed to extend the aversive versus appetitive conditioning to mice, trained either for place preference or place avoidance in an automated learning system (INTELLICAGE). Again, much more intense c-Fos expression was observed in the medial part of the CE after the appetitive training as compared to the aversive training. These data, obtained in two species and by means of novel experimental approaches balancing appetitive versus aversive conditioning, support the hypothesis that the central nucleus of the amygdala is particularly involved in appetitively motivated learning processes.     

Basolateral amygdala inactivation impairs learned (but not innate) fear response in rats

Numerous studies have suggested that the amygdala is involved in the formation of aversive memories, but the possibility that this structure is merely related to any kind of fear sensation or response could not be ruled out in previous studies. The present study investigated the effects of bilateral inactivation of the amygdaloid complex in rats tested in the plus-maze discriminative avoidance task. This task concomitantly evaluates aversive memory (by discrimination of the two enclosed arms) and innate fear (by open-arm exploration). Wistar rats (3-5 months-old) were implanted with bilateral guide cannulae into basolateral amygdala. After surgery, all subjects were given 1 week to recover before behavioral experiments. Afterwards, in experiment 1, 15 min prior to training, 0.5 μl of saline or muscimol (1 mg/ml) was infused in each side via microinjection needles. In experiment 2 the animals received injections immediately after the training session and in experiment 3 rats were injected prior to testing session (24 h after training). The main results showed that (1) pre-training muscimol prevented memory retention (evaluated by aversive arm exploration in the test session), but did not alter innate fear (evaluated by percent time in open arms); (2) post-training muscimol impaired consolidation, inducing increased percent in aversive arm exploration in the test session and (3) pre-testing muscimol did not affect retrieval (evaluated by aversive enclosed arm exploration in the test session). The results suggest that amygdala inactivation specifically modulated the learning of the aversive task, excluding a possible secondary effect of amygdala inactivation on general fear responses. Additionally, our data corroborate the hypothesis that basolateral amygdala is not the specific site of storage of aversive memories, since retention of the previously learned task was not affected by pre-testing inactivation.     

Shock-induced aggression and pain sensitivity in the rat: Catecholamine involvement in the corticomedial amygdala

The possible role of amygdaloid catecholamines in the control of shock-induced aggression and pain sensitivity in the rat was investigated. Bilateral microinjections of chlorpromazine into the corticomedial amygdala resulted in decreased fighting and decreased sensitivity to the shock stimulus. Further analysis of this effect, using specific adrenergic antagonists, revealed that neither a- nor Padrenergic systems appeared to be responsible for the behavioral effect of chlorpromazine. Injections of haloperidol into the same region, however, yielded a reduction similar to that produced by chlorpromazine, while dopamine injections resulted in significant elevations in both fighting and pain sensitivity. No effect on any of these behavioral measures was obtained following injection of any of the agents into the basolateral amygdala. These results suggest that the observed effect of catecholamine injections in the corticomedial amygdala is related to changes in pain sensitivity mediated by dopamine.     

Conditioned and unconditioned fear organized in the periaqueductal gray are differentially sensitive to injections of muscimol into amygdaloid nuclei

The lateral and basolateral nuclei of the amygdala (LaA and BLA, respectively) serve as a filter for unconditioned and conditioned aversive information that ascends to higher structures from the brainstem, whereas the central nucleus of the amygdala (CeA) is considered to be the main output for the defense reaction. It has been shown that the dorsal periaqueductal gray (dPAG) is activated by threatening stimuli and has important functional links with the amygdala through two-way anatomical connections. In this work, we examined the influence of chemical inactivation of these nuclei of amygdala on the freezing and escape responses induced by electrical stimulation through electrodes implanted in the dPAG of Wistar rats. Each rat also bore a cannula implanted in the LaA, BLA or CeA for injections of muscimol (0.5 microg/0.5 microL) or its vehicle. The duration of freezing behavior that outlasts electrical stimulation of the dPAG was also measured. On the following day, these animals were submitted to a contextual fear-conditioning using foot shocks as unconditioned stimulus. Conditioned freezing to contextual cues previously associated with foot shocks was also inhibited by injections of muscimol into these amygdaloid nuclei. The contextual conditioned freezing behavior is generated in the neural circuits of conditioned fear in the amygdala. The data obtained also show that injections of muscimol into the three amygdaloid nuclei did not change the aversive threshold of freezing, but disrupted the dPAG post-stimulation freezing. Previous findings that the latter freezing results directly from dPAG stimulation and that it is not sensitive to a context shift suggest that it is unconditioned in nature. Thus, the amygdala can affect some, but not all, aspects of unconditioned freezing. Post-stimulation freezing may reflect the process of transferring aversive information from dPAG to higher brain structures.     

