Amygdala In Processing Research Articles

The lateral amygdala processes the value of conditioned and unconditioned aversive stimuli

The amygdala is critical for acquiring and expressing conditioned fear responses elicited by sensory stimuli that predict future punishment, but there is conflicting evidence about whether the amygdala is necessary for perceiving the aversive qualities of painful or noxious stimuli that inflict primary punishment. To investigate this question, rats were fear conditioned by pairing a sequence of auditory pips (the conditioned stimulus, or CS) with a brief train of shocks to one eyelid (the unconditioned stimulus, or US). Conditioned responding to the CS was assessed by measuring freezing responses during a test session conducted 24 h after training, and unconditioned responding to the US was assessed by measuring head movements evoked by the eyelid shocks during training. We found that pre-training electrolytic lesions of the amygdala’s lateral (LA) nucleus blocked acquisition of conditioned freezing to the CS, and also significantly attenuated unconditioned head movements evoked by the US. Similarly, bilateral inactivation of the amygdala with the GABA-A agonist muscimol impaired acquisition of CS-evoked freezing, and also attenuated US-evoked responses during training. However, when amygdala synaptic plasticity was blocked by infusion of the NR2B receptor antagonist ifenprodil, acquisition of conditioned freezing was impaired but shock reactivity was unaffected. These findings indicate that neural activity within the amygdala is important for both predicting and perceiving the aversive qualities of noxious stimuli, and that synaptic plasticity within LA is the mechanism by which the CS becomes associated with the US during fear conditioning.

The amygdala processes the emotional significance of facial expressions: an fMRI investigation using the interaction between expression and face direction

Neuroimaging studies have shown activity in the amygdala in response to facial expressions of emotion, but the specific role of the amygdala remains unknown. We hypothesized that the amygdala is involved in emotional but not basic sensory processing for facial expressions. To test this hypothesis, we manipulated the face directions of emotional expressions in the unilateral visual fields; this manipulation made it possible to alter the emotional significance of the facial expression for the observer without affecting the physical features of the expression. We presented angry/neutral expressions looking toward/away from the subject and depicted brain activity using fMRI. After the image acquisitions, the subject's experience of negative emotion when perceiving each stimulus was also investigated. The left amygdala showed the interaction between emotional expression and face direction, indicating higher activity for angry expressions looking toward the subjects than angry expressions looking away from them. The experienced emotion showed the corresponding interaction. Regression analysis showed a positive relation between the left amygdala activity and experienced emotion. These results suggest that the amygdala is involved in emotional but not visuoperceptual processing for emotional facial expressions, which specifically includes the decoding of emotional significance and elicitation of one's own emotions corresponding to that significance.

Neural Correlates of the Automatic Processing of Threat Facial Signals

The present study examined whether automaticity, defined here as independence from attentional modulation, is a fundamental principle of the neural systems specialized for processing social signals of environmental threat. Attention was focused on either scenes or faces presented in a single overlapping display. Facial expressions were neutral, fearful, or disgusted. Amygdala responses to facial expressions of fear, a signifier of potential physical attack, were not reduced with reduced attention to faces. In contrast, anterior insular responses to facial expressions of disgust, a signifier of potential physical contamination, were reduced with reduced attention. However, reduced attention enhanced the amygdala response to disgust expressions; this enhanced amygdala response to disgust correlated with the magnitude of attentional reduction in the anterior insular response to disgust. These results suggest that automaticity is not fundamental to the processing of all facial signals of threat, but is unique to amygdala processing of fear. Furthermore, amygdala processing of fear was not entirely automatic, coming at the expense of specificity of response. Amygdala processing is thus specific to fear only during attended processing, when cortical processing is undiminished, and more broadly tuned to threat during unattended processing, when cortical processing is diminished.

Amygdala automaticity in emotional processing.

