Drosophila Learn Opposing Components of a Compound Food Stimulus

PubMed Central

Das, Gaurav; Klappenbach, Martín; Vrontou, Eleftheria; Perisse, Emmanuel; Clark, Christopher M.; Burke, Christopher J.; Waddell, Scott

2014-01-01

Summary Dopaminergic neurons provide value signals in mammals and insects [1–3]. During Drosophila olfactory learning, distinct subsets of dopaminergic neurons appear to assign either positive or negative value to odor representations in mushroom body neurons [4–9]. However, it is not known how flies evaluate substances that have mixed valence. Here we show that flies form short-lived aversive olfactory memories when trained with odors and sugars that are contaminated with the common insect repellent DEET. This DEET-aversive learning required the MB-MP1 dopaminergic neurons that are also required for shock learning [7]. Moreover, differential conditioning with DEET versus shock suggests that formation of these distinct aversive olfactory memories relies on a common negatively reinforcing dopaminergic mechanism. Surprisingly, as time passed after training, the behavior of DEET-sugar-trained flies reversed from conditioned odor avoidance into odor approach. In addition, flies that were compromised for reward learning exhibited a more robust and longer-lived aversive-DEET memory. These data demonstrate that flies independently process the DEET and sugar components to form parallel aversive and appetitive olfactory memories, with distinct kinetics, that compete to guide learned behavior. PMID:25042590

Effects of Propranolol, a β-noradrenergic Antagonist, on Memory Consolidation and Reconsolidation in Mice

PubMed Central

Villain, Hélène; Benkahoul, Aïcha; Drougard, Anne; Lafragette, Marie; Muzotte, Elodie; Pech, Stéphane; Bui, Eric; Brunet, Alain; Birmes, Philippe; Roullet, Pascal

2016-01-01

Memory reconsolidation impairment using the β-noradrenergic receptor blocker propranolol is a promising novel treatment avenue for patients suffering from pathogenic memories, such as post-traumatic stress disorder (PTSD). However, in order to better inform targeted treatment development, the effects of this compound on memory need to be better characterized via translational research. We examined the effects of systemic propranolol administration in mice undergoing a wide range of behavioral tests to determine more specifically which aspects of the memory consolidation and reconsolidation are impaired by propranolol. We found that propranolol (10 mg/kg) affected memory consolidation in non-aversive tasks (object recognition and object location) but not in moderately (Morris water maze (MWM) to highly (passive avoidance, conditioned taste aversion) aversive tasks. Further, propranolol impaired memory reconsolidation in the most and in the least aversive tasks, but not in the moderately aversive task, suggesting its amnesic effect was not related to task aversion. Moreover, in aquatic object recognition and location tasks in which animals were forced to behave (contrary to the classic versions of the tasks); propranolol did not impair memory reconsolidation. Taken together our results suggest that the memory impairment observed after propranolol administration may result from a modification of the emotional valence of the memory rather than a disruption of the contextual component of the memory trace. This is relevant to the use of propranolol to block memory reconsolidation in individuals with PTSD, as such a treatment would not erase the traumatic memory but only reduce the emotional valence associated with this event. PMID:27014009

Memory Elicited by Courtship Conditioning Requires Mushroom Body Neuronal Subsets Similar to Those Utilized in Appetitive Memory.

PubMed

Montague, Shelby A; Baker, Bruce S

2016-01-01

An animal's ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female. As such, courtship conditioning is not clearly categorized as either appetitive or aversive conditioning. The mushroom body (MB) region in the fruit fly brain is important for several types of memory; however, the precise subsets of intrinsic and extrinsic MB neurons necessary for courtship conditioning are unknown. Here, we disrupted synaptic signaling by driving a shibirets effector in precise subsets of MB neurons, defined by a collection of split-GAL4 drivers. Out of 75 lines tested, 32 showed defects in courtship conditioning memory. Surprisingly, we did not have any hits in the γ lobe Kenyon cells, a region previously implicated in courtship conditioning memory. We did find that several γ lobe extrinsic neurons were necessary for courtship conditioning memory. Overall, our memory hits in the dopaminergic neurons (DANs) and the mushroom body output neurons were more consistent with results from appetitive memory assays than aversive memory assays. For example, protocerebral anterior medial DANs were necessary for courtship memory, similar to appetitive memory, while protocerebral posterior lateral 1 (PPL1) DANs, important for aversive memory, were not needed. Overall, our results indicate that the MB circuits necessary for courtship conditioning memory coincide with circuits necessary for appetitive memory.

Memory Elicited by Courtship Conditioning Requires Mushroom Body Neuronal Subsets Similar to Those Utilized in Appetitive Memory

PubMed Central

Montague, Shelby A.; Baker, Bruce S.

2016-01-01

An animal’s ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female. As such, courtship conditioning is not clearly categorized as either appetitive or aversive conditioning. The mushroom body (MB) region in the fruit fly brain is important for several types of memory; however, the precise subsets of intrinsic and extrinsic MB neurons necessary for courtship conditioning are unknown. Here, we disrupted synaptic signaling by driving a shibirets effector in precise subsets of MB neurons, defined by a collection of split-GAL4 drivers. Out of 75 lines tested, 32 showed defects in courtship conditioning memory. Surprisingly, we did not have any hits in the γ lobe Kenyon cells, a region previously implicated in courtship conditioning memory. We did find that several γ lobe extrinsic neurons were necessary for courtship conditioning memory. Overall, our memory hits in the dopaminergic neurons (DANs) and the mushroom body output neurons were more consistent with results from appetitive memory assays than aversive memory assays. For example, protocerebral anterior medial DANs were necessary for courtship memory, similar to appetitive memory, while protocerebral posterior lateral 1 (PPL1) DANs, important for aversive memory, were not needed. Overall, our results indicate that the MB circuits necessary for courtship conditioning memory coincide with circuits necessary for appetitive memory. PMID:27764141

How do working-memory-related demand, reasoning ability and aversive reinforcement modulate conflict monitoring?

PubMed Central

Leue, Anja; Weber, Bernd; Beauducel, André

2014-01-01

Conflict monitoring is a process of stimulus evaluation and a pre-requisite for subsequent recruitment of cognitive control and behavioral adaptations. This study investigated how experimentally manipulated working-memory-related cognitive demand and aversive reinforcement modulate individual differences of conflict monitoring intensity and behavioral adjustments. Individual differences were assessed by means of an anxiety-related trait dimension (trait-BIS) and by means of reasoning abilities—a core determinant of intelligence. Moreover, we investigated the special role of verbal reasoning ability and figural reasoning ability for the modulation of the conflict monitoring intensity. Ninety participants performed a go/nogo task with four conditions each comprising a combination of low vs. high working-memory-related cognitive demand and low vs. high aversive reinforcement. No effect of aversive reinforcement was observed for the N2 amplitude. The fronto-central nogo N2 amplitude was more pronounced for high demand vs. low demand suggesting that cognitive demand served as an aversive costly event. Higher total reasoning abilities were associated with more intense conflict monitoring and shorter response times with increasing aversive reinforcement (defined as verbal error-feedback vs. monetary loss). Individuals with higher trait-BIS scores demonstrated a more intense conflict monitoring even in conditions with low aversive reinforcement and also a more cautious responding (i.e., response times slowing) with increasing aversive reinforcement indicating a focus on negative feedback prevention. The findings provide evidence for the conflict monitoring theory and suggest that working-memory-related demand overrules the impact of aversive reinforcement on conflict monitoring intensity. Reasoning abilities and anxiety-related traits go along with an intensification of conflict monitoring but differences in the flexibility of behavioral adjustment. PMID:24782739

The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

PubMed

Valero, E; Gómez-Milanés, I; Almela, P; Ribeiro Do Couto, B; Laorden, M L; Milanés, M V; Núñez, C

2018-06-08

Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse to drug-seeking/taking behavior triggered by opiate withdrawal-associated aversive memories. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

PubMed

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

2016-01-15

Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. Copyright © 2015 Elsevier B.V. All rights reserved.

Glucocorticoids Enhance Taste Aversion Memory via Actions in the Insular Cortex and Basolateral Amygdala

ERIC Educational Resources Information Center

Miranda, Maria Isabel; Quirarte, Gina L.; Rodriguez-Garcia, Gabriela; McGaugh, James L.; Roozendaal, Benno

2008-01-01

It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function.…

Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body.

PubMed

Perisse, Emmanuel; Owald, David; Barnstedt, Oliver; Talbot, Clifford B; Huetteroth, Wolf; Waddell, Scott

2016-06-01

In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Imagery Rescripting: The Impact of Conceptual and Perceptual Changes on Aversive Autobiographical Memories

PubMed Central

Slofstra, Christien; Nauta, Maaike H.; Holmes, Emily A.; Bockting, Claudi L. H.

2016-01-01

Background Imagery rescripting (ImRs) is a process by which aversive autobiographical memories are rendered less unpleasant or emotional. ImRs is thought only to be effective if a change in the meaning-relevant (semantic) content of the mental image is produced, according to a cognitive hypothesis of ImRs. We propose an additional hypothesis: that ImRs can also be effective by the manipulation of perceptual features of the memory, without explicitly targeting meaning-relevant content. Methods In two experiments using a within-subjects design (both N = 48, community samples), both Conceptual-ImRs—focusing on changing meaning-relevant content—and Perceptual-ImRs—focusing on changing perceptual features—were compared to Recall-only of aversive autobiographical image-based memories. An active control condition, Recall + Attentional Breathing (Recall+AB) was added in the first experiment. In the second experiment, a Positive-ImRs condition was added—changing the aversive image into a positive image that was unrelated to the aversive autobiographical memory. Effects on the aversive memory’s unpleasantness, vividness and emotionality were investigated. Results In Experiment 1, compared to Recall-only, both Conceptual-ImRs and Perceptual-ImRs led to greater decreases in unpleasantness, and Perceptual-ImRs led to greater decreases in emotionality of memories. In Experiment 2, the effects on unpleasantness were not replicated, and both Conceptual-ImRs and Perceptual-ImRs led to greater decreases in emotionality, compared to Recall-only, as did Positive-ImRs. There were no effects on vividness, and the ImRs conditions did not differ significantly from Recall+AB. Conclusions Results suggest that, in addition to traditional forms of ImRs, targeting the meaning-relevant content of an image during ImRs, relatively simple techniques focusing on perceptual aspects or positive imagery might also yield benefits. Findings require replication and extension to clinical samples. PMID:27486966

Role of dorsal hippocampus κ opioid receptors in contextual aversive memory consolidation in rats.

PubMed

Vanz, Felipe; Bicca, Maíra Assunção; Linartevichi, Vagner Fagnani; Giachero, Marcelo; Bertoglio, Leandro José; Monteiro de Lima, Thereza C

2018-06-01

The main κ opioid receptors (κORs) subtypes already described (κ 1 ORs and κ 2 ORs) are expressed in brain regions involved in aversive memory consolidation, including the dorsal hippocampus (DH). However, the role of DH κORs in consolidation of aversive memories with varied intensity and specificity is still uncertain. The present study aimed to investigate this question using pharmacological agents in rats subjected to a weak, moderate or strong contextual aversive conditioning (CAC) protocol. Antagonizing DH κORs with nor-binaltorphimine (nor-BNI), immediately after, but not 6 h later, a moderate CAC leads to intensified freezing behavior in the re-exposure to the paired context. Thus, indicating that DH κORs have an inhibitory role in the consolidation of an aversive memory. Increased DH κORs expression 1 h and 3 h after the moderate CAC was also observed. This up-regulation was absent in animals only exposed to the shock or to the context, indicating that this phenomenon requires a shock-context pairing to occur. Intra-DH nor-BNI infusion induced no changes following a weak CAC, but it was able to potentiate the expression of freezing behavior in novel and unpaired context after a strong CAC, indicating that DH κORs also modulate the consolidation of a more intense and generalized memory. Moreover, infusing the κ 2 ORs agonist GR 89696, but not the κ 1 ORs agonist U-69593, into the DH reduced the conditioned freezing expression. Nor-BNI pretreatment in a sub-effective dose prevented the κ 2 ORs agonist effects. Altogether, the present findings provide convergent evidence that κORs activation negatively modulates contextual aversive memory consolidation in rat dorsal hippocampus. Copyright © 2018. Published by Elsevier Ltd.

Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae

PubMed Central

Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S.

2016-01-01

Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes—besides other forms—a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3’5’-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution. PMID:27768692

Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae.

PubMed

Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Peters, Christina; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S

2016-10-01

Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3'5'-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.

Visual attention and emotional memory: recall of aversive pictures is partially mediated by concurrent task performance.

