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Biological Psychiatry May 2018Associative memory formation is essential for an animal's survival by ensuring adaptive behavioral responses in an ever-changing environment. This is particularly... (Review)
Review
Associative memory formation is essential for an animal's survival by ensuring adaptive behavioral responses in an ever-changing environment. This is particularly important under conditions of immediate threats such as in fear learning. One of the key brain regions involved in associative fear learning is the amygdala. The basolateral amygdala is the main entry site for sensory information to the amygdala complex, and local plasticity in excitatory basolateral amygdala principal neurons is considered to be crucial for learning of conditioned fear responses. However, activity and plasticity of excitatory circuits are tightly controlled by local inhibitory interneurons in a spatially and temporally defined manner. In this review, we provide an updated view on how distinct interneuron subtypes in the basolateral amygdala contribute to the acquisition and extinction of conditioned fear memories.
Topics: Amygdala; Animals; Conditioning, Psychological; Fear; Humans; Nerve Net; Neural Inhibition
PubMed: 29174478
DOI: 10.1016/j.biopsych.2017.10.006 -
Psychological Bulletin Jul 2015Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory... (Review)
Review
Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning, and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. Rapid eye movement (REM) may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction, and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep's effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. (PsycINFO Database Record
Topics: Animals; Conditioning, Psychological; Extinction, Psychological; Fear; Humans; Learning; Memory; Models, Animal; Sleep
PubMed: 25894546
DOI: 10.1037/bul0000014 -
Neuroscience and Biobehavioral Reviews Oct 2021Laboratory experiments using fear conditioning and extinction protocols help lay the groundwork for designing, testing, and optimizing innovative treatments for... (Review)
Review
Laboratory experiments using fear conditioning and extinction protocols help lay the groundwork for designing, testing, and optimizing innovative treatments for anxiety-related disorders. Yet, there is limited basic research on fear conditioning and extinction in obsessive-compulsive disorder (OCD). This is surprising because exposure-based treatments based on associative learning principles are among the most popular and effective treatment options for OCD. Here, we systematically review and critically assess existing aversive conditioning and extinction studies of OCD. Across 12 studies, there was moderate evidence that OCD is associated with abnormal acquisition of conditioned responses that differ from comparison groups. There was relatively stronger evidence of OCD's association with impaired extinction processes. This included multiple studies finding elevated conditioned responses during extinction learning and poorer threat/safety discrimination during recall, although a minority of studies yielded results inconsistent with this conclusion. Overall, the conditioning model holds value for OCD research, but more work is necessary to clarify emerging patterns of results and increase clinical translational utility to the level seen in other anxiety-related disorders. We detail limitations in the literature and suggest next steps, including modeling OCD with more complex conditioning methodology (e.g., semantic/conceptual generalization, avoidance) and improving individual-differences assessment with dimensional techniques.
Topics: Conditioning, Classical; Conditioning, Psychological; Extinction, Psychological; Fear; Humans; Obsessive-Compulsive Disorder
PubMed: 34314751
DOI: 10.1016/j.neubiorev.2021.07.026 -
Learning & Memory (Cold Spring Harbor,... Oct 2022Temporal contingency is a key factor in associative learning but remains weakly investigated early in life. Few data suggest simultaneous presentation is required for...
Temporal contingency is a key factor in associative learning but remains weakly investigated early in life. Few data suggest simultaneous presentation is required for young to associate different stimuli, whereas adults can learn them sequentially. Here, we investigated the ability of newborn rabbits to perform sensory preconditioning and second-order conditioning using trace intervals between odor presentations. Strikingly, pups are able to associate odor stimuli with 10- and 30-sec intervals in sensory preconditioning and second-order conditioning, respectively. The effectiveness of higher-order trace conditioning in newborn rabbits reveals that very young animals can display complex learning despite their relative immaturity.