The question addressed in this paper is whether the human amygdala processes threat-related stimuli independent of selective attention. This is considered from a functional neuroimaging perspective, describing studies in normal volunteers and patients with brain lesions. The conclusion is that the evidence for such automaticity is strong, indicating that important distinctions exist between emotion and other forms of cognition.

Differential Sensitization of Amygdala Neurons to Afferent Inputs in a Model of Arthritic Pain

Pain is associated with negative affect such as anxiety and depression. The amygdala plays a key role in emotionality and has been shown to undergo neuroplastic changes in models of affective disorders. Many neurons in the central nucleus of the amygdala (CeA) are driven by nociceptive inputs, but the role of the amygdala in persistent pain states is not known. This study is the first to address nociceptive processing by CeA neurons in a model of prolonged pain. Extracellular single-unit recordings were made from 41 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Background activity, receptive field size, and threshold were mapped, and stimulus-response functions were constructed. These parameters were measured repeatedly before and after induction of arthritis in one knee by intraarticular injections of kaolin and carrageenan. Multireceptive (MR) amygdala neurons (n = 20) with excitatory input from the knee joint responded more strongly to noxious than to innocuous mechanical stimuli of deep tissue (n = 20) and skin (n = 11). After induction of arthritis, 18 of 20 MR neurons developed enhanced responses to mechanical stimuli and expansion of receptive field size. These changes occurred with a biphasic time course (early peak: 1-1.5 h; persistent plateau phase: after 3-4 h). Responses to thermal stimuli did not change (7 of 7 neurons), but background activity (16 of 18 neurons) and electrically evoked orthodromic activity (11 of 12 neurons) increased in the arthritic state. Nociceptive-specific (NS) neurons (n = 13) showed no changes of their responses to mechanical, thermal, and electrical stimulation after induction of arthritis. A third group of neurons did not respond to somesthetic stimuli under control conditions (noSOM neurons; n = 8) but developed prolonged responses to mechanical, but not thermal, stimuli in arthritis (5 of 8 neurons). These data suggest that prolonged pain is accompanied by enhanced responsiveness of a subset of CeA neurons. Their sensitization to mechanical, but not thermal, stimuli argues against a nonspecific state of hyperexcitability. MR neurons could serve to integrate and evaluate information in the context of prolonged pain. Recruitment of noSOM neurons increases the gain of amygdala processing. NS neurons preserve the distinction between nociceptive and nonnociceptive inputs.

Affective analgesia following the administration of morphine into the amygdala of rats

The amygdala processes stimuli that threaten the individual and organizes the execution of affective behaviors that permit the individual to cope with the threat. The prototypical threat to an individual is exposure to a noxious stimulus. The present study evaluated the contribution of the amygdala in modulating the affective response of rats to noxious stimulation. Vocalization afterdischarges (VADs) are a validated model of the affective response of rats to noxious tailshock. The antinociceptive action of morphine microinjected into the amygdala on VAD thresholds was compared to its effect on the thresholds of other tailshock-elicited responses (vocalizations during shock, VDS and spinal motor reflexes, SMRs). Whereas VADs are organized within the forebrain, VDSs and SMRs are organized at medullary and spinal levels of the neuraxis, respectively. The bilateral administration of morphine into the basolateral complex of the amygdala (BLC) produced dose-dependent increases in VAD and VDS thresholds, although increases in VAD thresholds were significantly greater than increases in VDS thresholds. Administration of morphine into BLC was ineffective in elevating SMR thresholds. Morphine-induced increases in vocalization thresholds were reversed in a dose-dependent manner by microinjection of the opiate receptor antagonist methylnaloxonium into BLC. Microinjection of morphine in the vicinity to the BLC did not alter vocalization thresholds. The present results provide further evidence for the preferential involvement of the amygdala in modulation of the affective component of the pain experience.