PubMed

Pottage, Claire L; Schaefer, Alexandre

2012-02-01

The emotional enhancement of memory is often thought to be determined by attention. However, recent evidence using divided attention paradigms suggests that attention does not play a significant role in the formation of memories for aversive pictures. We report a study that investigated this question using a paradigm in which participants had to encode lists of randomly intermixed negative and neutral pictures under conditions of full attention and divided attention followed by a free recall test. Attention was divided by a highly demanding concurrent task tapping visual processing resources. Results showed that the advantage in recall for aversive pictures was still present in the DA condition. However, mediation analyses also revealed that concurrent task performance significantly mediated the emotional enhancement of memory under divided attention. This finding suggests that visual attentional processes play a significant role in the formation of emotional memories. PsycINFO Database Record (c) 2012 APA, all rights reserved

Cholinergic dependence of taste memory formation: evidence of two distinct processes.

PubMed

Gutiérrez, Ranier; Rodriguez-Ortiz, Carlos J; De La Cruz, Vanesa; Núñez-Jaramillo, Luis; Bermudez-Rattoni, Federico

2003-11-01

Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animal's survival. A lack of recognition of a taste's consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.

Onset and Offset of Aversive Events Establish Distinct Memories Requiring Fear and Reward Networks

ERIC Educational Resources Information Center

Andreatta, Marta; Fendt, Markus; Muhlberger, Andreas; Wieser, Matthias J.; Imobersteg, Stefan; Yarali, Ayse; Gerber, Bertram; Pauli, Paul

2012-01-01

Two things are worth remembering about an aversive event: What made it happen? What made it cease? If a stimulus precedes an aversive event, it becomes a signal for threat and will later elicit behavior indicating conditioned fear. However, if the stimulus is presented upon cessation of the aversive event, it elicits behavior indicating…

Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory.

PubMed

Faria, Rodolfo Souza; Gutierres, Luís Felipe Soares; Sobrinho, Fernando César Faria; Miranda, Iris do Vale; Reis, Júlia Dos; Dias, Elayne Vieira; Sartori, Cesar Renato; Moreira, Dalmo Antonio Ribeiro

2016-08-15

Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced consolidation as well as persistence of conditioned fear memory. In addition, rats submitted to swimming exercise over six weeks showed an improved performance in the test of auditory-cued fear memory persistence, but not in the test of contextual fear memory persistence. Moreover, no significant effect from swimming exercise was observed on consolidation of both contextual and auditory fear memory. So, our study, revealing the effect of the swimming exercise on different stages of implicit memory of tone/foot shock conditioning, contributes to and complements the current knowledge about the environmental modulation of memory process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Neural Foundations of Reaction and Action in Aversive Motivation.

PubMed

Campese, Vincent D; Sears, Robert M; Moscarello, Justin M; Diaz-Mataix, Lorenzo; Cain, Christopher K; LeDoux, Joseph E

2016-01-01

Much of the early research in aversive learning concerned motivation and reinforcement in avoidance conditioning and related paradigms. When the field transitioned toward the focus on Pavlovian threat conditioning in isolation, this paved the way for the clear understanding of the psychological principles and neural and molecular mechanisms responsible for this type of learning and memory that has unfolded over recent decades. Currently, avoidance conditioning is being revisited, and with what has been learned about associative aversive learning, rapid progress is being made. We review, below, the literature on the neural substrates critical for learning in instrumental active avoidance tasks and conditioned aversive motivation.

Hippocampal Processing of Ambiguity Enhances Fear Memory

PubMed Central

Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V.; Goosens, Ki Ann

2016-01-01

Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, where dangerous situations can lead to unpleasant outcomes in unpredictable ways. Here we varied the timing of aversive events following predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of CA1 cells during aversive negative prediction errors prevented this enhancement of fear without impacting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning. PMID:28182526

Hippocampal Processing of Ambiguity Enhances Fear Memory.

PubMed

Amadi, Ugwechi; Lim, Seh Hong; Liu, Elizabeth; Baratta, Michael V; Goosens, Ki A

2017-02-01

Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events. Dorsal hippocampal inactivation also prevented ambiguity-related enhancement of fear during auditory fear conditioning under a partial-reinforcement schedule. These results reveal that information about the timing and occurrence of aversive events is rapidly acquired and that unexpectedly timed or omitted aversive events generate hippocampal signals to enhance fear learning.

The effects of eye movements on emotional memories: using an objective measure of cognitive load.

PubMed

van Veen, Suzanne C; Engelhard, Iris M; van den Hout, Marcel A

2016-01-01

Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. The working memory (WM) theory explains its efficacy: recall of an aversive memory and making eye movements (EM) both produce cognitive load, and competition for the limited WM resources reduces the memory's vividness and emotionality. The present study tested several predictions from WM theory. We hypothesized that 1) recall of an aversive autobiographical memory loads WM compared to no recall, and 2) recall with EM reduces the vividness, emotionality, and cognitive load of recalling the memory more than only recall or only cognitive effort (i.e., recall of an irrelevant memory with EM). Undergraduates (N=108) were randomly assigned to one of three conditions: 1) recall relevant memory with EM, 2) recall relevant memory without EM, and 3) recall irrelevant memory with EM. We used a random interval repetition task to measure the cognitive load of recalling the memory. Participants responded to randomly administered beeps, with or without recalling the memory. The degree to which participants slow down during recall provides an index of cognitive load. We measured the cognitive load and self-reported vividness and emotionality before, halfway through (8×24 s), and after (16×24 s) the intervention. Reaction times slowed down during memory recall compared to no recall. The recall relevant with EM condition showed a larger decrease in self-reported vividness and emotionality than the control conditions. The cognitive load of recalling the memory also decreased in this condition but not consistently more than in the control conditions. Recall of an aversive memory loads WM, but drops in vividness and emotionality do not immediately reduce the cognitive load of recalling the memory. More research is needed to find objective measures that could capture changes in the quality of the memory.

The Role of Muscarinic and Nicotinic Cholinergic Neurotransmission in Aversive Conditioning: Comparing Pavlovian Fear Conditioning and Inhibitory Avoidance

ERIC Educational Resources Information Center

Tinsley, Matthew R.; Quinn, Jennifer J.; Fanselow, Michael S.

2004-01-01

Aversive conditioning is an ideal model for studying cholinergic effects on the processes of learning and memory for several reasons. First, deficits produced by selective lesions of the anatomical structures shown to be critical for Pavlovian fear conditioning and inhibitory avoidance (such as the amygdala and hippocampus) resemble those deficits…

What are the elements of motivation for acquisition of conditioned taste aversion?

PubMed

Mita, Koichi; Okuta, Akiko; Okada, Ryuichi; Hatakeyama, Dai; Otsuka, Emi; Yamagishi, Miki; Morikawa, Mika; Naganuma, Yuki; Fujito, Yutaka; Dyakonova, Varvara; Lukowiak, Ken; Ito, Etsuro

2014-01-01

The pond snail Lymnaea stagnalis is capable of being classically conditioned to avoid food and to consolidate this aversion into a long-term memory (LTM). Previous studies have shown that the length of food deprivation is important for both the acquisition of taste aversion and its consolidation into LTM, which is referred to as conditioned taste aversion (CTA). Here we tested the hypothesis that the hemolymph glucose concentration is an important factor in the learning and memory of CTA. One-day food deprivation resulted in the best learning and memory, whereas more prolonged food deprivation had diminishing effects. Five-day food deprivation resulted in snails incapable of learning or remembering. During this food deprivation period, the hemolymph glucose concentration decreased. If snails were fed for 2days following the 5-day food deprivation, their glucose levels increased significantly and they exhibited both learning and memory, but neither learning nor memory was as good as with the 1-day food-deprived snails. Injection of the snails with insulin to reduce glucose levels resulted in better learning and memory. Insulin is also known to cause a long-term enhancement of synaptic transmission between the feeding-related neurons. On the other hand, injection of glucose into 5-day food-deprived snails did not alter their inability to learn and remember. However, if these snails were fed on sucrose for 3min, they then exhibited learning and memory formation. Our data suggest that hemolymph glucose concentration is an important factor in motivating acquisition of CTA in Lymnaea and that the action of insulin in the brain and the feeding behavior are also important factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.

PubMed

Leão, Anderson H F F; Medeiros, André M; Apolinário, Gênedy K S; Cabral, Alícia; Ribeiro, Alessandra M; Barbosa, Flávio F; Silva, Regina H

2016-05-01

The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 μg, 0.1 μg, and 0.2 μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to elucidate how these memory systems interact during aversive memory formation. Thus, the PMDAT can be useful for studying hippocampal-dependent memory when it involves emotional content. Copyright © 2016 Elsevier B.V. All rights reserved.

Discrete Serotonin Systems Mediate Memory Enhancement and Escape Latencies after Unpredicted Aversive Experience in Drosophila Place Memory

PubMed Central

Sitaraman, Divya; Kramer, Elizabeth F.; Kahsai, Lily; Ostrowski, Daniela; Zars, Troy

2017-01-01

Feedback mechanisms in operant learning are critical for animals to increase reward or reduce punishment. However, not all conditions have a behavior that can readily resolve an event. Animals must then try out different behaviors to better their situation through outcome learning. This form of learning allows for novel solutions and with positive experience can lead to unexpected behavioral routines. Learned helplessness, as a type of outcome learning, manifests in part as increases in escape latency in the face of repeated unpredicted shocks. Little is known about the mechanisms of outcome learning. When fruit fly Drosophila melanogaster are exposed to unpredicted high temperatures in a place learning paradigm, flies both increase escape latencies and have a higher memory when given control of a place/temperature contingency. Here we describe discrete serotonin neuronal circuits that mediate aversive reinforcement, escape latencies, and memory levels after place learning in the presence and absence of unexpected aversive events. The results show that two features of learned helplessness depend on the same modulatory system as aversive reinforcement. Moreover, changes in aversive reinforcement and escape latency depend on local neural circuit modulation, while memory enhancement requires larger modulation of multiple behavioral control circuits. PMID:29321732

Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory With Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

PubMed Central

Miranda, María I.; McGaugh, James L.

2004-01-01

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 μg oxotremorine and 1.25 μg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of β-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation. PMID:15169861

Memory-updating abrogates extinction of learned immunosuppression.

PubMed

Hadamitzky, Martin; Bösche, Katharina; Wirth, Timo; Buck, Benjamin; Beetz, Oliver; Christians, Uwe; Schniedewind, Björn; Lückemann, Laura; Güntürkün, Onur; Engler, Harald; Schedlowski, Manfred

2016-02-01

When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats memory-updating in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of treadmill exercise on the LiCl-induced conditioned taste aversion in rats.

PubMed

Tsuboi, Hisanori; Hirai, Yoshiyuki; Maezawa, Hitoshi; Notani, Kenji; Inoue, Nobuo; Funahashi, Makoto

2015-01-01

Studies have shown that exercise can enhance learning and memory. Conditioned taste aversion (CTA) is an avoidance behavior induced by associative memory of the taste sensation for something pleasant or neutral with a negative visceral reaction caused by the coincident action of a toxic substance that is tasteless or administered systemically. We sought to measure the effects of treadmill exercise on CTA in rats by investigating the effects of exercise on acquisition, extinction and spontaneous recovery of CTA. We made two groups of rats: an exercise group that ran on a treadmill, and a control group that did not have structured exercise periods. To condition rats to disfavor a sweet taste, consumption of a 0.1% saccharin solution in place of drinking water was paired with 0.15M LiCl (2% body weight, i.p.) to induce visceral discomfort. We measured changes of saccharin consumption during acquisition and extinction of CTA. The exercise and no-exercise groups both acquired CTA to similar levels and showed maximum extinction of CTA around 6 days after acquisition. This result indicates that exercise affects neither acquisition nor extinction of CTA. However, in testing for preservation of CTA after much longer extinction periods that included exercise or not during the intervening period, exercising animals showed a significantly lower saccharin intake, irrespective of having exercised or not during the conditioning phase of the trial. This result suggests that exercise may help to preserve aversive memory (taste aversion in this example) as evidence by the significant spontaneous recovery of aversion in exercising animals. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory with Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

ERIC Educational Resources Information Center

Miranda, Maria I.; McGaugh, James L.

2004-01-01

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the…

[Extinction and Reconsolidation of Memory].