Topics: Animals; Animals, Newborn; Conditioning, Classical; Conditioning, Eyelid; Conditioning, Psychological; Learning; Odorants; Rabbits
PubMed: 36180128
DOI: 10.1101/lm.053607.122 -
Molecules (Basel, Switzerland) Jul 2020Taste processing is an adaptive mechanism involving complex physiological, motivational and cognitive processes. Animal models have provided relevant data about the... (Review)
Review
Taste processing is an adaptive mechanism involving complex physiological, motivational and cognitive processes. Animal models have provided relevant data about the neuroanatomical and neurobiological components of taste processing. From these models, two important domains of taste responses are described in this review. The first part focuses on the neuroanatomical and neurophysiological bases of olfactory and taste processing. The second part describes the biological and behavioral characteristics of taste learning, with an emphasis on conditioned taste aversion as a key process for the survival and health of many species, including humans.
Topics: Amygdala; Animals; Avoidance Learning; Brain Mapping; Conditioning, Psychological; Humans; Models, Neurological; Olfactory Perception; Taste Perception
PubMed: 32650432
DOI: 10.3390/molecules25143112 -
Current Topics in Behavioral... 2016Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach... (Review)
Review
Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach patients to inhibit maladaptive responses, but do not get rid of the memory itself, which explains why many patients experience a return of symptoms even after initially successful treatment. This highlights the need to discover more persistent and robust techniques to diminish maladaptive learned behaviours. One potentially promising approach is to alter the original memory, as opposed to inhibiting it, by targeting memory reconsolidation. Recent research shows that reactivating an old memory results in a period of memory flexibility and requires restorage, or reconsolidation, for the memory to persist. This reconsolidation period allows a window for modification of a specific old memory. Renewal of memory flexibility following reactivation holds great clinical potential as it enables targeting reconsolidation and changing of specific learned responses and memories that contribute to maladaptive mental states and behaviours. Here, we will review translational research on non-human animals, healthy human subjects, and clinical populations aimed at altering memories by targeting reconsolidation using biological treatments (electrical stimulation, noradrenergic antagonists) or behavioural interference (reactivation-extinction paradigm). Both approaches have been used successfully to modify aversive and appetitive memories, yet effectiveness in treating clinical populations has been limited. We will discuss that memory flexibility depends on the type of memory tested and the brain regions that underlie specific types of memory. Further, when and how we can most effectively reactivate a memory and induce flexibility is largely unclear. Finally, the development of drugs that can target reconsolidation and are safe for use in humans would optimize cross-species translations. Increasing the understanding of the mechanism and limitations of memory flexibility upon reactivation should help optimize efficacy of treatments for psychiatric patients.
Topics: Animals; Conditioning, Psychological; Electric Stimulation; Extinction, Psychological; Fear; Humans; Memory
PubMed: 27240676
DOI: 10.1007/7854_2015_5008 -
ENeuro 2022Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the...
Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signaling, which play a role in salience modulation. Consequently, hippocampal neural disinhibition may contribute to impairments in fear conditioning and salience modulation reported in schizophrenia. Therefore, we examined the effect of ventral hippocampus (VH) disinhibition in male rats on fear conditioning and salience modulation, as reflected by latent inhibition (LI), in a conditioned emotional response (CER) procedure. A flashing light was used as the conditioned stimulus (CS), and conditioned suppression was used to index conditioned fear. In experiment 1, VH disinhibition via infusion of the GABA-A receptor antagonist picrotoxin before CS pre-exposure and conditioning markedly reduced fear conditioning to both the CS and context; LI was evident in saline-infused controls but could not be detected in picrotoxin-infused rats because of the low level of fear conditioning to the CS. In experiment 2, VH picrotoxin infusions only before CS pre-exposure did not affect the acquisition of fear conditioning or LI. Together, these findings indicate that VH neural disinhibition disrupts contextual and elemental fear conditioning, without affecting the acquisition of LI. The disruption of fear conditioning resembles aversive conditioning deficits reported in schizophrenia and may reflect a disruption of neural processing both within the hippocampus and in projection sites of the hippocampus.
