Amygdala In Fear Conditioning Research Articles

Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning

The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist)-induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05µg/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor.

Thalamocortical interactions underlying visual fear conditioning in humans.

Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to "entrainment" of brain oscillations at a predefined modulation frequency. Steady-state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed-regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans.

The role of neurokinin-B-expressing neurons in the basolateral amygdala in fear conditioning and extinction

The role of neurokinin-B-expressing neurons in the basolateral amygdala in fear conditioning and extinction

Functional magnetic resonance imaging during emotion recognition in social anxiety disorder: an activation likelihood meta-analysis

Background: Social anxiety disorder (SAD) is characterized by abnormal fear and anxiety in social situations. Functional magnetic resonance imaging (fMRI) is a brain imaging technique that can be used to demonstrate neural activation to emotionally salient stimuli. However, no attempt has yet been made to statistically collate fMRI studies of brain activation, using the activation likelihood-estimate (ALE) technique, in response to emotion recognition tasks in individuals with SAD. Methods: A systematic search of fMRI studies of neural responses to socially emotive cues in SAD was undertaken. ALE meta-analysis, a voxel-based meta-analytic technique, was used to estimate the most significant activations during emotional recognition. Results: Seven studies were eligible for inclusion in the meta-analysis, constituting a total of 91 subjects with SAD, and 93 healthy controls. The most significant areas of activation during emotional vs. neutral stimuli in individuals with SAD compared to controls were: bilateral amygdala, left medial temporal lobe encompassing the entorhinal cortex, left medial aspect of the inferior temporal lobe encompassing perirhinal cortex and parahippocampus, right anterior cingulate, right globus pallidus, and distal tip of right postcentral gyrus. Conclusion: The results are consistent with neuroanatomic models of the role of the amygdala in fear conditioning, and the importance of the limbic circuitry in mediating anxiety symptoms.

3SA3-06 Roles of the prefrontal cortex and the amygdala in fear conditioning(3SA3 Multiple mechanisms of memory and synaptic plasticity underlying learning,The 47th Annual Meeting of the Biophysical Society of Japan)

3SA3-06 Roles of the prefrontal cortex and the amygdala in fear conditioning(3SA3 Multiple mechanisms of memory and synaptic plasticity underlying learning,The 47th Annual Meeting of the Biophysical Society of Japan)

Social learning of fear

Research across species highlights the critical role of the amygdala in fear conditioning. However, fear conditioning, involving direct aversive experience, is only one means by which fears can be acquired. Exploiting aversive experiences of other individuals through social fear learning is less risky. Behavioral research provides important insights into the workings of social fear learning, and the neural mechanisms are beginning to be understood. We review research suggesting that an amygdala-centered model of fear conditioning can help to explain social learning of fear through observation and instruction. We also describe how observational and instructed fear is distinguished by involvement of additional neural systems implicated in social-emotional behavior, language and explicit memory, and propose a modified conditioning model to account for social fear learning. A better understanding of social fear learning promotes integration of biological principles of learning with cultural evolution.

Animal studies of amygdala function in fear and uncertainty: Relevance to human research

This article reviews research in both animals and humans on the considerable progress made in elucidating a brain circuitry of fear, particularly the importance of the amygdala in fear conditioning. While there is considerable agreement about the participation of the amygdala in fear in both animals and humans, there are several issues about the function of the amygdala raised by the human research that have not been addressed by or may be answered by animal research. Three of these are addressed in this article: (1) is the amygdala involved in or necessary for both fear learning and unconditioned fear? (2) Does the amygdala code for intensity of fear? (3) Is the amygdala preferentially involved in fear, or is it also activated when there are no overt fear or aversive stimuli, but where the situation can be described as uncertain? We present evidence indicating that the rodent amygdala is involved in some types of fear (conditioned fear), but not all types (unconditioned fear), and may therefore have significance for a differential neurobiology of certain anxiety disorders in humans. Further, similar to the human amygdala, the rodent amygdala responds to varying intensities of aversive stimulation. Finally, it is suggested that, similar to humans, the rodent amygdala is involved in the evaluation of uncertainty. We conclude that progress on elucidating the role of the amygdala in fear is facilitated by corroboration of findings from both animal and human research.