PubMed

Zuzina, A B; Balaban, P M

2015-01-01

Retrieval of memory followed by reconsolidation can strengthen a memory, while retrieval followed by extinction results in a decrease of memory performance due to weakening of existing memory or formation of a competing memory. In our study we analyzed the behavior and responses of identified neurons involved in the network underlying aversive learning in terrestrial snail Helix, and made an attempt to describe the conditions in which the retrieval of memory leads either to extinction or reconsolidation. In the network underlying the withdrawal behavior, sensory neurons, premotor interneurons, motor neurons, and modulatory for this network serotonergic neurons are identified and recordings from representatives of these groups were made before and after aversive learning. In the network underlying feeding behavior, the premotor modulatory serotonergic interneurons and motor neurons involved in motor program of feeding are identified. Analysis of changes in neural activity after aversive learning showed that modulatory neurons of feeding behavior do not demonstrate any changes (sometimes a decrease of responses to food was observed), while responses to food in withdrawal behavior premotor interneurons changed qualitatively, from under threshold EPSPs to spike discharges. Using a specific for serotonergic neurons neurotoxin 5,7-DiHT it was shown previously that the serotonergic system is necessary for the aversive learning, but is not necessary for maintenance and retrieval of this memory. These results suggest that the serotonergic neurons that are necessary as part of a reinforcement for developing the associative changes in the network may be not necessary for the retrieval of memory. The hypothesis presented in this review concerns the activity of the "reinforcement" serotonergic neurons that is suggested to be the gate condition for the choice between extinction/reconsolidation triggered by memory retrieval: if these serotonergic neurons do not respond during the retrieval due to adaptation, habituation, changes in environment, etc., then we will observe the extinction; while if these neurons respond to the CS during memory retrieval, we will observe the reconsolidation phenomenon.

Scopolamine Impairs Appetitive But Not Aversive Trace Conditioning: Role of the Medial Prefrontal Cortex.

PubMed

Pezze, Marie-Astrid; Marshall, Hayley J; Cassaday, Helen J

2017-06-28

The muscarinic acetylcholine receptor is an important modulator of medial prefrontal cortex (mPFC) functions, such as the working memory required to bridge a trace interval in associative leaning. Aversive and appetitive trace conditioning procedures were used to examine the effects of scopolamine (0.1 and 0.5 mg/kg, i.p.) in male rats. Follow-up experiments tested the effects of microinfusion of 0.15 μg of scopolamine (0.075 μg of in 0.5 μl/side) in infralimbic (IL) versus prelimbic regions of rat mPFC, in appetitive trace and locomotor activity (LMA) procedures. Systemic scopolamine was without effect in an aversive trace conditioning procedure, but impaired appetitive conditioning at a 2 s trace interval. This effect was demonstrated as reduced responding during presentations of the conditioned stimulus (CS) and during the interstimulus interval (ISI). There was no such effect on responding during food (unconditioned stimulus, US) responding or in the intertrial interval (ITI). In contrast, systemic scopolamine dose-relatedly increased LMA. Trace conditioning was similarly impaired at the 2 s trace (shown as reduced responding to the CS and during the ISI, but not during US presentations or in the ITI) after infusion in mPFC, whereas LMA was increased (after infusion in IL only). Therefore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning and show that the observed effects cannot be attributed to reduced activity. SIGNIFICANCE STATEMENT Events are very often separated in time, in which case working memory is necessary to condition their association in "trace conditioning." The present study used conditioning variants motivated aversively with foot shock and appetitively with food. The drug scopolamine was used to block muscarinic acetylcholine receptors involved in working memory. The results show that reduced cholinergic transmission in medial prefrontal cortex (mPFC) impaired appetitive trace conditioning at a 2 s trace interval. However, scopolamine was without effect in the aversive procedure, revealing the importance of procedural differences to the demonstration of the drug effect. The finding that blockade of muscarinic receptors in mPFC impaired trace conditioning shows that these receptors are critical modulators of short-term working memory. Copyright © 2017 Pezze et al.

Scopolamine Impairs Appetitive But Not Aversive Trace Conditioning: Role of the Medial Prefrontal Cortex

PubMed Central

Pezze, Marie-Astrid; Marshall, Hayley J.

2017-01-01

The muscarinic acetylcholine receptor is an important modulator of medial prefrontal cortex (mPFC) functions, such as the working memory required to bridge a trace interval in associative leaning. Aversive and appetitive trace conditioning procedures were used to examine the effects of scopolamine (0.1 and 0.5 mg/kg, i.p.) in male rats. Follow-up experiments tested the effects of microinfusion of 0.15 μg of scopolamine (0.075 μg of in 0.5 μl/side) in infralimbic (IL) versus prelimbic regions of rat mPFC, in appetitive trace and locomotor activity (LMA) procedures. Systemic scopolamine was without effect in an aversive trace conditioning procedure, but impaired appetitive conditioning at a 2 s trace interval. This effect was demonstrated as reduced responding during presentations of the conditioned stimulus (CS) and during the interstimulus interval (ISI). There was no such effect on responding during food (unconditioned stimulus, US) responding or in the intertrial interval (ITI). In contrast, systemic scopolamine dose-relatedly increased LMA. Trace conditioning was similarly impaired at the 2 s trace (shown as reduced responding to the CS and during the ISI, but not during US presentations or in the ITI) after infusion in mPFC, whereas LMA was increased (after infusion in IL only). Therefore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning and show that the observed effects cannot be attributed to reduced activity. SIGNIFICANCE STATEMENT Events are very often separated in time, in which case working memory is necessary to condition their association in “trace conditioning.” The present study used conditioning variants motivated aversively with foot shock and appetitively with food. The drug scopolamine was used to block muscarinic acetylcholine receptors involved in working memory. The results show that reduced cholinergic transmission in medial prefrontal cortex (mPFC) impaired appetitive trace conditioning at a 2 s trace interval. However, scopolamine was without effect in the aversive procedure, revealing the importance of procedural differences to the demonstration of the drug effect. The finding that blockade of muscarinic receptors in mPFC impaired trace conditioning shows that these receptors are critical modulators of short-term working memory. PMID:28559376

Specificity of Mechanisms of Memory Reconsolidation in Snails Trained for Rejection of Two Types of Food.

PubMed

Nikitin, V P; Kozyrev, S A; Solntseva, S V

2017-01-01

Specificity of behavioral and neuronal mechanisms of impairment of long-term memory reconsolidation was studied in edible snails trained for associative skill of rejection of two types of food: raw carrots (conditioned stimulus 1) and apple (conditioned stimulus 2). In 2 days after training, the snails received protein synthesis inhibitor cycloheximide and a reminder (conditioned stimulus 1 or 2). In 3 and 14 days after cycloheximide/reminder, we observed the absence of aversive responses to the conditioned stimulus used as the reminder and preserved responses to the conditioned stimulus not used as the reminder. Moreover, we observed specific suppression of synaptic responses of command neurons of snail defensive behavior induced by the conditioned stimulus used as the reminder after cycloheximide injection and preserved synaptic responses of neurons to the other conditioned stimulus. It was hypothesized that protein synthesis-dependent synapse-specific plasticity of command neurons can be a mechanism of selective preservation of conditioned food aversion memory in snails.

Differential Involvement of Brain-Derived Neurotrophic Factor in Reconsolidation and Consolidation of Conditioned Taste Aversion Memory

PubMed Central

Wang, Yue; Zhang, Tian-Yi; Xin, Jian; Li, Ting; Yu, Hui; Li, Na; Chen, Zhe-Yu

2012-01-01

Consolidated memory can re-enter states of transient instability following reactivation, which is referred to as reconsolidation, and the exact molecular mechanisms underlying this process remain unexplored. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity and memory processes. We have recently observed that BDNF signaling in the central nuclei of the amygdala (CeA) and insular cortex (IC) was involved in the consolidation of conditioned taste aversion (CTA) memory. However, whether BDNF in the CeA or IC is required for memory reconsolidation is still unclear. In the present study, using a CTA memory paradigm, we observed increased BDNF expression in the IC but not in the CeA during CTA reconsolidation. We further determined that BDNF synthesis and signaling in the IC but not in the CeA was required for memory reconsolidation. The differential, spatial-specific roles of BDNF in memory consolidation and reconsolidation suggest that dissociative molecular mechanisms underlie reconsolidation and consolidation, which might provide novel targets for manipulating newly encoded and reactivated memories without causing universal amnesia. PMID:23185492

The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory.

PubMed

Mackiewicz, Kristen L; Sarinopoulos, Issidoros; Cleven, Krystal L; Nitschke, Jack B

2006-09-19

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.

Intra-Amygdala ZIP Injections Impair the Memory of Learned Active Avoidance Responses and Attenuate Conditioned Taste-Aversion Acquisition in Rats

ERIC Educational Resources Information Center

Gamiz, Fernando; Gallo, Milagros

2011-01-01

We have investigated the effect of protein kinase Mzeta (PKM[zeta]) inhibition in the basolateral amygdala (BLA) upon the retention of a nonspatial learned active avoidance response and conditioned taste-aversion (CTA) acquisition in rats. ZIP (10 nmol/[mu]L) injected into the BLA 24 h after training impaired retention of a learned…

Early Life Manipulations Alter Learning and Memory in Rats

PubMed Central

Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.

2012-01-01

Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985

Targeting memory processes with drugs to prevent or cure PTSD

PubMed Central

Cain, Christopher K.; Maynard, George D.; Kehne, John H.

2015-01-01

Introduction Post-traumatic stress disorder (PTSD) is a chronic debilitating psychiatric disorder resulting from exposure to a severe traumatic stressor and an area of great unmet medical need. Advances in pharmacological treatments beyond the currently approved SSRIs are needed. Areas covered Background on PTSD, as well as the neurobiology of stress responding and fear conditioning, is provided. Clinical and preclinical data for investigational agents with diverse pharmacological mechanisms are summarized. Expert opinion Advances in the understanding of stress biology and mechanisms of fear conditioning plasticity provide a rationale for treatment approaches that may reduce hyperarousal and dysfunctional aversive memories in PTSD. One challenge is to determine if these components are independent or reflect a common underlying neurobiological alteration. Numerous agents reviewed have potential for reducing PTSD core symptoms or targeted symptoms in chronic PTSD. Promising early data support drug approaches that seek to disrupt dysfunctional aversive memories by interfering with consolidation soon after trauma exposure, or in chronic PTSD, by blocking reconsolidation and/or enhancing extinction. Challenges remain for achieving selectivity when attempting to alter aversive memories. Targeting the underlying traumatic memory with a combination of pharmacological therapies applied with appropriate chronicity, and in combination with psychotherapy, is expected to substantially improve PTSD treatment. PMID:22834476

The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC.

PubMed

Wang, Weisheng; Ju, Yun-Yue; Zhou, Qi-Xin; Tang, Jian-Xin; Li, Meng; Zhang, Lei; Kang, Shuo; Chen, Zhong-Guo; Wang, Yu-Jun; Ji, Hui; Ding, Yu-Qiang; Xu, Lin; Liu, Jing-Gen

2017-07-26

Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA A receptor (GABA A R) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA A R endocytosis and CPA extinction. Knockdown of Rac1 expression within the vmPFC of rats using Rac1-shRNA suppressed GABA A R endocytosis and CPA extinction, whereas expression of a constitutively active form of Rac1 accelerated GABA A R endocytosis and CPA extinction. The crucial role of GABA A R endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABA A R endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories and reveals the sequence of molecular events that contribute to learning experience modulation of synaptic GABA A R endocytosis. SIGNIFICANCE STATEMENT This study reveals that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories associated with drug withdrawal and identifies Arc as a downstream effector of Rac1 regulations of synaptic plasticity as well as learning and memory, thereby suggesting therapeutic targets to promote extinction of the unwanted memories. Copyright © 2017 the authors 0270-6474/17/377096-15$15.00/0.

Rapid Consolidation to a radish and Protein Synthesis-Dependent Long-Term Memory after Single-Session Appetitive Olfactory Conditioning in Drosophila

PubMed Central

Krashes, Michael J.; Waddell, Scott

2008-01-01

In Drosophila, formation of aversive olfactory long-term memory (LTM) requires multiple training sessions pairing odor and electric shock punishment with rest intervals. In contrast, here we show that a single 2 min training session pairing odor with a more ethologically relevant sugar reinforcement forms long-term appetitive memory that lasts for days. Appetitive LTM has some mechanistic similarity to aversive LTM in that it can be disrupted by cycloheximide, the dCreb2-b transcriptional repressor, and the crammer and tequila LTM-specific mutations. However, appetitive LTM is completely disrupted by the radish mutation that apparently represents a distinct mechanistic phase of consolidated aversive memory. Furthermore, appetitive LTM requires activity in the dorsal paired medial neuron and mushroom body α′ β′ neuron circuit during the first hour after training and mushroom body αβ neuron output during retrieval, suggesting that appetitive middle-term memory and LTM are mechanistically linked. Last, experiments feeding and/or starving flies after training reveals a critical motivational drive that enables appetitive LTM retrieval. PMID:18354013

Rethinking a Negative Event: The Affective Impact of Ruminative versus Imagery-Based Processing of Aversive Autobiographical Memories.