Defensive behaviors in rats following septal and septal--amygdala lesions

Rats with anterior septal lesions showed a pattern of consistent enhancement of defensive behaviors normally elicited by threatening conspecifics, with no enhancement of attack or general reactivity. Further division of this group indicated that damage to sites anterior and ventral to the septal area, sites previously implicated in the "septal syndrome," produces maximal effect on these behaviors. When amygdala lesions are combined with septal damage this enhanced defensive responding is almost completely eliminated. These results were interpreted as indicating that the septal syndrome represents hyperdefensiveness to conspecific threat stimuli rather than aggression or increased general reactivity, and that amygdaloid mechanisms are also involved in the regulation of conspecific defensive behaviors.     

中等强度情绪性图片的神经机制——一项fMRI研究

采用修订后的中等唤起度的国际情绪图片为刺激材料,以12名女性大学生为被试,考察情绪性图片引起的脑激活模式。结果发现,与中性条件相比,消极情绪图片激活了枕叶、杏仁核、海马旁回和壳核。积极情绪图片引起枕叶、内侧眶额、额中回等脑区的激活,研究结果再次验证了杏仁核与消极情绪的密切关系,同时推测,内侧眶额可能是中等唤起度的趋近性积极情绪的一个脑功能区。     

Involvement of amygdala in inhibitory control over aggression in the rat: A synopsis

An experimentally produced hyperreactivity facilitates initiation of mouse-killing in rats that did not previously develop any stable inhibition of interspecific aggression. Destruction of the corticomedial amygdala or interruption of the stria terminalis interferes with the development of such an inhibition on the basis of “social” influences, whereas lateral amygdaloid lesions have no effect on mouse-killing.     

The role of the amygdala in emotional experience during retrieval of personal memories

ABSTRACT

Although the role of the amygdala in emotional memory retrieval has long been established, how such engagement varies depending on valence and retrieval context is less clearly understood. Participants retrieved personal memories associated with primarily positive, primarily negative, and mixed-valence images, pressing a button when successful. The button press divided trials into search and elaboration phases. Participants provided positivity and negativity ratings immediately following each trial, and then again in a post-retrieval survey. The relation between amygdala recruitment and emotionality exhibited a four-way interaction, with no other significant main effects or interactions. The interaction was driven by a temporal shift in the role of amygdala recruitment during retrieval of memories associated with mixed-valence images: Negativity ratings were supported more by search-related activity whereas positivity was more strongly associated with elaboration. Amygdala activity during retrieval relates to emotional experience in more complicated ways than previously understood. When participants were able to consider positive and negative aspects of the same event, amygdala recruitment during search and elaboration were associated with opposite behavioural effects. Such findings suggest that the amygdala may support distinct aspects of emotional experience for the same memory depending on when during retrieval it is recruited.     

Group rearing abolishes hyperdefensiveness induced in weanling rats by lateral septal or medial accumbens lesions but not by medial hypothalamic lesions

Lesions of the medial hypothalamus, medial accumbens, or septum were made in 21- to 25-day-old male hooded rats. Half of the animals in each group were subsequently reared in groups and the other half in isolation. When tested for defensiveness toward the experimenter at 31, 34, and 37 days postoperatively, rats with medial hypothalamic lesions were most hyperdefensive toward the experimenter if reared in isolation but were significantly more defensive than sham-lesioned animals even when reared in groups. Rats with septal lesions were significantly more defensive than sham-lesioned animals only when reared in isolation while rats with medial accumbens lesions were not different from controls whether reared individually or in groups. These results suggest that the medial hypothalamus may have a special importance in determining temperament since the hyperdefensiveness that results from interference with its functioning is resistant to experiential remediation.     

Organization of the amygdala with special reference to various pathological syndromes

Our understanding of the functional organization of the amygdaloid complex has considerably increased in the last 10 years. Thus the abundance of previously unsuspected neocortical and thalamic afferents to the amygdala as well as the direct projections from the central amygdala to pontine structures involved in the coordination of autonomic and motor functions, present a challenge to the previous view that the function of the complex is largely related to that better known of the hypothalamus. In this context the possible significance of the abundant opoid systems in the central amygdala will be discussed with special reference to the morphine withdrawal syndrome. The role of the amygdala in the manifestation of limbic motor signs during seizures will be reevaluated in this context.     

Chronic nicotine exposure induces a long-lasting and pathway-specific facilitation of LTP in the amygdala

Nicotine, in the form of tobacco, is the most commonly used drug of abuse. In addition to its rewarding properties, nicotine also affects many cognitive and emotional processes that involve several brain regions, including hippocampus and amygdala. Long-term changes in synaptic strength in these brain regions after drug exposure may be importantly correlated with behavioral changes induced by nicotine. Here, we study the effect of chronic oral administration of nicotine on the long-term synaptic potentiation in the amygdala, a key structure for emotional memory. We find that oral administration of nicotine for 7 d produces a significant enhancement of LTP in the amygdala. This facilitation is pathway specific: Nicotine selectively facilitates LTP in the cortical-lateral amygdala pathway, but not the thalamic-lateral and the lateral-basolateral synaptic pathway. The synaptic facilitation induced by a 7-d exposure to nicotine is long-lasting, it persists for 72 h after cessation of nicotine but decays 8 d after its cessation. In contrast, a shorter exposure of nicotine (24 h) induces only a short-lasting facilitation of synaptic plasticity that dissipates 24 and 72 h after cessation of nicotine. The facilitation of LTP in the amygdala after exposure to nicotine is mediated by removal of GABAergic inhibition, is dependent on the activation NMDA receptors, and can be prevented by blocking either α7 or β2 nACh receptors. Our results indicate that chronic exposure to nicotine can promote the induction of long-lasting modifications of synapses in a specific pathway in the amygdala.These changes in synaptic plasticity may contribute to the complex neural adaptations and behaviors caused by nicotine.     