Unconditioned stimulus pathways to the amygdala: effects of posterior thalamic and cortical lesions on fear conditioning

Plasticity in the lateral nucleus of the amygdala is thought to be critical for the acquisition of Pavlovian fear conditioning. The pathways that transmit auditory conditioned stimulus information originate in auditory processing regions of the thalamus and cortex, but the pathways mediating transmission of unconditioned stimuli to the amygdala are poorly understood. Recent studies suggest that somatosensory (footshock) unconditioned stimulus information is also relayed in parallel to the lateral nucleus of the amygdala from the thalamus (the posterior intralaminar thalamic complex, PIT) and the cortex (parietal insular cortex). In the present study we reexamined this issue. Our results showed that bilateral electrolytic lesions of the PIT alone blocked fear conditioning, whereas bilateral excitotoxic PIT lesions had no effect. These electrolytic PIT lesions did not affect fear conditioning using a loud noise as unconditioned stimulus, defining the effects of PIT lesions as a disruption of somatosensory as opposed to auditory processing. Finally, we performed combined bilateral excitotoxic lesions of the PIT nuclei and electrolytic lesions of the parietal insular cortex. These, like excitotoxic lesions of PIT alone, had no effect on the acquisition of fear conditioning. Thus, somatosensory regions of the thalamus and cortex may well be important routes of unconditioned stimulus transmission to the amygdala in fear conditioning, but information about the unconditioned somatosensory stimulus is also transmitted from other sources that send fibers through, but do not form essential synapses in, the thalamus en route to the amygdala.

Internuclear synapse in the amygdala is not facilitated in fear conditioning

The amygdala is essential for fear learning and memory. Synaptic transmission is enhanced in two pathways in the amygdala in fear conditioning. In this study we examined whether lateral (LA) to basolateral (BLA) amygdala synapses are potentiated and participate in intra-amygdala plasticity during the maintenance of fear memory. Our data showed that synaptic strength from the LA (ventrolateral) to the BLA (parvicellular) pathway was not increased after fear conditioning and suggests that this pathway does not integrate information relevant to the coding of memories in auditory fear learning.

Neuroscience of Pavlovian conditioning: a brief review.

Current knowledge on the neuronal substrates of Pavlovian conditioning in animals and man is briefly reviewed. First, work on conditioning in aplysia, that has showed amplified pre-synaptic facilitation as the basic mechanism of associative learning, is summarized. Then, two exemplars of associative learning in vertebrates, fear conditioning in rodents and eyelid conditioning in rabbits, are described and research into its neuronal substrates discussed. Research showing the role of the amygdala in fear conditioning and of the cerebellum in eyelid conditioning is reviewed, both at the circuit and cellular plasticity levels. Special attention is given to the parallelism suggested by this research between the neuronal mechanisms of conditioning and the principles of formal learning theory. Finally, recent evidence showing a similar role of the amygdala and of the cerebellum in human Pavlovian conditioning is discussed.

The emotional brain, fear, and the amygdala.

1. Considerable progress has been made over the past 20 years in relating specific circuits of the brain to emotional functions. Much of this work has involved studies of Pavlovian or classical fear conditioning, a behavioral procedure that is used to couple meaningless environmental stimuli to emotional (defense) response networks. 2. The major conclusion from studies of fear conditioning is that the amygdala plays critical role in linking external stimuli to defense responses. 3. Before describing research on the role of the amygdala in fear conditioning, though, it will be helpful to briefly examine the historical events that preceded modern research on conditioned fear.

Association of fear auras with mood and anxiety disorders after temporal lobectomy.

Epilepsy has been associated with increased occurrence of behavioral disorders. Auras reflect abnormal stimulation of brain areas in close proximity to regions from which clinical seizures originate. The purpose of our study was to investigate whether fear auras are associated with a higher rate of mood and anxiety disorders before and 1 year after temporal lobectomy. Twenty-two patients with fear auras were compared with matched groups with other auras and no auras. Neurologic and neuropsychological evaluations before, 1-2 months after, and 1 year after temporal lobectomy were reviewed for mood and anxiety disorders and psychotropic medication treatment. A logistic regression model examined effects of patient group and psychiatric status on postoperative psychiatric status. The majority of patients in the three groups experienced mood and anxiety disorders before surgery. Mood and anxiety disorders declined in the control, but not in the fear aura group after surgery. Presence of auras at 1 year after surgery was not related to psychiatric outcome. Postoperative mood and anxiety disorders were more common in patients with persistence of seizures and in those in the fear group who were seizure free. The minority of patients in all groups underwent psychotropic treatment before surgery, but the majority with fear auras underwent treatment after surgery. Postoperative mood and anxiety disorders were more common in fear aura patients after temporal lobectomy, in particular, if seizure free. Possible mechanisms include the role of the amygdala in fear conditioning, the concepts of forced normalization, and kindling.

The amygdala: vigilance and emotion.

Here we provide a review of the animal and human literature concerning the role of the amygdala in fear conditioning, considering its potential influence over autonomic and hormonal changes, motor behavior and attentional processes. A stimulus that predicts an aversive outcome will change neural transmission in the amygdala to produce the somatic, autonomic and endocrine signs of fear, as well as increased attention to that stimulus. It is now clear that the amygdala is also involved in learning about positively valenced stimuli as well as spatial and motor learning and this review strives to integrate this additional information. A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies. Where appropriate, we attempt to integrate basic information on normal amygdala function with our current understanding of psychiatric disorders, including pathological anxiety.