PubMed

Slofstra, Christien; Eisma, Maarten C; Holmes, Emily A; Bockting, Claudi L H; Nauta, Maaike H

2017-01-01

Ruminative (abstract verbal) processing during recall of aversive autobiographical memories may serve to dampen their short-term affective impact. Experimental studies indeed demonstrate that verbal processing of non-autobiographical material and positive autobiographical memories evokes weaker affective responses than imagery-based processing. In the current study, we hypothesized that abstract verbal or concrete verbal processing of an aversive autobiographical memory would result in weaker affective responses than imagery-based processing. The affective impact of abstract verbal versus concrete verbal versus imagery-based processing during recall of an aversive autobiographical memory was investigated in a non-clinical sample ( n  = 99) using both an observational and an experimental design. Observationally, it was examined whether spontaneous use of processing modes (both state and trait measures) was associated with impact of aversive autobiographical memory recall on negative and positive affect. Experimentally, the causal relation between processing modes and affective impact was investigated by manipulating the processing mode during retrieval of the same aversive autobiographical memory. Main findings were that higher levels of trait (but not state) measures of both ruminative and imagery-based processing and depressive symptomatology were positively correlated with higher levels of negative affective impact in the observational part of the study. In the experimental part, no main effect of processing modes on affective impact of autobiographical memories was found. However, a significant moderating effect of depressive symptomatology was found. Only for individuals with low levels of depressive symptomatology, concrete verbal (but not abstract verbal) processing of the aversive autobiographical memory did result in weaker affective responses, compared to imagery-based processing. These results cast doubt on the hypothesis that ruminative processing of aversive autobiographical memories serves to avoid the negative emotions evoked by such memories. Furthermore, findings suggest that depressive symptomatology is associated with the spontaneous use and the affective impact of processing modes during recall of aversive autobiographical memories. Clinical studies are needed that examine the role of processing modes during aversive autobiographical memory recall in depression, including the potential effectiveness of targeting processing modes in therapy.

Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

PubMed

Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

2017-07-12

The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

Insular Cortex Is Involved in Consolidation of Object Recognition Memory

ERIC Educational Resources Information Center

Bermudez-Rattoni, Federico; Okuda, Shoki; Roozendaal, Benno; McGaugh, James L.

2005-01-01

Extensive evidence indicates that the insular cortex (IC), also termed gustatory cortex, is critically involved in conditioned taste aversion and taste recognition memory. Although most studies of the involvement of the IC in memory have investigated taste, there is some evidence that the IC is involved in memory that is not based on taste. In…

Aversive Olfactory Learning and Associative Long-Term Memory in "Caenorhabditis elegans"

ERIC Educational Resources Information Center

Amano, Hisayuki; Maruyama, Ichiro N.

2011-01-01

The nematode "Caenorhabditis elegans" ("C. elegans") adult hermaphrodite has 302 invariant neurons and is suited for cellular and molecular studies on complex behaviors including learning and memory. Here, we have developed protocols for classical conditioning of worms with 1-propanol, as a conditioned stimulus (CS), and hydrochloride (HCl) (pH…

Worrying affects associative fear learning: a startle fear conditioning study.

PubMed

Gazendam, Femke J; Kindt, Merel

2012-01-01

A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23) or Control condition (n = 25). After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS), whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS), skin conductance (SCR) and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS) to both the feared stimulus (CS(+)) and the originally safe stimulus (CS(-)), whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.

Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex.

PubMed

Wang, Wei-Sheng; Kang, Shuo; Liu, Wen-Tao; Li, Mu; Liu, Yao; Yu, Chuan; Chen, Jie; Chi, Zhi-Qiang; He, Ling; Liu, Jing-Gen

2012-10-03

Recent evidence suggests that histone deacetylase (HDAC) inhibitors facilitate extinction of rewarding memory of drug taking. However, little is known about the role of chromatin modification in the extinction of aversive memory of drug withdrawal. In this study, we used conditioned place aversion (CPA), a highly sensitive model for measuring aversive memory of drug withdrawal, to investigate the role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) gene expression in extinction of aversive memory. We found that CPA extinction training induced an increase in recruiting cAMP response element-binding protein (CREB) to and acetylation of histone H3 at the promoters of BDNF exon I transcript and increased BDNF mRNA and protein expression in the ventromedial prefrontal cortex (vmPFC) of acute morphine-dependent rats and that such epigenetic regulation of BDNF gene transcription could be facilitated or diminished by intra-vmPFC infusion of HDAC inhibitor trichostatin A or extracellular signal-regulated kinase (ERK) inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene) before extinction training. Correspondingly, disruption of the epigenetic regulation of BDNF gene transcription with U0126 or suppression of BDNF signaling with Trk receptor antagonist K252a or BDNF scavenger tyrosine kinase receptor B (TrkB)-Fc blocked extinction of CPA behavior. We also found that extinction training-induced activation of ERK and CREB and extinction of CPA behavior could be potentiated or suppressed by intra-vmPFC infusion of d-cycloserine, a NMDA receptor partial agonist or aminophosphonopentanoic acid, a NMDA receptor antagonist. We conclude that extinction of aversive memory of morphine withdrawal requires epigenetic regulation of BDNF gene transcription in the vmPFC through activation of the ERK-CREB signaling pathway perhaps in a NMDA receptor-dependent manner.

Implicit aversive memory under anaesthesia in animal models: a narrative review.

PubMed

Samuel, N; Taub, A H; Paz, R; Raz, A

2018-07-01

Explicit memory after anaesthesia has gained considerable attention because of its negative implications, while implicit memory, which is more elusive and lacks patients' explicit recall, has received less attention and dedicated research. This is despite the likely impact of implicit memory on postoperative long-term well-being and behaviour. Given the scarcity of human data, fear conditioning in animals offers a reliable model of implicit learning, and importantly, one where we already have a good understanding of the underlying neural circuitry in awake conditions. Animal studies provide evidence that fear conditioning occurs under anaesthesia. The effects of different anaesthetics on memory are complex, with different drugs interacting at different stages of learning. Modulatory suppressive effects can be because of context, specific drugs, and dose dependency. In some cases, low doses of general anaesthetics can actually lead to a paradoxical opposite effect. The underlying mechanisms involve several neurotransmitter systems, acting mainly in the amygdala, hippocampus, and neocortex. Here, we review animal studies of aversive conditioning under anaesthesia, discuss the complex picture that arises, identify the gaps in knowledge that require further investigation, and highlight the potential translational relevance of the models. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Sexual behavior modulates contextual fear memory through dopamine D1/D5 receptors.

PubMed

Bai, Hua-Yi; Cao, Jun; Liu, Na; Xu, Lin; Luo, Jian-Hong

2009-03-01

Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable experiences, especially instinctive behaviors such as sex, might modulate traumatic memory through a memory competition mechanism. Here, we first report that male rats persistently expressed much lower fear responses when exposed to females, but not when exposed to males, for 24 h immediately after contextual fear conditioning. Remarkably, this effect of sexual behavior was blocked by either systemic or intrahippocampal injection of the dopamine D1/D5 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) and was mimicked by systemic but not intrahippocampal injection of the D1/D5 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (SKF39393). Furthermore, as a candidate mechanism underlying contextual fear memory, the impaired induction of hippocampal long-term potentiation (LTP) elicited by conditioned fear was rescued in male rats immediately exposed to female but not male rats for 24 h. Systemic injection of the dopamine D1/D5 receptor antagonist SCH23390 or agonist SKF38393 prevented or mimicked the effect of sexual behavior on the impaired induction of hippocampal LTP. Thus, our finding suggests that dopaminergic functions may, at least partially, govern competition between contextual fear and enjoyable memories through the modulation of hippocampal LTP.

Optogenetic Induction of Aversive Taste Memory

PubMed Central

C. Keene, Alex; Masek, Pavel

2013-01-01

The Drosophila melanogaster gustatory system consists of several neuronal pathways representing diverse taste modalities. The two predominant modalities are a sweet sensing pathway that mediates attraction, and a bitter sensing pathway that mediates avoidance. A central question is how flies integrate stimuli from these pathways and generate the appropriate behavioral response. We have developed a novel assay for induction of taste memories. We demonstrate that the gustatory response to fructose is suppressed when followed by the presence of bitter quinine. We employ optogenetic neural activation using infrared laser in combination with heat sensitive channel - TRPA1 to precisely activate gustatory neurons. This optogenetic system allows for spatially and temporally controlled activation of distinct neural classes in the gustatory circuit. We directly activated bitter-sensing neurons together with presentation of fructose for remote induction of aversive taste memories. Here we report that activation of bitter-sensing neurons in the proboscis suffices as a conditioning stimulus. Spatially restricted stimulation indicates that the conditioning stimulus is indeed a signal from the bitter neurons in the proboscis and it is independent of postingestive feedback. The coincidence of temporally specific activation of bitter-sensing neurons with fructose presentation is crucial for memory formation, establishing aversive taste learning in Drosophila as associative learning. Taken together, this optogenetic system provides a powerful new tool for interrogation of the central brain circuits that mediate memory formation. PMID:22820051

Tetrahydrobiopterin improves hippocampal nitric oxide-linked long-term memory.

PubMed

Latini, Alexandra; de Bortoli da Silva, Lucila; da Luz Scheffer, Débora; Pires, Ananda Christina Staats; de Matos, Filipe José; Nesi, Renata T; Ghisoni, Karina; de Paula Martins, Roberta; de Oliveira, Paulo Alexandre; Prediger, Rui D; Ghersi, Marisa; Gabach, Laura; Pérez, Mariela Fernanda; Rubiales-Barioglio, Susana; Raisman-Vozari, Rita; Mongeau, Raymond; Lanfumey, Laurence; Aguiar, Aderbal Silva

2018-06-11

Tetrahydrobiopterin (BH4) is synthesized by the combined action of three metabolic pathways, namely de novo synthesis, recycling, and salvage pathways. The best-known function of BH4 is its mandatory action as a natural cofactor of the aromatic amino acid hydroxylases and nitric oxide synthases. Thus, BH4 is essential for the synthesis of nitric oxide, a retrograde neurotransmitter involved in learning and memory. We investigated the effect of BH4 (4-4000 pmol) intracerebroventricular administration on aversive memory, and on BH4 metabolism in the hippocampus of rodents. Memory-related behaviors were assessed in Swiss and C57BL/6 J mice, and in Wistar rats. It was consistently observed across all rodent species that BH4 facilitates aversive memory acquisition and consolidation by increasing the latency to step-down in the inhibitory avoidance task. This effect was associated with a reduced threshold to generate hippocampal long-term potentiation process. In addition, two inhibitors of memory formation (N(ω)-nitro-L-arginine methyl ester - L-Name - and dizocilpine - MK-801 -) blocked the enhanced effect of BH4 on memory, while the amnesic effect was not rescue by the co-administration of BH4 or a cGMP analog (8-Br-cGMP). The data strongly suggest that BH4 enhances aversive memory by activating the glutamatergic neurotransmission and the retrograde activity of NO. It was also demonstrated that BH2 can be converted into BH4 by activating the BH4 salvage pathway under physiological conditions in the hippocampus. This is the first evidence showing that BH4 enhances aversive memory and that the BH4 salvage pathway is active in the hippocampus. Copyright © 2018 Elsevier Inc. All rights reserved.

Steroid Hormone (20-Hydroxyecdysone) Modulates the Acquisition of Aversive Olfactory Memories in Pollen Forager Honeybees

ERIC Educational Resources Information Center

Geddes, Lisa H.; McQuillan, H. James; Aiken, Alastair; Vergoz, Vanina; Mercer, Alison R.

2013-01-01

Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, "Apis mellifera." 20-E impaired the bees' ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive…

Post-Acquisition Release of Glutamate and Norepinephrine in the Amygdala Is Involved in Taste-Aversion Memory Consolidation

ERIC Educational Resources Information Center

Guzman-Ramos, Kioko; Osorio-Gomez, Daniel; Moreno-Castilla, Perla; Bermudez-Rattoni, Federico

2012-01-01

Amygdala activity mediates the acquisition and consolidation of emotional experiences; we have recently shown that post-acquisition reactivation of this structure is necessary for the long-term storage of conditioned taste aversion (CTA). However, the specific neurotransmitters involved in such reactivation are not known. The aim of the present…

Parametric and genetic analysis of Drosophila appetitive long-term memory and sugar motivation.

