The extinction of conditioned fear: structural and molecular basis and therapeutic use

Cammarota, Martı́n; Bevilaqua, Lia R.; Vianna, Mônica Ryff Moreira Roca; Medina, Jorge H.; Izquierdo, Iván

doi:10.1590/s1516-44462006005000022

Cited by 31 publications

(7 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cued fear conditioning has been used in laboratory animals as a model of PTSD and involves pairing a neutral stimulus (tone or light as conditioned stimulus) with an aversive, unconditioned stimulus, such as a mild foot shock, thereby eliciting a freezing response to the previously neutral stimulus (89,90). During fear extinction performed 24 hours later and repeated exposure to the conditioned stimulus only, the conditioned response should be attenuated via processes of relearning (91,92).…”

Section: Oxt and Cued Fear Conditioning As A Rodent Model Of Posttraumentioning

confidence: 99%

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Neumann

Slattery

2016

Biological Psychiatry

364

276

View full text Add to dashboard Cite

The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and antistress factor of the brain, besides its many prosocial and reproductive effects. Therefore, there is substantial scientific and medical interest in its potential therapeutic use for the treatment of psychopathologies associated with anxiety, fear, and social dysfunctions, such as generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder, as well as autism and schizophrenia, among others. Focusing on preclinical studies, we review the existing evidence for the regulatory capacity of OXT to fine-tune general and social anxiety-related behaviors, as well as cued and social fear conditioning from a translational perspective. The available evidence from animal and human studies substantiates the hypothesis of an imbalance of the endogenous brain OXT system in the etiology of anxiety disorders, particularly those with a social component such as social anxiety disorder. In addition, such an imbalance of the OXT system is also likely to be the consequence of chronic OXT treatment resulting in a dose-dependent reduction in OXT receptor availability and increased anxiety.

show abstract

Section: Oxt and Cued Fear Conditioning As A Rodent Model Of Posttraumentioning

confidence: 99%

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Neumann

Slattery

2016

Biological Psychiatry

364

276

View full text Add to dashboard Cite

show abstract

“…In this context, extinction may be considered as a new form of learning, involving memory formation although preserving the original memory trace. Many studies have tried to explain neural basis underlying this stage in terms of conditioning [6,[8][9][10]; however, the neural substrates of a previously acquired spatial memory task remain elusive. The extinction of spatial learning evaluated in the Morris water maze has been studied at a behavioral level [3,4] and used in a despairand depression-like model [2,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task

Méndez-Couz

Conejo

Vallejo

et al. 2015

Behavioural Brain Research

View full text Add to dashboard Cite

“…One prominent example is extinction, a form of inhibitory learning that allows adaptive control of emotional responses like conditioned fear [14]–[16]. A deficit in fear extinction leads to maladaptive expression of fear and has been proposed to underlie mood and anxiety disorders [15], [17]–[19]. Furthermore, exposure therapy that is clinically used to treat anxiety disorders is based on an approach used to extinguish conditioned fear responses in the laboratory.…”

Section: Introductionmentioning

confidence: 99%

Directional Theta Coherence in Prefrontal Cortical to Amygdalo-Hippocampal Pathways Signals Fear Extinction

et al. 2013

View full text Add to dashboard Cite

Theta oscillations are considered crucial mechanisms in neuronal communication across brain areas, required for consolidation and retrieval of fear memories. One form of inhibitory learning allowing adaptive control of fear memory is extinction, a deficit of which leads to maladaptive fear expression potentially leading to anxiety disorders. Behavioral responses after extinction training are thought to reflect a balance of recall from extinction memory and initial fear memory traces. Therefore, we hypothesized that the initial fear memory circuits impact behavioral fear after extinction, and more specifically, that the dynamics of theta synchrony in these pathways signal the individual fear response. Simultaneous multi-channel local field and unit recordings were obtained from the infralimbic prefrontal cortex, the hippocampal CA1 and the lateral amygdala in mice. Data revealed that the pattern of theta coherence and directionality within and across regions correlated with individual behavioral responses. Upon conditioned freezing, units were phase-locked to synchronized theta oscillations in these pathways, characterizing states of fear memory retrieval. When the conditioned stimulus evoked no fear during extinction recall, theta interactions were directional with prefrontal cortical spike firing leading hippocampal and amygdalar theta oscillations. These results indicate that the directional dynamics of theta-entrained activity across these areas guide changes in appraisal of threatening stimuli during fear memory and extinction retrieval. Given that exposure therapy involves procedures and pathways similar to those during extinction of conditioned fear, one therapeutical extension might be useful that imposes artificial theta activity to prefrontal cortical-amygdalo-hippocampal pathways that mimics the directionality signaling successful extinction recall.

show abstract

The extinction of conditioned fear: structural and molecular basis and therapeutic use

Cited by 31 publications

References 53 publications

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task

Directional Theta Coherence in Prefrontal Cortical to Amygdalo-Hippocampal Pathways Signals Fear Extinction

Contact Info

Product

Resources

About