Acquisition of Fear and Extinction in Lateral Amygdala: A Modeling Study

2010 ◽  
Author(s):  
Sandeep Pendyam ◽  
Dongbeom Kim ◽  
Gregory J. Quirk ◽  
Satish S. Nair
Keyword(s):  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Fear Learning ◽  
Cell Populations ◽  
Storage Site ◽  
Somatosensory Information ◽  
Cortical Inputs ◽  
Lateral Nucleus ◽  
And Storage

The lateral nucleus of amygdala (LA) is known to be a critical storage site for conditioned fear memory. Synaptic plasticity at auditory inputs to the dorsal LA (LAd) is critical for the formation and storage of auditory fear memories. Recent evidence suggests that two different cell populations (transient- and long-term plastic cells) are present in LAd and are responsible for fear learning. However, the mechanisms involved in the formation and storage of fear are not well understood. As an extension of previous work, a biologically realistic computational model of the LAd circuitry is developed to investigate these mechanisms. The network model consists of 52 LA pyramidal neurons and 13 interneurons. Auditory and somatosensory information reaches LA from both thalamic and cortical inputs. The model replicated the tone responses observed in the two LAd cell populations during conditioning and extinction. The model provides insights into the role of thalamic and cortical inputs in fear memory formation and storage.

scholarly journals Layer- and subregion-specific differences in the neurophysiological properties of rat medial prefrontal cortex pyramidal neurons

2018 ◽  
Vol 119 (1) ◽  
pp. 177-191 ◽  
Author(s):  
Chenghui Song ◽  
James R. Moyer
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Input Resistance ◽  
Underlying Mechanism ◽  
Fear Memory ◽  
Membrane Properties ◽  
Spike Threshold ◽  
Memory Acquisition

Medial prefrontal cortex (mPFC) is critical for the expression of long-term conditioned fear. However, the neural circuits involving fear memory acquisition and retrieval are still unclear. Two subregions within mPFC that have received a lot of attention are the prelimbic (PL) and infralimbic (IL) cortices (e.g., Santini E, Quirk GJ, Porter JT. J Neurosci 28: 4028–4036, 2008; Song C, Ehlers VL, Moyer JR Jr. J Neurosci 35: 13511–13524, 2015). Interestingly, PL and IL may play distinct roles during fear memory acquisition and retrieval but the underlying mechanism is poorly understood. One possibility is that the intrinsic membrane properties differ between these subregions. Thus, the current study was carried out to characterize the basic membrane properties of mPFC neurons in different layers and subregions. We found that pyramidal neurons in L2/3 were more hyperpolarized and less excitable than in L5. This was observed in both IL and PL and was associated with an enhanced h-current in L5 neurons. Within L2/3, IL neurons were more excitable than those in PL, which may be due to a lower spike threshold and higher input resistance in IL neurons. Within L5, the intrinsic excitability was comparable between neurons obtained in IL and PL. Thus, the heterogeneity in physiological properties of mPFC neurons may underlie the observed subregion-specific contribution of mPFC in cognitive function and emotional control, such as fear memory expression. NEW & NOTEWORTHY This is the first study to demonstrate that medial prefrontal cortical (mPFC) neurons are heterogeneous in both a layer- and a subregion-specific manner. Specifically, L5 neurons are more depolarized and more excitable than those neurons in L2/3, which is likely due to variations in h-current. Also, infralimbic neurons are more excitable than those of prelimbic neurons in layer 2/3, which may be due to differences in certain intrinsic properties, including input resistance and spike threshold.

scholarly journals Convergent coding of recent and remote fear memory in the basolateral amygdala

2021 ◽  
Author(s):  
Jianfeng Liu ◽  
Michael S. Totty ◽  
Laila Melissari ◽  
Stephen Maren
Keyword(s):  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Remote Memory ◽  
Storage Site ◽  
Long Term Storage ◽  
Behavioral Design ◽  
Within Subjects ◽  
Conditioned Freezing ◽  
Evoked Activity