催产素影响恐惧习得和消退的认知神经机制

恐惧是一种基本的情绪, 在人类的生存和适应中发挥着重要作用。先前的研究表明, 杏仁核、背侧前扣带回、脑岛等脑区是条件化恐惧习得的认知神经基础, 杏仁核、海马和腹内侧前额叶等脑区在恐惧消退过程中发挥重要作用。研究发现, 催产素与恐惧习得和恐惧消退过程密切相关。恐惧习得过程中, 催产素影响杏仁核、背侧前扣带回的活动, 影响杏仁核与背侧前扣带回和脑干间的功能连接, 促进或抑制恐惧习得过程; 恐惧消退过程中, 催产素影响了杏仁核和腹内侧前额叶的活动, 并且影响杏仁核与内侧前额叶和海马间的功能连接, 促进或抑制恐惧消退过程。未来研究应从性别差异、神经网络模型、身心发育和病理研究等角度展开, 力图深入理解催产素影响恐惧情绪加工的认知神经机制。     

Ventral and dorsolateral regions of the midbrain periaqueductal gray (PAG) control different stages of defensive behavior: Dorsolateral PAG lesions enhance the defensive freezing produced by massed and immediate shock

Rats that receive nociceptive electric shock in an environment normally show the conditional fear-induced defensive response of freezing when returned to that environment. If several electric shocks are given in a massed manner they will condition less freezing than the same shocks given in a distributed manner. If a single shock is given immediately after placement in the chamber it does not support any conditioning, although the same shock given after a brief delay does. Electrolytic lesions of the dorsolateral periaqueductal gray (PAG), which damaged dorsomedial, dorsolateral, and lateral PAG, enhanced freezing under these conditions. Lesions of the ventral PAG, which caused extensive damage to the central gray below the aqueduct, reduced conditioning under the more optimal parameters (distributed or delayed shock). This was taken to indicate that both of these regions support different modes of defensive behavior and that when activated, the dorsolateral PAG inbits conditional fear-induced defensive behavior. © 1995 Wiley-Liss, Inc.     

Verbal and Nonverbal Emotional Memory Following Unilateral Amygdala Damage

The amygdala is involved in the normal facilitation of memory by emotion, but the separate contributions of the left and right amygdala to memory for verbal or nonverbal emotional material have not been investigated. Fourteen patients with damage to the medial temporal lobe including the amygdala (seven left, seven right), 18 brain-damaged, and 36 normal controls were exposed to emotional and neutral pictures accompanied by verbal narratives. Memory for both narratives and pictures was assessed with a free recall test 24 h later. Subjects with left amygdala damage failed to show the normally robust enhancement of memory for verbal and nonverbal emotional stimuli. The group with right amygdala damage showed the normal pattern of facilitation of memory by emotion for both verbal and nonverbal stimuli despite an overall reduction in memory performance. Furthermore, subjects with left amygdala damage were disproportionately impaired on memory for emotional narratives as compared with memory for emotional pictures. The latter finding offers partial support for a lateralized and material-specific pattern of the amygdala's contribution to emotional memory.     

Effects of systemic glucose injection on the development of amygdala kindling in rats.

The effects of systemic glucose administration on the development of electric amygdaloid kindling seizures were examined in Wistar rats. Daily intraperitoneal injections of glucose 100 mg/kg, 20 min prior to each amygdaloid stimulation did affect the rate of kindling development in comparison with the saline-injected group. The number of stimulations required to reach stage 5 was lower in animals treated with glucose. The facilitation of kindling development found in glucose-treated rats is related to a specific decrease in the number of stimulations needed to evolve from stage 2 to stage 3. These results indicate that systemic glucose administration facilitates amygdaloid kindling in rats.     

情绪加工中杏仁核的效价特异性

杏仁核是情绪信息加工的关键脑区。近年来心理学和神经科学领域发现了杏仁核情绪加工的效价特异性现象,并且整体存在左侧杏仁核对正性情绪、右侧杏仁核对负性情绪以及双侧杏仁核负性偏好的特异性趋势,且受到材料突出特征、个体差异、任务条件的调节。未来可进一步探索注意对杏仁核情绪效价特异性的调节作用,探究动态情绪刺激加工时杏仁核的活动特点,考察心理障碍患者加工负性情绪时的杏仁核激活模式,并确定杏仁核的效价特异性在思维、计划、决策等高级认知过程中的表现。