Neural pathways mediating Pavlovian fear conditioning using visual or auditory conditioned-stimulus in rats

It is thought that Pavlovian fear conditioning with electric shocks as unconditioned stimulus is an effective procedure to elucidate the neural substrates of learning and memory. In this paper, we start with a brief review on neural pathways of fear conditioning with an auditory or visual conditioned stimulus. Next, focusing on the amygdala that plays an critical role in these pathways, we present our experiment, in which we studied the role of subdivision of the amygdala in fear conditioning. As a result, it was obvious that two different neural pathways mediated the informations about input of the two conditioned stimulus; auditory and visual ones respectively, even if the same unconditioned stimulus; electric shock was used. Finally, we describe the future direction of the researches on this topic.

Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli

The goal of this work was to test the involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning, using auditory and visual conditioned stimuli (CSs). The acoustic startle reflex in rats was used as the behavioral index of conditioning because startle is reliably enhanced in the presence of a conditioned stimulus (CS) previously paired with a footshock. Initially, differential conditioning procedures indicated reliable discrimination between a noise CS and a visual CS. Subsequently, the effects of amygdala lesions were evaluated when both modalities were paired with shocks in the same rats. Electrolytic or ibotenic acid lesions of the central nucleus of the amygdala blocked fear-potentiated startle to both auditory and visual CSs, consistent with the idea that the central nucleus serves as a response independent, final common relay for fear conditioning. Similarly, pre- or post-training electrolytic or NMDA-induced lesions of the basolateral complex of the amygdala, which damaged the lateral nucleus, and most of the basolateral nucleus, disrupted fear-potentiated startle to both CS modalities. This finding is consistent with the suggestion that, in fear conditioning, the basolateral complex of the amygdala serves as an obligatory relay of sensory information from subcortical and cortical sensory areas to the central nucleus of the amygdala.

Involvement of subcortical and cortical afferents to the lateral nucleus of the amygdala in fear conditioning measured with fear- potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli

The goal of this work was to test the involvement, in fear conditioning, of afferents to the lateral nucleus of the amygdala originating from the auditory thalamus, auditory cortex, and perirhinal area. The acoustic startle reflex was used as the behavioral index of conditioning because it is reliably enhanced in the presence of a conditioned stimulus (CS) previously paired with a footshock. Auditory and visual CSs were used to assess the modality specificity of lesions to the above brain areas. Pre- or posttraining lesions of the entire auditory thalamus including the ventral, dorsal, and medial divisions of the medial geniculate body, the posterior intralaminar nucleus, and the suprageniculate nucleus, completely blocked fear-potentiated startle to the auditory CS, but had no effect on fear-potentiated startle to the visual CS. Posttraining lesions mostly restricted to the ventral and dorsal divisions of the medial geniculate body specifically disrupted fear-potentiated startle to the auditory CS. However, retraining in rats sustaining ventral and dorsal medial geniculate body lesions led to reliable fear-potentiated startle to the auditory CS. Posttraining lesions mostly restricted to the medial division of the medial geniculate body, posterior intralaminar, and suprageniculate nuclei did not disrupt fear-potentiated startle. These results indicate that the auditory thalamus is specifically involved, through either its direct or indirect amygdaloid afferents, in fear conditioning to auditory CSs. Pre- or posttraining lesions mostly restricted to the primary auditory cortex did not reliably attenuate fear-potentiated startle to the auditory or visual CSs. Extensive posttraining lesions of the perirhinal area (including secondary auditory cortices), but not its rostral aspect alone, blocked fear-potentiated startle to both CSs. However, reliable potentiated startle was observed to both CSs following similarly extensive pretraining lesions of the perirhinal area. Because post- but not pretraining lesions of the perirhinal area blocked fear-potentiated startle nonspecifically, at least with regard to auditory and visual CSs, the results are consistent with the involvement of the perirhinal area in general memory functions such as information storage or retrieval. Alternatively, the secondary auditory and/or perirhinal cortices might function as multimodal sensory relays to the amygdala.

The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning

Previous work has implicated projections from the acoustic thalamus to the amygdala in the classical conditioning of emotional responses to auditory stimuli. The purpose of the present studies was to determine whether the lateral amygdaloid nucleus (AL), which is a major subcortical target of projections from the acoustic thalamus, might be the sensory interface of the amygdala in emotional conditioning. Lesions were placed in AL of rats and the effects on emotional conditioning were examined. Lesions of AL, but not lesions of the striatum above or the cortex adjacent to the AL, interfered with emotional conditioning. Lesions that only partially destroyed AL or lesions placed too ventrally that completely missed AL had no effect. AL lesions did not affect the responses elicited following nonassociative (random) training. AL is thus an essential link in the circuitry through which auditory stimuli are endowed with affective properties and may function as the sensory interface of the amygdala during emotional learning.