Correlation between long latency evoked potentials from amygdala and evoked cardiac response to fear conditioned stimulus in rats

We investigated relation between activity of central nucleus of amygdala (CE) and phasic heart rate deceleration during differential fear conditioning. We found that P2 component of long-lasting event potential (EP) to CS+ but not to CS- correlated strongly with HR deceleration in the 1st second after stimulus onset. The obtained results are discussed in the light of LeDoux's and Kapp's findings showing crucial role of amygdala in processing of emotionally relevant stimulation and it's involvement in initiating autonomic responses.

Opioids and food intake: distributed functional neural pathways?

Agonists of the μ, δ, κ and ORL1opioid receptors increase food intake while opioid receptor blockade decreases food intake. The majority of the collected data related to opioids and feeding has led to the speculation that opioids are involved in meal maintenance and orosensory reward; however, some data suggest that opioids may impact feeding associated with energy needs. Based on the wide distribution of CNS opioid receptors and the presence of other neuropeptides in the vicinity of opioidergic pathways, it seems likely that opioids affect multiple feeding systems. For example, opioids in the hindbrain might be involved in both sensory and metabolic aspects of food intake, those in the amygdala in processing of ‘emotional’ properties of foods, and those in the hypothalamus in energy needs. In this review we present data which support functional diversity of opioids in feeding behavior.

Traumatic amnesia, repression, and hippocampus injury due to emotional stress, corticosteroids and enkephalins.

The role of stress, arousal, emotional trauma, and corticosteroid and enkephalin secretion on memory and the hippocampus, and the development of traumatic amnesia and repressed memory syndrome are detailed. Animal and human studies are reviewed. Trauma-induced memory deficits appear to be secondary to abnormal neocortical and hippocampal arousal, and corticosteroid and enkephalin secretion which can induce atrophy or seizures within the hippocampus, suppress hippocampal theta activity and long term potentiation, as well as injure hippocampal pyramidal cells. Predisposing factors include individual, age, and sex differences in arousal, and previous emotional trauma or temporal lobe or hippocampal injury. However, as the amygdala processes and stores emotional experiences in memory, patients may also demonstrate trauma related symptoms, including flashbacks as well as shrinking retrograde amnesia.

Sequential involvement of NMDA receptor-dependent processes in hippocampus, amygdala, entorhinal cortex and parietal cortex in memory processing.

Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus and/or in the amygdaloid nucleus, in the entorhinal cortex, and in the posterior parietal cortex, were trained in a step-down inhibitory avoidance task. At various times after training (immediately, 30, 60 or 90min) they received, through the cannulae, 0.5µl microinfusions of saline or of 5.0µg of AP5 dissolved in saline. A retention test was carried out 24h after training. Retention test performance was hindered by AP5 given into hippocampus, amygdala, or both hippocampus and amygdala immediately but not 30min post-training. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90min after training, or into the parietal cortex 60 or 90min after training, but not at earlier times. The findings suggest a sequential entry in operation, in the post-training period, of NMDA-receptor mediated mechanisms involved in memory processing; first in hippocampus and amygdala, 30min later in entorhinal cortex, and 30min later in posterior parietal cortex.

Early clinical pathologists 5: the man behind Hassall's corpuscles.

The ability to distinguish danger from safety is crucial for survival. On the other hand, anxiety disorders can result from failures to dissociate safe cues from those that predict dangerous outcomes. The amygdala plays a major role in learning and signaling danger, and recently, evidence accumulates that it also acquires information to signal safety. Traditionally, safety is explored by paradigms that change the value of a previously dangerous cue, such as extinction or reversal; or by paradigms showing that a safe cue can inhibit responses to another danger-predicting cue, as in conditioned-inhibition. In real-life scenarios, many cues are never paired or tested with danger and remain neutral all along. A detailed study of neural responses to unpaired conditioned-stimulus (CS−) can therefore indicate whether information on safety-by-comparison is also acquired in the amygdala. We designed a multiple-CS study, with CS− from both visual and auditory modalities. Using discriminative aversive-conditioning, we find that responses in the primate amygdala develop for CS− of the same modality and of a different modality from that of the aversive CS+. Moreover, we find that responses are comparable in proportion, sign (increase/decrease), onset, and magnitude. These results indicate that the primate amygdala actively acquires signals about safety, and strengthen the hypothesis that failure in amygdala processing can result in failure to distinguish dangerous cues from safe ones and lead to maladaptive behaviors.