Animals must learn to anticipate recently encountered threats as well as dangers experienced long ago. In both rodents and humans, the basolateral amygdala (BLA) is essential for the encoding and retrieval conditioned fear memories. Although the BLA is a putative storage site for aversive memory, recent evidence suggests that these memories undergo time-dependent reorganization and no longer require the BLA after the passage of time. To explore this question, we systematically examined the role for the BLA in recent and remote fear memory using optogenetic, electrophysiological, and calcium imaging methods in male and female Long-Evans rats. Critically, we used a behavioral design that permits within-subjects comparison of recent and remote memory at the same time point. We found that BLA c-Fos expression was similar after the retrieval of recent (1 day) or remote (2 weeks) fear memories. Extracellular recordings in awake, behaving animals revealed that the majority of BLA neurons encoded both recent and remote memories, suggesting substantial overlap in the allocation of temporally distinct events. Fiber photometric recordings of BLA principal neurons also revealed similar patterns of CS-evoked activity to recent and remote CSs. Consistent with these results, continuous or CS-specific optogenetic inhibition of BLA principal neurons impaired conditioned freezing to both recent and remote CSs. Collectively, these data reveal that single BLA neurons encode both recent and remote fear memories. This may underlie the broad generalization of fear memories across both space and time. Ultimately, these results provide robust evidence that the BLA is a long-term storage site for emotional memories.

scholarly journals Dopamine and fear memory formation in the human amygdala

2021 ◽  
Author(s):  
Andreas Frick ◽  
Johannes Björkstrand ◽  
Mark Lubberink ◽  
Allison Eriksson ◽  
Mats Fredrikson ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Dopamine Release ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Memory Formation ◽  
Fear Learning ◽  
Causative Role ◽  
Endogenous Dopamine ◽  
Positron Emission ◽  
Endogenous Dopamine Release

AbstractLearning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

scholarly journals Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model

2021 ◽  
Author(s):  
Kayla R. Nygaard ◽  
Raylynn G. Swift ◽  
Rebecca M. Glick ◽  
Rachael E. Wagner ◽  
Susan E. Maloney ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Williams Syndrome ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Receptor Activation ◽  
Oxytocin Receptor ◽  
Receptor Expression ◽  
Fear Learning ◽  
Underlying Mechanisms ◽  
Complete Deletion

ABSTRACTWilliams Syndrome is caused by a deletion of 26-28 genes on chromosome 7q11.23. Patients with this disorder have distinct behavioral phenotypes including learning deficits, anxiety, increased phobias, and hypersociability. Some studies also suggest elevated blood oxytocin and altered oxytocin receptor expression, and this oxytocin dysregulation is hypothesized to be involved in the underlying mechanisms driving a subset of these phenotypes. A ‘Complete Deletion’ mouse, modeling the hemizygous critical region deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These Complete Deletion mice also exhibited impaired fear responses in the conditioned fear task. Here, we address whether oxytocin dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an oxytocin receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in Complete Deletion mice. Thus, increased oxytocin signaling is not acutely responsible for this phenotype. We also evaluated oxytocin receptor and serotonin transporter availability in regions related to fear learning, memory, and sociability using autoradiography in wild type and Complete Deletion mice. While we identified trends in lowered oxytocin receptor expression in the lateral septal nucleus, and trends towards lowered serotonin transporter availability in the striatum and orbitofrontal cortex, we found no significant differences after correction. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.

Computational Modeling of Lateral Amygdala Neurons During Acquisition and Extinction of Conditioned Fear, Using Hebbian Learning

2006 ◽  
Author(s):  
Guoshi Li ◽  
Stacy Cheng ◽  
Frank Ko ◽  
Scott L. Raunch ◽  
Gregory Quirk ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Hebbian Learning ◽  
Conditioned Fear ◽  
Fear Learning ◽  
Central Nucleus ◽  
Projection Neurons ◽  
Basal Nucleus ◽  
Learned Fear ◽  
Main Components ◽  
Lateral Nucleus

The amygdaloid complex located within the medial temporal lobe plays an important role in the acquisition and expression of learned fear associations (Quirk et al. 2003) and contains three main components: the lateral nucleus (LA), the basal nucleus (BLA), and the central nucleus (CE) (Faber and Sah, 2002). The lateral nucleus of the amygdala (LA) is widely accepted to be a key site of plastic synaptic events that contributes to fear learning (Pare, Quirk, LeDoux, 2004). There are two main types of neurons within the LA and the BLA: principal pyramidal-like cells which form projection neurons and are glutamatergic and local circuit GABAergic interneurons (Faber and Sah, 2002). In auditory fear conditioning, convergence of tone [conditioned stimulus (CS)] and foot-shock [unconditioned stimulus (US)] inputs potentiates the synaptic transmission containing CS information from the thalamus and cortex to LA, which leads to larger responses in LA in the presentation of subsequent tones only. The increasing LA responses disinhibit the CE neurons via the intercalated (ITC) cells, eliciting fear responses via excessive projections to brain stem and hypothalamic sites (Pare, Quirk, LeDoux, 2004). As a result, rats learn to freeze to a tone that predicts a foot-shock. Once acquired, conditioned fear associations are not always expressed and repeated presentation of the tone CS in the absence of US causes conditioned fear responses to rapidly diminish, a phenomenon termed fear extinction (Quirk et al. 2003). Extinction does not erase the CS-US association, instead it forms a new memory that inhibits conditioned response (Quirk et al. 2003)