PubMed

Colomb, J; Kaiser, L; Chabaud, M-A; Preat, T

2009-06-01

Distinct forms of memory can be highlighted using different training protocols. In Drosophila olfactory aversive learning, one conditioning session triggers memory formation independently of protein synthesis, while five spaced conditioning sessions lead to the formation of long-term memory (LTM), a long-lasting memory dependent on de novo protein synthesis. In contrast, one session of odour-sugar association appeared sufficient for the fly to form LTM. We designed and tuned an apparatus that facilitates repeated discriminative conditioning by alternate presentations of two odours, one being associated with sugar, as well as a new paradigm to test sugar responsiveness (SR). Our results show that both SR and short-term memory (STM) scores increase with starvation length before conditioning. The protein dependency of appetitive LTM is independent of the repetition and the spacing of training sessions, on the starvation duration and on the strength of the unconditioned stimulus. In contrast to a recent report, our test measures an abnormal SR of radish mutant flies, which might initiate their STM and LTM phenotypes. In addition, our work shows that crammer and tequila mutants, which are deficient for aversive LTM, present both an SR and an appetitive STM defect. Using the MB247-P[switch] system, we further show that tequila is required in the adult mushroom bodies for normal sugar motivation.

Context memory formation requires activity-dependent protein degradation in the hippocampus.

PubMed

Cullen, Patrick K; Ferrara, Nicole C; Pullins, Shane E; Helmstetter, Fred J

2017-11-01

Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel environment requires de novo protein synthesis in both the dorsal (dHPC) and ventral (vHPC) hippocampus. However, the role of UPS-mediated protein degradation in the consolidation of context memory in the absence of a strong aversive stimulus has not been investigated. In the present study, we used the context preexposure facilitation effect (CPFE) procedure, which allows for the dissociation of context learning from context-shock learning, to investigate the role of activity-dependent protein degradation in the dHPC and vHPC during the formation of a context memory. We report that blocking protein degradation with the proteasome inhibitor clasto-lactacystin β-lactone (βLac) or blocking protein synthesis with anisomycin (ANI) immediately after context preexposure significantly impaired context memory formation. Additionally, we examined 20S proteasome activity at different time points following context exposure and saw that the activity of proteasomes in the dHPC increases immediately after stimulus exposure while the vHPC exhibits a biphasic pattern of proteolytic activity. Taken together, these data suggest that the requirement of increased proteolysis during memory consolidation is not driven by processes triggered by the strong aversive outcome (i.e., shock) normally used to support fear conditioning. © 2017 Cullen et al.; Published by Cold Spring Harbor Laboratory Press.

A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory.

PubMed

Luft, Tatiana; Flores, Debora G; Vianna, Monica R M; Schwartsmann, Gilberto; Roesler, Rafael; Izquierdo, Ivan

2006-06-26

Although the gastrin-releasing peptide receptor has been implicated in memory consolidation, previous studies have not examined whether it is involved in extinction. Here we show that gastrin-releasing peptide receptor blockade in the hippocampus disrupts extinction of aversive memory. Male rats were trained in inhibitory avoidance conditioning and then returned repeatedly to the training context without shock on a daily basis for 3 days. Infusion of a gastrin-releasing peptide receptor antagonist or the protein synthesis inhibitor anisomycin into the dorsal hippocampus immediately after the first extinction session blocked extinction. These drugs did not affect performance in subsequent sessions when the first extinction session (1 day after training) was omitted. The results indicate that hippocampal gastrin-releasing peptide receptors are involved in memory extinction.

The Effects of Age, Priming, and Working Memory on Decision-Making.

PubMed

Wood, Meagan; Black, Sheila; Gilpin, Ansley

2016-01-11

In the current study, we examined the effects of priming and personality on risky decision-making while playing the Game of Dice Task (GDT). In the GDT, participants decide how risky they wish to be on each trial. In this particular study prior to playing the GDT, participants were randomly assigned to one of three priming conditions: Risk-Aversive, Risk-Seeking, or Control. In the Risk-Seeking condition, a fictional character benefitted from risky behavior while in the Risk-Aversive condition, a fictional character benefitted from exercising caution. Although not explicitly stated in the instructions, participants need to make "safe" rather than risky choices to optimize performance on the GDT. Participants were also given Daneman and Carpenter's assessment of working memory task. Interestingly, although older adults self-reported being more cautious than younger adults on the Domain Specific Risk Attitude scale (DOSPERT), older adults made riskier decisions than younger adults on the GDT. However, after controlling for working memory, the age differences on the GDT became insignificant, indicating that working memory mediated the relation between age and risky decisions on the GDT.

The Effects of Age, Priming, and Working Memory on Decision-Making

PubMed Central

Wood, Meagan; Black, Sheila; Gilpin, Ansley

2016-01-01

In the current study, we examined the effects of priming and personality on risky decision-making while playing the Game of Dice Task (GDT). In the GDT, participants decide how risky they wish to be on each trial. In this particular study prior to playing the GDT, participants were randomly assigned to one of three priming conditions: Risk-Aversive, Risk-Seeking, or Control. In the Risk-Seeking condition, a fictional character benefitted from risky behavior while in the Risk-Aversive condition, a fictional character benefitted from exercising caution. Although not explicitly stated in the instructions, participants need to make “safe” rather than risky choices to optimize performance on the GDT. Participants were also given Daneman and Carpenter’s assessment of working memory task. Interestingly, although older adults self-reported being more cautious than younger adults on the Domain Specific Risk Attitude scale (DOSPERT), older adults made riskier decisions than younger adults on the GDT. However, after controlling for working memory, the age differences on the GDT became insignificant, indicating that working memory mediated the relation between age and risky decisions on the GDT. PMID:26761023

NMDA and Muscarinic Receptors of the Nucleus Accumbens Have Differential Effects on Taste Memory Formation

ERIC Educational Resources Information Center

Bermudez-Rattoni, Federico; Ramirez-Lugo, Leticia; Zavala-Vega, Sergio

2006-01-01

Animals recognize a taste cue as aversive when it has been associated with post-ingestive malaise; this associative learning is known as conditioned taste aversion (CTA). When an animal consumes a new taste and no negative consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent…

Updating of aversive memories after temporal error detection is differentially modulated by mTOR across development

PubMed Central

Tallot, Lucille; Diaz-Mataix, Lorenzo; Perry, Rosemarie E.; Wood, Kira; LeDoux, Joseph E.; Mouly, Anne-Marie; Sullivan, Regina M.; Doyère, Valérie

2017-01-01

The updating of a memory is triggered whenever it is reactivated and a mismatch from what is expected (i.e., prediction error) is detected, a process that can be unraveled through the memory's sensitivity to protein synthesis inhibitors (i.e., reconsolidation). As noted in previous studies, in Pavlovian threat/aversive conditioning in adult rats, prediction error detection and its associated protein synthesis-dependent reconsolidation can be triggered by reactivating the memory with the conditioned stimulus (CS), but without the unconditioned stimulus (US), or by presenting a CS–US pairing with a different CS–US interval than during the initial learning. Whether similar mechanisms underlie memory updating in the young is not known. Using similar paradigms with rapamycin (an mTORC1 inhibitor), we show that preweaning rats (PN18–20) do form a long-term memory of the CS–US interval, and detect a 10-sec versus 30-sec temporal prediction error. However, the resulting updating/reconsolidation processes become adult-like after adolescence (PN30–40). Our results thus show that while temporal prediction error detection exists in preweaning rats, specific infant-type mechanisms are at play for associative learning and memory. PMID:28202715

Simultaneous but Not Independent Anisomycin Infusions in Insular Cortex and Amygdala Hinder Stabilization of Taste Memory when Updated

ERIC Educational Resources Information Center

Garcia-DeLaTorre, Paola; Rodriguez-Ortiz, Carlos J.; Arreguin-Martinez, Jose L.; Cruz-Castaneda, Paulina; Bermudez-Rattoni, Federico

2009-01-01

Reconsolidation has been described as a process where a consolidated memory returns to a labile state when retrieved. Growing evidence suggests that reconsolidation is, in fact, a destabilization/stabilization process that incorporates updated information to a previously consolidated memory. We used the conditioned taste aversion (CTA) task in…

The Selectivity of Aversive Memory Reconsolidation and Extinction Processes Depends on the Initial Encoding of the Pavlovian Association

ERIC Educational Resources Information Center

Debiec, Jacek; Diaz-Mataix, Lorenzo; Bush, David E. A.; Doyère, Valérie; LeDoux, Joseph E.

2013-01-01

In reconsolidation studies, memories are typically retrieved by an exposure to a single conditioned stimulus (CS). We have previously demonstrated that reconsolidation processes are CS-selective, suggesting that memories retrieved by the CS exposure are discrete and reconsolidate separately. Here, using a compound stimulus in which two distinct…

Encoding negative events under stress: high subjective arousal is related to accurate emotional memory despite misinformation exposure.

PubMed

Hoscheidt, Siobhan M; LaBar, Kevin S; Ryan, Lee; Jacobs, W Jake; Nadel, Lynn

2014-07-01

Stress at encoding affects memory processes, typically enhancing, or preserving, memory for emotional information. These effects have interesting implications for eyewitness accounts, which in real-world contexts typically involve encoding an aversive event under stressful conditions followed by potential exposure to misinformation. The present study investigated memory for a negative event encoded under stress and subsequent misinformation endorsement. Healthy young adults participated in a between-groups design with three experimental sessions conducted 48 h apart. Session one consisted of a psychosocial stress induction (or control task) followed by incidental encoding of a negative slideshow. During session two, participants were asked questions about the slideshow, during which a random subgroup was exposed to misinformation. Memory for the slideshow was tested during the third session. Assessment of memory accuracy across stress and no-stress groups revealed that stress induced just prior to encoding led to significantly better memory for the slideshow overall. The classic misinformation effect was also observed - participants exposed to misinformation were significantly more likely to endorse false information during memory testing. In the stress group, however, memory accuracy and misinformation effects were moderated by arousal experienced during encoding of the negative event. Misinformed-stress group participants who reported that the negative slideshow elicited high arousal during encoding were less likely to endorse misinformation for the most aversive phase of the story. Furthermore, these individuals showed better memory for components of the aversive slideshow phase that had been directly misinformed. Results from the current study provide evidence that stress and high subjective arousal elicited by a negative event act concomitantly during encoding to enhance emotional memory such that the most aversive aspects of the event are well remembered and subsequently more resistant to misinformation effects. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Parabrachial gustatory lesions impair taste aversion learning in rats.

PubMed

Spector, A C; Norgren, R; Grill, H J

1992-02-01

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit.

Memory Performance for Everyday Motivational and Neutral Objects Is Dissociable from Attention

PubMed Central

Schomaker, Judith; Wittmann, Bianca C.

2017-01-01

Episodic memory is typically better for items coupled with monetary reward or punishment during encoding. It is yet unclear whether memory is also enhanced for everyday objects with appetitive or aversive values learned through a lifetime of experience, and to what extent episodic memory enhancement for motivational and neutral items is attributable to attention. In a first experiment, we investigated attention to everyday motivational objects using eye-tracking during free-viewing and subsequently tested episodic memory using a remember/know procedure. Attention was directed more to aversive stimuli, as evidenced by longer viewing durations, whereas recollection was higher for both appetitive and aversive objects. In the second experiment, we manipulated the visual contrast of neutral objects through changes of contrast to further dissociate attention and memory encoding. While objects presented with high visual contrast were looked at longer, recollection was best for objects presented in unmodified, medium contrast. Generalized logistic mixed models on recollection performance showed that attention as measured by eye movements did not enhance subsequent memory, while motivational value (Experiment 1) and visual contrast (Experiment 2) had quadratic effects in opposite directions. Our findings suggest that an enhancement of incidental memory encoding for appetitive items can occur without an increase in attention and, vice versa, that enhanced attention towards salient neutral objects is not necessarily associated with memory improvement. Together, our results provide evidence for a double dissociation of attention and memory effects under certain conditions. PMID:28694774

The Orexin Component of Fasting Triggers Memory Processes Underlying Conditioned Food Selection in the Rat

ERIC Educational Resources Information Center

Ferry, Barbara; Duchamp-Viret, Patricia

2014-01-01

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor-malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion…

Interference Conditions of the Reconsolidation Process in Humans: The Role of Valence and Different Memory Systems

PubMed Central

Fernández, Rodrigo S.; Bavassi, Luz; Kaczer, Laura; Forcato, Cecilia; Pedreira, María E.