Post-Training Memory Processing in Amygdala, Septum and Hippocampus: Role of Benzodiazepine/GABAA Receptors, and their Interaction with other Neurotransmitter Systems

Post-Training Memory Processing in Amygdala, Septum and Hippocampus: Role of Benzodiazepine/GABAA Receptors, and their Interaction with other Neurotransmitter Systems

Medial nucleus of the amygdala in the adult Syrian hamster: A quantitative Golgi analysis of gonadal hormonal regulation of neuronal morphology

The medial nucleus of the amygdala (Me) processes both chemosensory and hormonal input. In the male Syrian hamster the integrity of this nucleus is essential for normal reproductive behavior. To determine if gonadal steroids modulate neuronal structure in this nucleus, the morphology of Golgi-stained neurons in the anterior and posterior regions of Me were compared in castrated and reproductively intact adult hamsters. In castrated males, neurons in the posterior, but not the anterior, region of Me undergo structural changes, as indicated by a decrease in the mean highest dendritic branch level and mean somal area compared to intact males. To further elucidate the importance of testosterone and its metabolites in maintenance of neuronal structure in the adult, seven groups of male Syrian hamsters were studied. Animals were castrated and received a blank silastic capsule or a capsule filled with either testosterone, dihydrotestosterone, or estradiol, or two capsules containing both metabolites, dihydrotestosterone and estradiol. Two groups of reproductively intact animals were included: brains from one group were processed simultaneously with the castrated and hormone-treated groups (control intact group), and the other group was processed at the beginning of the experiment. Animals were tested for mating behavior and flank glands were measured to test whether the capsules were effective in releasing the hormones into circulation. After a 12-week survival period, the brains were processed with Golgi stain and well-impregnated neurons from the posterior Me were quantitatively analyzed for somal area, highest dendritic branch, total dendritic length, and density of spines. All the measures analyzed revealed a consistent pattern of response to the different gonadal steroids. Castration resulted in a decrease in the mean somal area, the mean highest dendritic branch, and the percentage of neurons with tertiary branch segments. Dihydrotestosterone treatment also resulted in a significant decrease in somal area, mean highest dendritic branch, and percentage of neurons with tertiary dendritic branches. In addition, the total dendritic length and spine density on terminal dendrites were reduced in these brains. The remaining hormone treatment groups were not significantly different from the control group. These results suggest that in orchidectomized male Syrian hamsters, testosterone or its aromatized form, estradiol, but not dihydrotestosterone, is sufficient to maintain the normal morphology of the neurons in the posterior part of the medial nucleus of the amygdala.

The noradrenergic system of the amygdala and aversive information processing.

Water-deprived rats were trained to drink in a passive avoidance apparatus. After reaching a predetermined latency criterion, rats were given a single 3-sec, 3-mA footshock. Immediately or 12 hr after the footshock, rats were given intracranial injections of vehicular saline, norepinephrine (NE), propranolol, or dopamine (DA) into the amygdala, internal capsule, lateral ventricles, or caudate-putamen. Subjects were tested for passive avoidance at 30 min or 24 hr following footshock. No memory deficits were seen as a consequence of short-term retention or because of proactive or toxicity effects. Retention deficits were seen in the 24 hr test only in rats injected with NE in the amygdala, internal capsule, or lateral ventricles. However, qualitative differences in stress-indicative behaviors were noted in the NE groups and in the DA-amygdala animals. The results specifically suggest that the noradrenergic system of the amygdala is involved in the long-term processing of the emotional attributes of aversive information.