scholarly journals Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear

2010 ◽  
Vol 90 (2) ◽  
pp. 419-463 ◽  
Author(s):  
Hans-Christian Pape ◽  
Denis Pare
Keyword(s):  
Conditioned Fear ◽  
Fear Memory ◽  
Network Activity ◽  
Fear Learning ◽  
Learning Mechanisms ◽  
Memory Extinction ◽  
Basic Biology ◽  
Learned Fear ◽  
Neuronal Systems ◽  
Neuronal Functions

The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled with the fact that the underlying circuitry is evolutionarily well conserved, make it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses.

scholarly journals Dopamine facilitates fear memory formation in the human amygdala

2021 ◽  
Author(s):  
Andreas Frick ◽  
Johannes Björkstrand ◽  
Mark Lubberink ◽  
Allison Eriksson ◽  
Mats Fredrikson ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Dopamine Release ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Memory Formation ◽  
Fear Learning ◽  
Causative Role ◽  
Endogenous Dopamine ◽  
Positron Emission ◽  
Endogenous Dopamine Release

ABSTRACTLearning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced memory trace activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

A Retrieval-Extinction Paradigm to Treat Conditioned Fear Memory

2014 ◽  
Vol 22 (3) ◽  
pp. 431
Author(s):  
Xiangxing ZENG ◽  
Yanhui XIANG ◽  
Juan DU ◽  
Xifu ZHENG
Keyword(s):  
Conditioned Fear ◽  
Fear Memory

scholarly journals Observational Fear Learning in Rats: Role of Trait Anxiety and Ultrasonic Vocalization

2021 ◽  
Vol 11 (4) ◽  
pp. 423
Author(s):  
Markus Fendt ◽  
Claudia Paulina Gonzalez-Guerrero ◽  
Evelyn Kahl
Keyword(s):  
Trait Anxiety ◽  
Conditioned Fear ◽  
Ultrasonic Vocalization ◽  
Fear Learning ◽  
Anxiety State ◽  
Learning Procedure ◽  
The Social ◽  
Medium Level ◽  
Male Wistar Rats

Rats can acquire fear by observing conspecifics that express fear in the presence of conditioned fear stimuli. This process is called observational fear learning and is based on the social transmission of the demonstrator rat’s emotion and the induction of an empathy-like or anxiety state in the observer. The aim of the present study was to investigate the role of trait anxiety and ultrasonic vocalization in observational fear learning. Two experiments with male Wistar rats were performed. In the first experiment, trait anxiety was assessed in a light–dark box test before the rats were submitted to the observational fear learning procedure. In the second experiment, ultrasonic vocalization was recorded throughout the whole observational fear learning procedure, and 22 kHz and 50 kHz calls were analyzed. The results of our study show that trait anxiety differently affects direct fear learning and observational fear learning. Direct fear learning was more pronounced with higher trait anxiety, while observational fear learning was the best with a medium-level of trait anxiety. There were no indications in the present study that ultrasonic vocalization, especially emission of 22 kHz calls, but also 50 kHz calls, are critical for observational fear learning.

scholarly journals Fear conditioning and stimulus generalization in association with age in children and adolescents

2021 ◽  
Author(s):  
Julia Reinhard ◽  
Anna Slyschak ◽  
Miriam A. Schiele ◽  
Marta Andreatta ◽  
Katharina Kneer ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Fear Conditioning ◽  
Repeated Measures ◽  
Conditioned Fear ◽  
Fear Learning ◽  
Stimulus Generalization ◽  
Healthy Children ◽  
Older Individuals ◽  
Age Related ◽  
Current Task

AbstractThe aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

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