2016-01-01

Following the presentation of a reminder, consolidated memories become reactivated followed by a process of re-stabilization, which is referred to as reconsolidation. The most common behavioral tool used to reveal this process is interference produced by new learning shortly after memory reactivation. Memory interference is defined as a decrease in memory retrieval, the effect is generated when new information impairs an acquired memory. In general, the target memory and the interference task used are the same. Here we investigated how different memory systems and/or their valence could produce memory reconsolidation interference. We showed that a reactivated neutral declarative memory could be interfered by new learning of a different neutral declarative memory. Then, we revealed that an aversive implicit memory could be interfered by the presentation of a reminder followed by a threatening social event. Finally, we showed that the reconsolidation of a neutral declarative memory is unaffected by the acquisition of an aversive implicit memory and conversely, this memory remains intact when the neutral declarative memory is used as interference. These results suggest that the interference of memory reconsolidation is effective when two task rely on the same memory system or both evoke negative valence. PMID:28066212

Interference Conditions of the Reconsolidation Process in Humans: The Role of Valence and Different Memory Systems.

PubMed

Fernández, Rodrigo S; Bavassi, Luz; Kaczer, Laura; Forcato, Cecilia; Pedreira, María E

2016-01-01

Following the presentation of a reminder, consolidated memories become reactivated followed by a process of re-stabilization, which is referred to as reconsolidation. The most common behavioral tool used to reveal this process is interference produced by new learning shortly after memory reactivation. Memory interference is defined as a decrease in memory retrieval, the effect is generated when new information impairs an acquired memory. In general, the target memory and the interference task used are the same. Here we investigated how different memory systems and/or their valence could produce memory reconsolidation interference. We showed that a reactivated neutral declarative memory could be interfered by new learning of a different neutral declarative memory. Then, we revealed that an aversive implicit memory could be interfered by the presentation of a reminder followed by a threatening social event. Finally, we showed that the reconsolidation of a neutral declarative memory is unaffected by the acquisition of an aversive implicit memory and conversely, this memory remains intact when the neutral declarative memory is used as interference. These results suggest that the interference of memory reconsolidation is effective when two task rely on the same memory system or both evoke negative valence.

Choice Behavior Guided by Learned, But Not Innate, Taste Aversion Recruits the Orbitofrontal Cortex.

PubMed

Ramírez-Lugo, Leticia; Peñas-Rincón, Ana; Ángeles-Durán, Sandybel; Sotres-Bayon, Francisco

2016-10-12

The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats. Interestingly, we found that inactivation of the orbitofrontal cortex (OFC), but not the dorsal or ventral medial prefrontal cortices, blocked retrieval of choice CTA. However, OFC inactivation left retrieval of no-choice CTA intact, suggesting its role in guiding choice, but not in retrieval of CTA memory. Consistently, OFC activity increased in the choice condition compared with no-choice, as measured with c-Fos immunolabeling. Notably, OFC inactivation did not affect choice behavior when it was guided by innate taste aversion. Consistent with an anterior insular cortex (AIC) involvement in storing taste memories, we found that AIC inactivation impaired retrieval of both choice and no-choice CTA. Therefore, this study provides evidence for OFC's role in guiding choice behavior and shows that this is dissociable from AIC-dependent taste aversion memory. Together, our results suggest that OFC is required and recruited to guide choice selection between options of taste associations relayed from AIC. Survival and mental health depend on being able to choose stimuli not associated with danger. This is particularly important when danger is associated with stimuli that we ingest. Although much is known about the brain mechanisms that underlie associations with dangerous taste stimuli, very little is known about how these stored emotional associations guide behavior when it involves choice. By combining pharmacological and immunohistochemistry tools with taste-guided tasks, our study provides evidence for the key role of orbitofrontal cortex activity in choice behavior and shows that this is dissociable from the adjacent insular cortex-dependent taste aversion memory. Understanding the brain mechanisms that underlie the impact that emotional associations have on survival choice behaviors may lead to better treatments for mental disorders characterized by emotional decision-making deficits. Copyright © 2016 the authors 0270-6474/16/3610574-10$15.00/0.

Stability of retrieved memory: inverse correlation with trace dominance.

PubMed

Eisenberg, Mark; Kobilo, Tali; Berman, Diego E; Dudai, Yadin

2003-08-22

In memory consolidation, the memory trace stabilizes and becomes resistant to certain amnesic agents. The textbook account is that for any memorized item, consolidation starts and ends just once. However, evidence has accumulated that upon activation in retrieval, the trace may reconsolidate. Whereas some authors reported transient renewed susceptibility of retrieved memories to consolidation blockers, others could not detect it. Here, we report that in both conditioned taste aversion in the rat and fear conditioning in the medaka fish, the stability of retrieved memory is inversely correlated with the control of behavior by that memory. This result may explain some conflicting findings on reconsolidation of activated memories.

Overlapping memory trace indispensable for linking, but not recalling, individual memories.

PubMed

Yokose, Jun; Okubo-Suzuki, Reiko; Nomoto, Masanori; Ohkawa, Noriaki; Nishizono, Hirofumi; Suzuki, Akinobu; Matsuo, Mina; Tsujimura, Shuhei; Takahashi, Yukari; Nagase, Masashi; Watabe, Ayako M; Sasahara, Masakiyo; Kato, Fusao; Inokuchi, Kaoru

2017-01-27

Memories are not stored in isolation from other memories but are integrated into associative networks. However, the mechanisms underlying memory association remain elusive. Using two amygdala-dependent behavioral paradigms-conditioned taste aversion (CTA) and auditory-cued fear conditioning (AFC)-in mice, we found that presenting the conditioned stimulus used for the CTA task triggered the conditioned response of the AFC task after natural coreactivation of the memories. This was accompanied through an increase in the overlapping neuronal ensemble in the basolateral amygdala. Silencing of the overlapping ensemble suppressed CTA retrieval-induced freezing. However, retrieval of the original CTA or AFC memory was not affected. A small population of coshared neurons thus mediates the link between memories. They are not necessary for recalling individual memories. Copyright © 2017, American Association for the Advancement of Science.

Motivated encoding selectively promotes memory for future inconsequential semantically-related events.

PubMed

Oyarzún, Javiera P; Packard, Pau A; de Diego-Balaguer, Ruth; Fuentemilla, Lluis

2016-09-01

Neurobiological models of long-term memory explain how memory for inconsequential events fades, unless these happen before or after other relevant (i.e., rewarding or aversive) or novel events. Recently, it has been shown in humans that retrospective and prospective memories are selectively enhanced if semantically related events are paired with aversive stimuli. However, it remains unclear whether motivating stimuli, as opposed to aversive, have the same effect in humans. Here, participants performed a three phase incidental encoding task where one semantic category was rewarded during the second phase. A memory test 24h after, but not immediately after encoding, revealed that memory for inconsequential items was selectively enhanced only if items from the same category had been previously, but not subsequently, paired with rewards. This result suggests that prospective memory enhancement of reward-related information requires, like previously reported for aversive memories, of a period of memory consolidation. The current findings provide the first empirical evidence in humans that the effects of motivated encoding are selectively and prospectively prolonged over time. Copyright © 2016 Elsevier Inc. All rights reserved.

Requirement of NF-kappa B Activation in Different Mice Brain Areas during Long-Term Memory Consolidation in Two Contextual One-Trial Tasks with Opposing Valences

PubMed Central

Salles, Angeles; Krawczyk, Maria del C.; Blake, Mariano; Romano, Arturo; Boccia, Mariano M.; Freudenthal, Ramiro

2017-01-01

NF-kappa B is a transcription factor whose activation has been shown to be necessary for long-term memory consolidation in several species. NF-kappa B is activated and translocates to the nucleus of cells in a specific temporal window during consolidation. Our work focuses on a one trial learning tasks associated to the inhibitory avoidance (IA) setting. Mice were trained either receiving or not a footshock when entering a dark compartment (aversive vs. appetitive learning). Regardless of training condition (appetitive or aversive), latencies to step-through during testing were significantly different to those measured during training. Additionally, these testing latencies were also different from those of a control group that only received a shock unrelated to context. Moreover, nuclear NF-kappa B DNA-binding activity was augmented in the aversive and the appetitive tasks when compared with control and naïve animals. NF-kappa B inhibition by Sulfasalazine injected either in the Hippocampus, Amygdala or Nucleus accumbens immediately after training was able to impair retention in both training versions. Our results suggest that NF-kappa B is a critical molecular step, in different brain areas on memory consolidation. This was the case for both the IA task and also the modified version of the same task where the footshock was omitted during training. This work aims to further investigate how appetitive and aversive memories are consolidated. PMID:28439227

Plasticity in the Interoceptive System.

PubMed

Torrealba, Fernando; Madrid, Carlos; Contreras, Marco; Gómez, Karina

2017-01-01

The most outstanding manifestations of the plastic capacities of brain circuits and their neuronal and synaptic components in the adult CNS are learning and memory. A reduced number of basic plastic mechanisms underlie learning capacities at many levels and regions of the brain. The interoceptive system is no exception, and some of the most studied behavioral changes that involve learning and memory engage the interoceptive pathways at many levels of their anatomical and functional organization.In this chapter, we will review four examples of learning, mostly in rats, where the interoceptive system has a role. In the case of conditioned taste aversion, the interoceptive system is of outstanding importance. In drug addiction, the role of the insular cortex - the highest level of the interoceptive system- is unusual and complex, as many forebrain regions are engaged by the process of addiction. In the third example, neophobia, the gustatory region of the insular cortex plays a major role. Finally, the role of different areas of the insular cortex in different processes of aversive memory, particularly fear conditioning, will be reviewed.

Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus μ-opiate receptor dependent mechanisms.

PubMed

Ahmad, Tasha; Lauzon, Nicole M; de Jaeger, Xavier; Laviolette, Steven R

2013-09-25

Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a μ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.

Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats

PubMed Central

Fowler, S.W.; Ramsey, A.K.; Walker, J.M.; Serfozo, P.; Olive, M.F.; Schachtman, T.R.; Simonyi, A.

2010-01-01

Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10 mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 hours after training. However, CDPPB (at 3 mg/kg) attenuated the MK-801 (0.2 mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory. PMID:21093598

PI[subscript 3]-Kinase Cascade Has a Differential Role in Acquisition and Extinction of Conditioned Fear Memory in Juvenile and Adult Rats

ERIC Educational Resources Information Center

Slouzkey, Ilana; Maroun, Mouna

2016-01-01

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (P[subscript 3]K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear…

Memory consolidation reconfigures neural pathways involved in the suppression of emotional memories

PubMed Central

Liu, Yunzhe; Lin, Wanjun; Liu, Chao; Luo, Yuejia; Wu, Jianhui; Bayley, Peter J.; Qin, Shaozheng

2016-01-01

The ability to suppress unwanted emotional memories is crucial for human mental health. Through consolidation over time, emotional memories often become resistant to change. However, how consolidation impacts the effectiveness of emotional memory suppression is still unknown. Using event-related fMRI while concurrently recording skin conductance, we investigated the neurobiological processes underlying the suppression of aversive memories before and after overnight consolidation. Here we report that consolidated aversive memories retain their emotional reactivity and become more resistant to suppression. Suppression of consolidated memories involves higher prefrontal engagement, and less concomitant hippocampal and amygdala disengagement. In parallel, we show a shift away from hippocampal-dependent representational patterns to distributed neocortical representational patterns in the suppression of aversive memories after consolidation. These findings demonstrate rapid changes in emotional memory organization with overnight consolidation, and suggest possible neurobiological bases underlying the resistance to suppression of emotional memories in affective disorders. PMID:27898050

APIS—a novel approach for conditioning honey bees

PubMed Central

Kirkerud, Nicholas H.; Wehmann, Henja-Niniane; Galizia, C. Giovanni; Gustav, David

2013-01-01

Honey bees perform robustly in different conditioning paradigms. This makes them excellent candidates for studying mechanisms of learning and memory at both an individual and a population level. Here we introduce a novel method of honey bee conditioning: APIS, the Automatic Performance Index System. In an enclosed walking arena where the interior is covered with an electric grid, presentation of odors from either end can be combined with weak electric shocks to form aversive associations. To quantify behavioral responses, we continuously monitor the movement of the bee by an automatic tracking system. We found that escapes from one side to the other, changes in velocity as well as distance and time spent away from the punished odor are suitable parameters to describe the bee's learning capabilities. Our data show that in a short-term memory test the response rate for the conditioned stimulus (CS) in APIS correlates well with response rate obtained from conventional Proboscis Extension Response (PER)-conditioning. Additionally, we discovered that bees modulate their behavior to aversively learned odors by reducing their rate, speed and magnitude of escapes and that both generalization and extinction seem to be different between appetitive and aversive stimuli. The advantages of this automatic system make it ideal for assessing learning rates in a standardized and convenient way, and its flexibility adds to the toolbox for studying honey bee behavior. PMID:23616753

APIS-a novel approach for conditioning honey bees.