Topics: Animals; Conditioning, Classical; Conditioning, Psychological; Fear; Hippocampus; Male; Memory; Rats
PubMed: 34980662
DOI: 10.1523/ENEURO.0270-21.2021 -
Molecular Psychiatry Jan 2017Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety. Avoidance was... (Review)
Review
Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety. Avoidance was initially conceived of as a two-factor learning process in which fear is first acquired through Pavlovian aversive conditioning (so-called fear conditioning), and then behaviors that reduce the fear aroused by the Pavlovian conditioned stimulus are reinforced through instrumental conditioning. Over the years, criticisms of both the avoidance paradigm and the two-factor fear theory arose. By the mid-1980s, avoidance had fallen out of favor as an experimental model relevant to fear and anxiety. However, recent progress in understanding the neural basis of Pavlovian conditioning has stimulated a new wave of research on avoidance. This new work has fostered new insights into contributions of not only Pavlovian and instrumental learning but also habit learning, to avoidance, and has suggested that the reinforcing event underlying the instrumental phase should be conceived in terms of cellular and molecular events in specific circuits rather than in terms of vague notions of fear reduction. In our approach, defensive reactions (freezing), actions (avoidance) and habits (habitual avoidance) are viewed as being controlled by unique circuits that operate nonconsciously in the control of behavior, and that are distinct from the circuits that give rise to conscious feelings of fear and anxiety. These refinements, we suggest, overcome older criticisms, justifying the value of the new wave of research on avoidance, and offering a fresh perspective on the clinical implications of this work.
Topics: Animals; Anxiety; Avoidance Learning; Conditioning, Classical; Conditioning, Operant; Conditioning, Psychological; Fear; Humans; Reinforcement, Psychology
PubMed: 27752080
DOI: 10.1038/mp.2016.166 -
Trends in Neurosciences Mar 2012Conditioning and extinction of fear have traditionally been viewed as two independent learning processes for encoding representations of contexts or cues (conditioned... (Review)
Review
Conditioning and extinction of fear have traditionally been viewed as two independent learning processes for encoding representations of contexts or cues (conditioned stimuli, CS), aversive events (unconditioned stimuli, US), and their relationship. Based on the analysis of protein kinase signaling patterns in neurons of the fear circuit, we propose that fear and extinction are best conceptualized as emotional states triggered by a single CS representation with two opposing values: aversive and non-aversive. These values are conferred by the presence or absence of the US and encoded by distinct sets of kinase signaling pathways and their downstream targets. Modulating specific protein kinases thus has the potential to modify emotional states, and hence, may emerge as a promising treatment for anxiety disorders.
Topics: Animals; Conditioning, Psychological; Emotions; Extinction, Psychological; Fear; Humans; Protein Kinases; Signal Transduction
PubMed: 22118930
DOI: 10.1016/j.tins.2011.10.003 -
Behavioural Processes May 2013Learning in conditioning protocols has long been thought to depend on temporal contiguity between the conditioned stimulus and the unconditioned stimulus. This... (Review)
Review
Learning in conditioning protocols has long been thought to depend on temporal contiguity between the conditioned stimulus and the unconditioned stimulus. This conceptualization has led to a preponderance of associative models of conditioning. We suggest that trial-based associative models that posit contiguity as the primary principle underlying learning are flawed, and provide a brief review of an alternative, information theoretic approach to conditioning. The information that a CS conveys about the timing of the next US can be derived from the temporal parameters of a conditioning protocol. According to this view, a CS will support conditioned responding if, and only if, it reduces uncertainty about the timing of the next US.
Topics: Animals; Association Learning; Conditioning, Psychological; Learning; Models, Psychological; Time Factors
PubMed: 23384660
DOI: 10.1016/j.beproc.2013.01.005