PubMed

Kirkerud, Nicholas H; Wehmann, Henja-Niniane; Galizia, C Giovanni; Gustav, David

2013-01-01

Honey bees perform robustly in different conditioning paradigms. This makes them excellent candidates for studying mechanisms of learning and memory at both an individual and a population level. Here we introduce a novel method of honey bee conditioning: APIS, the Automatic Performance Index System. In an enclosed walking arena where the interior is covered with an electric grid, presentation of odors from either end can be combined with weak electric shocks to form aversive associations. To quantify behavioral responses, we continuously monitor the movement of the bee by an automatic tracking system. We found that escapes from one side to the other, changes in velocity as well as distance and time spent away from the punished odor are suitable parameters to describe the bee's learning capabilities. Our data show that in a short-term memory test the response rate for the conditioned stimulus (CS) in APIS correlates well with response rate obtained from conventional Proboscis Extension Response (PER)-conditioning. Additionally, we discovered that bees modulate their behavior to aversively learned odors by reducing their rate, speed and magnitude of escapes and that both generalization and extinction seem to be different between appetitive and aversive stimuli. The advantages of this automatic system make it ideal for assessing learning rates in a standardized and convenient way, and its flexibility adds to the toolbox for studying honey bee behavior.

Optogenetic Activation of Presynaptic Inputs in Lateral Amygdala Forms Associative Fear Memory

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Nakajima, Ryuichi; Hyung-Su, Kim; Jeong, Yire; Augustine, George J.; Han, Jin-Hee

2014-01-01

In Pavlovian fear conditioning, the lateral amygdala (LA) has been highlighted as a key brain site for association between sensory cues and aversive stimuli. However, learning-related changes are also found in upstream sensory regions such as thalamus and cortex. To isolate the essential neural circuit components for fear memory association, we…

Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications.

PubMed

Bentz, Dorothée; Michael, Tanja; de Quervain, Dominique J-F; Wilhelm, Frank H

2010-03-01

Current neurophysiological and psychological accounts view exposure therapy as the clinical analog of extinction learning that results in persistent modifications of the fear memory involved in the pathogenesis, symptomatology, and maintenance of anxiety disorders. Evidence from studies in animals and humans indicate that glucocorticoids have the potential to facilitate the processes that underlie extinction learning during exposure therapy. Particularly, glucocorticoids can restrict retrieval of previous aversive learning episodes and enhance consolidation of memory traces relating to non-fearful responding in feared situations. Thus, glucocorticoid treatment especially in combination with exposure therapy might be a promising approach to optimize treatment of anxiety disorders. This review examines the processes involved in aversive conditioning, fear learning and fear extinction, and how glucocorticoids might enhance restructuring of fear memories during therapy. Copyright 2009 Elsevier Ltd. All rights reserved.

Distinct circuits for the formation and retrieval of an imprinted olfactory memory

PubMed Central

Jin, Xin; Pokala, Navin; Bargmann, Cornelia I.

2016-01-01

Summary Memories formed early in life are particularly stable and influential, representing privileged experiences that shape enduring behaviors. Here we show that exposing newly-hatched C. elegans to pathogenic bacteria results in persistent aversion to those bacterial odors, whereas adult exposure generates only transient aversive memory. Long-lasting imprinted aversion has a critical period in the first larval stage, and is specific to the experienced pathogen. Distinct groups of neurons are required during formation (AIB, RIM) and retrieval (AIY, RIA) of the imprinted memory. RIM synthesizes the neuromodulator tyramine, which is required in the L1 stage for learning. AIY memory retrieval neurons sense tyramine via the SER-2 receptor, which is essential for imprinted but not for adult-learned aversion. Odor responses in several neurons, most notably RIA, are altered in imprinted animals. These findings provide insight into neuronal substrates of different forms of memory, and lay a foundation for further understanding of early learning. PMID:26871629

β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways

PubMed Central

Schiff, Hillary C; Johansen, Joshua P; Hou, Mian; Bush, David E A; Smith, Emily K; Klein, JoAnna E; LeDoux, Joseph E; Sears, Robert M

2017-01-01

Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations. PMID:27762270

β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.

PubMed

Schiff, Hillary C; Johansen, Joshua P; Hou, Mian; Bush, David E A; Smith, Emily K; Klein, JoAnna E; LeDoux, Joseph E; Sears, Robert M

2017-03-01

Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.

Differential Effects of Ethanol and Midazolam upon the Devaluation of an Aversive Memory in Infant Rats

PubMed Central

Pautassi, Ricardo Marcos; Nizhnikov, Michael; Molina, Juan Carlos; Boehm, Stephen L.; Spear, Norman

2007-01-01

In infant rats, low doses of ethanol have been found to attenuate the aversive representation of an unconditioned stimulus (US) as assessed through a revaluation paradigm. This may be explained by early anxiolytic properties of EtOH. The present set of experiments was aimed at analyzing possible mechanisms of these putative anti-anxiety effects of EtOH. In a the first experiment, EtOH's effects upon the expression of citric acid-induced distress calls were compared with varying doses of midazolam (MDZ), a fast-acting GABAA agonist. Similar calming effects of 0.5 g/kg EtOH and 0.09 mg/kg MDZ were observed. Both drugs were then assessed in their capability to alter the expression of a conditioned aversion by devaluing the US. Aversive conditioning was conducted on postnatal day 14 (PD14) by pairing a lemon odor (conditioned stimulus, CS) with intraoral stimulation of citric acid (US). Control animals experienced both stimuli in an explicitly unrelated fashion. On PD 15 pups were briefly exposed to the citric acid solution under the effects of 0.5 g/kg EtOH, 0.09 mg/kg MDZ, or the respective vehicle for each drug. Pups were then tested in a two-way odor preference test (lemon vs. cineole). Both vehicle and MDZ-treated animals spent significantly less time near the lemon CS, thus expressing a citric-acid mediated odor aversion. This conditioned response was completely inhibited in pups that received 0.5 g/kg EtOH. Locomotor patterns at test were not affected by either EtOH or MDZ administration. A higher dose of MDZ (0.18 mg/kg, i.p) was also ineffective in attenuating the aversive memory. In summary, EtOH's devaluating capabilities are not shared by MDZ, indicating that these effects of EtOH may not be GABA-mediated. Appetitive motivational properties of EtOH or non-GABAA-mediated anti-anxiety effects (i.e, NMDA-related) could underlie this devaluation effect of ethanol. PMID:17936511

Cognitive function is associated with risk aversion in community-based older persons.

PubMed

Boyle, Patricia A; Yu, Lei; Buchman, Aron S; Laibson, David I; Bennett, David A

2011-09-11

Emerging data from younger and middle-aged persons suggest that cognitive ability is negatively associated with risk aversion, but this association has not been studied among older persons who are at high risk of experiencing loss of cognitive function. Using data from 369 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging, we examined the correlates of risk aversion and tested the hypothesis that cognition is negatively associated with risk aversion. Global cognition and five specific cognitive abilities were measured via detailed cognitive testing, and risk aversion was measured using standard behavioral economics questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing; potential gamble gains ranged from $21.79 to $151.19 with the gain amounts varied randomly over questions. We first examined the bivariate associations of age, education, sex, income and cognition with risk aversion. Next, we examined the associations between cognition and risk aversion via mixed models adjusted for age, sex, education, and income. Finally, we conducted sensitivity analyses to ensure that our results were not driven by persons with preclinical cognitive impairment. In bivariate analyses, sex, education, income and global cognition were associated with risk aversion. However, in a mixed effect model, only sex (estimate = -1.49, standard error (SE) = 0.39, p < 0.001) and global cognitive function (estimate = -1.05, standard error (SE) = 0.34, p < 0.003) were significantly inversely associated with risk aversion. Thus, a lower level of global cognitive function and female sex were associated with greater risk aversion. Moreover, performance on four out of the five cognitive domains was negatively related to risk aversion (i.e., semantic memory, episodic memory, working memory, and perceptual speed); performance on visuospatial abilities was not. A lower level of cognitive ability and female sex are associated with greater risk aversion in advanced age.

The hypocretin/orexin system mediates the extinction of fear memories.

PubMed

Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

2014-11-01

Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias.

The Hypocretin/Orexin System Mediates the Extinction of Fear Memories

PubMed Central

Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

2014-01-01

Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias. PMID:24930888

The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: The involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex.

PubMed

Canto-de-Souza, L; Mattioli, R

2016-04-01

Several studies using inhibitory avoidance models have demonstrated the importance of limbic structures, such as the amygdala, dorsal hippocampus and medial prefrontal cortex, in the consolidation of emotional memory. However, we aimed to investigate the role of the amygdala (AMG), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) of mice in the consolidation of step-down inhibitory avoidance and whether this avoidance would be conditioned relative to the intensity of the aversive stimulus. To test this, we bilaterally infused anisomycin (ANI-40μg/μl, a protein synthesis inhibitor) into one of these three brain areas in mice. These mice were then exposed to one of two different intensities (moderate: 0.5mA or intense: 1.5mA) in a step-down inhibitory avoidance task. We found that consolidation of both of the aversive experiences was mPFC dependent, while the AMG and DH were only required for the consolidation of the intense experience. We suggest that in moderately aversive situations, which do not represent a severe physical risk to the individual, the consolidation of aversive experiences does not depend on protein synthesis in the AMG or the DH, but only the mPFC. However, for intense aversive stimuli all three of these limbic structures are essential for the consolidation of the experience. Copyright © 2016 Elsevier Inc. All rights reserved.

p38 МАРK is Involved in Regulation of Epigenetic Mechanisms of Food Aversion Learning.

PubMed

Grinkevich, L N

2017-08-01

Consolidation of the conditioned food aversion response in Helix lucorum was associated with induction of histone H3 acetylation and methylation. We hypothesized that not only activatory, but also inhibitory p38 MARK-mediated pathways are involved in these processes. To assess the contribution of p38 MAPK to epigenetic processes, we studied the effect p38 MAPK inhibitor SB203580 on acetylation of histone H3 during training of Helix lucorum. Administration of SB203580 decreased learning-induced enhancement of histone H3 acetylation in the CNS of Helix lucorum, which was accompanied by long-term memory impairment. Thus, p38 MAPK is involved in the regulation of epigenetic mechanisms of long-term memory.

Context Memory Formation Requires Activity-Dependent Protein Degradation in the Hippocampus

ERIC Educational Resources Information Center

Cullen, Patrick K.; Ferrara, Nicole C.; Pullins, Shane E.; Helmstetter, Fred J.

2017-01-01

Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel…

Operant conditioning of autobiographical memory retrieval.

PubMed

Debeer, Elise; Raes, Filip; Williams, J Mark G; Craeynest, Miet; Hermans, Dirk

2014-01-01

Functional avoidance is considered as one of the key mechanisms underlying overgeneral autobiographical memory (OGM). According to this view OGM is regarded as a learned cognitive avoidance strategy, based on principles of operant conditioning; i.e., individuals learn to avoid the emotionally painful consequences associated with the retrieval of specific negative memories. The aim of the present study was to test one of the basic assumptions of the functional avoidance account, namely that autobiographical memory retrieval can be brought under operant control. Here 41 students were instructed to retrieve personal memories in response to 60 emotional cue words. Depending on the condition, they were punished with an aversive sound for the retrieval of specific or nonspecific memories in an operant conditioning procedure. Analyzes showed that the course of memory specificity significantly differed between conditions. After the procedure participants punished for nonspecific memories retrieved significantly more specific memories compared to participants punished for specific memories. However, whereas memory specificity significantly increased in participants punished for specific memories, it did not significantly decrease in participants punished for nonspecific memories. Thus, while our findings indicate that autobiographical memory retrieval can be brought under operant control, they do not support a functional avoidance view on OGM.

Periaqueductal gray glutamatergic, cannabinoid and vanilloid receptor interplay in defensive behavior and aversive memory formation.

PubMed

Back, Franklin P; Carobrez, Antonio P

2018-06-01

Stimulation of the midbrain periaqueductal gray matter (PAG) in humans elicits sensations of fear and impending terror, and mediates predator defensive responses in rodents. In rats, pharmacological stimulation of the dorsolateral portion of the PAG (dlPAG) with N-Methyl-d-Aspartate (NMDA) induces aversive conditioning that acts as an unconditioned stimulus (US). In the present work, we investigated the interplay between the vanilloid TRPV1 and cannabinoid CB1 receptors in the NMDA-dlPAG defensive response and in subsequent aversive learning. Rats were subjected to dlPAG NMDA infusion in an olfactory conditioned stimulus (CS) task allowing the evaluation of immediate and long-term defensive behavioral responses during CS presentation. The results indicated that an intermediate dose of NMDA (50 pmol) induced both immediate and long-term effects. A sub-effective dose of NMDA (25 pmol) was potentiated by the TRPV1 receptor agonist capsaicin (CAP, 1 nmol) and the CB1 receptor antagonist, AM251 (200 pmol). CAP (10 nmol) or the combination of CAP (1 nmol) and AM251 (200 pmol) induced long-term effects without increasing immediate defensive responses. The glutamate release inhibitor riluzole (2 or 4 nmol) and the AMPA/kainate receptor antagonist DNQX (2 or 4 nmol) potentiated the immediate effects but blocked the long-term effects. The results showed that immediate defensive responses rely on NMDA receptors, and aversive learning on the fine-tuning of TRPV1, CB1, metabotropic glutamate and AMPA receptors located in pre- and postsynaptic membranes. In conclusion, the activity of the dlPAG determines core affective aspects of aversive memory formation controlled by local TRPV1/CB1 balance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Psychophysiology of prospective memory.

PubMed

Rothen, Nicolas; Meier, Beat

2014-01-01

Prospective memory involves the self-initiated retrieval of an intention upon an appropriate retrieval cue. Cue identification can be considered as an orienting reaction and may thus trigger a psychophysiological response. Here we present two experiments in which skin conductance responses (SCRs) elicited by prospective memory cues were compared to SCRs elicited by aversive stimuli to test whether a single prospective memory cue triggers a similar SCR as an aversive stimulus. In Experiment 2 we also assessed whether cue specificity had a differential influence on prospective memory performance and on SCRs. We found that detecting a single prospective memory cue is as likely to elicit a SCR as an aversive stimulus. Missed prospective memory cues also elicited SCRs. On a behavioural level, specific intentions led to better prospective memory performance. However, on a psychophysiological level specificity had no influence. More generally, the results indicate reliable SCRs for prospective memory cues and point to psychophysiological measures as valuable approach, which offers a new way to study one-off prospective memory tasks. Moreover, the findings are consistent with a theory that posits multiple prospective memory retrieval stages.

Cognitive function is associated with risk aversion in community-based older persons

PubMed Central

2011-01-01

Background Emerging data from younger and middle-aged persons suggest that cognitive ability is negatively associated with risk aversion, but this association has not been studied among older persons who are at high risk of experiencing loss of cognitive function. Methods Using data from 369 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging, we examined the correlates of risk aversion and tested the hypothesis that cognition is negatively associated with risk aversion. Global cognition and five specific cognitive abilities were measured via detailed cognitive testing, and risk aversion was measured using standard behavioral economics questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing; potential gamble gains ranged from $21.79 to $151.19 with the gain amounts varied randomly over questions. We first examined the bivariate associations of age, education, sex, income and cognition with risk aversion. Next, we examined the associations between cognition and risk aversion via mixed models adjusted for age, sex, education, and income. Finally, we conducted sensitivity analyses to ensure that our results were not driven by persons with preclinical cognitive impairment. Results In bivariate analyses, sex, education, income and global cognition were associated with risk aversion. However, in a mixed effect model, only sex (estimate = -1.49, standard error (SE) = 0.39, p < 0.001) and global cognitive function (estimate = -1.05, standard error (SE) = 0.34, p < 0.003) were significantly inversely associated with risk aversion. Thus, a lower level of global cognitive function and female sex were associated with greater risk aversion. Moreover, performance on four out of the five cognitive domains was negatively related to risk aversion (i.e., semantic memory, episodic memory, working memory, and perceptual speed); performance on visuospatial abilities was not. Conclusion A lower level of cognitive ability and female sex are associated with greater risk aversion in advanced age. PMID:21906402

Medial Amygdala Lesions Selectively Block Aversive Pavlovian–Instrumental Transfer in Rats

PubMed Central

McCue, Margaret G.; LeDoux, Joseph E.; Cain, Christopher K.

2014-01-01

Pavlovian conditioned stimuli (CSs) play an important role in the reinforcement and motivation of instrumental active avoidance (AA). Conditioned threats can also invigorate ongoing AA responding [aversive Pavlovian–instrumental transfer (PIT)]. The neural circuits mediating AA are poorly understood, although lesion studies suggest that lateral, basal, and central amygdala nuclei, as well as infralimbic prefrontal cortex, make key, and sometimes opposing, contributions. We recently completed an extensive analysis of brain c-Fos expression in good vs. poor avoiders following an AA test (Martinez et al., 2013, Learning and Memory). This analysis identified medial amygdala (MeA) as a potentially important region for Pavlovian motivation of instrumental actions. MeA is known to mediate defensive responding to innate threats as well as social behaviors, but its role in mediating aversive Pavlovian–instrumental interactions is unknown. We evaluated the effect of MeA lesions on Pavlovian conditioning, Sidman two-way AA conditioning (shuttling) and aversive PIT in rats. Mild footshocks served as the unconditioned stimulus in all conditioning phases. MeA lesions had no effect on AA but blocked the expression of aversive PIT and 22 kHz ultrasonic vocalizations in the AA context. Interestingly, MeA lesions failed to affect Pavlovian freezing to discrete threats but reduced freezing to contextual threats when assessed outside of the AA chamber. These findings differentiate MeA from lateral and central amygdala, as lesions of these nuclei disrupt Pavlovian freezing and aversive PIT, but have opposite effects on AA performance. Taken together, these results suggest that MeA plays a selective role in the motivation of instrumental avoidance by general or uncertain Pavlovian threats. PMID:25278858

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long-term maintenance during consolidation.

PubMed

Troyner, Fernanda; Bicca, Maira A; Bertoglio, Leandro J

2018-05-10

The thalamic nucleus reuniens (NR) has been shown to support bidirectional medial prefrontal cortex-hippocampus communication and synchronization relevant for cognitive processing. Using non-selective or prolonged inactivation of the NR, previous studies reported its activity positively modulates aversive memory consolidation. Here we examined the NR's role in consolidating contextual fear memories with varied strength, at both recent and more remote time points, using muscimol-induced temporary inactivation in rats. Results indicate the NR negatively modulates fear memory intensity, specificity and long-term maintenance. The more intense, generalized and enduring fear memory induced by NR inactivation during consolidation was also less prone to behavioral suppression by extinction or reconsolidation disruption induced by clonidine, an alpha-2 adrenergic receptor agonist. Lastly, we used immunohistochemistry for Arc protein, which is involved in synaptic modifications underlying aversive memory consolidation, to investigate whether treatment condition and/or conditioning status could change its levels in the NR, the hippocampus (dorsal and ventral CA1 subregions) and the medial prefrontal cortex (anterior cingulate, prelimbic and infralimbic subregions). Results indicate a significant imbalance in the number of Arc-expressing neurons in the brain areas investigated in muscimol fear conditioned animals when compared with controls. Collectively, present results provide convergent evidence for the NR's role as a hub regulating quantitative and qualitative aspects of a contextual fear memory during its consolidation that seem to influence the subsequent susceptibility to experimental interventions aiming at attenuating its expression. They also indicate the selectivity and duration of a given inactivation approach may influence its outcomes. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Acquisition and retrieval of conditioned taste aversion is impaired by brain damage caused by two hours of pilocarpine-induced status epilepticus.

PubMed

Sroubek, J; Hort, J; Komárek, V; Langmeier, M; Brozek, G

2001-01-01

The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.

Where There is Smoke There is Fear-Impaired Contextual Inhibition of Conditioned Fear in Smokers.

PubMed

Haaker, Jan; Lonsdorf, Tina B; Schümann, Dirk; Bunzeck, Nico; Peters, Jan; Sommer, Tobias; Kalisch, Raffael

2017-07-01

The odds-ratio of smoking is elevated in populations with neuropsychiatric diseases, in particular in the highly prevalent diagnoses of post-traumatic stress and anxiety disorders. Yet, the association between smoking and a key dimensional phenotype of these disorders-maladaptive deficits in fear learning and fear inhibition-is unclear. We therefore investigated acquisition and memory of fear and fear inhibition in healthy smoking and non-smoking participants (N=349, 22% smokers). We employed a well validated paradigm of context-dependent fear and safety learning (day 1) including a memory retrieval on day 2. During fear learning, a geometrical shape was associated with an aversive electrical stimulation (classical fear conditioning, in danger context) and fear responses were extinguished within another context (extinction learning, in safe context). On day 2, the conditioned stimuli were presented again in both contexts, without any aversive stimulation. Autonomic physiological measurements of skin conductance responses as well as subjective evaluations of fear and expectancy of the aversive stimulation were acquired. We found that impairment of fear inhibition (extinction) in the safe context during learning (day 1) was associated with the amount of pack-years in smokers. During retrieval of fear memories (day 2), smokers showed an impairment of contextual (safety context-related) fear inhibition as compared with non-smokers. These effects were found in physiological as well as subjective measures of fear. We provide initial evidence that smokers as compared with non-smokers show an impairment of fear inhibition. We propose that smokers have a deficit in integrating contextual signs of safety, which is a hallmark of post-traumatic stress and anxiety disorders.

Chronic fluoxetine dissociates contextual from auditory fear memory.

PubMed

Sanders, Jeff; Mayford, Mark

2016-10-06

Fluoxetine is a medication used to treat Major Depressive Disorder and other psychiatric conditions. These experiments studied the effects of chronic fluoxetine treatment on the contextual versus auditory fear memory of mice. We found that chronic fluoxetine treatment of adult mice impaired their contextual fear memory, but spared auditory fear memory. Hippocampal perineuronal nets, which are involved in contextual fear memory plasticity, were unaltered by fluoxetine treatment. These data point to a selective inability to form contextual fear memory as a result of fluoxetine treatment, and they suggest that a blunting of hippocampal-mediated aversive memory may be a therapeutic action for this medication. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila.

PubMed

Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I; Angel, Cristian; Campusano, Jorge M

2015-01-01

The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila.

Boundary Conditions for the Maintenance of Memory by PKM[zeta] in Neocortex

ERIC Educational Resources Information Center

Shema, Reul; Hazvi, Shoshi; Sacktor, Todd C.; Dudai, Yadin

2009-01-01

We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKM[zeta], abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is…

Characterization of the Amplificatory Effect of Norepinephrine in the Acquisition of Pavlovian Threat Associations

ERIC Educational Resources Information Center

Díaz-Mataix, Lorenzo; Piper, Walter T.; Schiff, Hillary C.; Roberts, Clark H.; Campese, Vincent D.; Sears, Robert M.; LeDoux, Joseph E.

2017-01-01

The creation of auditory threat Pavlovian memory requires an initial learning stage in which a neutral conditioned stimulus (CS), such as a tone, is paired with an aversive one (US), such as a shock. In this phase, the CS acquires the capacity of predicting the occurrence of the US and therefore elicits conditioned defense responses.…

Phenotypic transformation affects associative learning in the desert locust.

PubMed

Simões, Patrício M V; Niven, Jeremy E; Ott, Swidbert R

2013-12-02

In desert locusts, increased population densities drive phenotypic transformation from the solitarious to the gregarious phase within a generation [1-4]. Here we show that when presented with odor-food associations, the two extreme phases differ in aversive but not appetitive associative learning, with solitarious locusts showing a conditioned aversion more quickly than gregarious locusts. The acquisition of new learned aversions was blocked entirely in acutely crowded solitarious (transiens) locusts, whereas appetitive learning and prior learned associations were unaffected. These differences in aversive learning support phase-specific feeding strategies. Associative training with hyoscyamine, a plant alkaloid found in the locusts' habitat [5, 6], elicits a phase-dependent odor preference: solitarious locusts avoid an odor associated with hyoscyamine, whereas gregarious locusts do not. Remarkably, when solitarious locusts are crowded and then reconditioned with the odor-hyoscyamine pairing as transiens, the specific blockade of aversive acquisition enables them to override their prior aversive memory with an appetitive one. Under fierce food competition, as occurs during crowding in the field, this provides a neuroecological mechanism enabling locusts to reassign an appetitive value to an odor that they learned previously to avoid. Copyright © 2013 Elsevier Ltd. All rights reserved.

Serotonin is critical for rewarded olfactory short-term memory in Drosophila.

PubMed

Sitaraman, Divya; LaFerriere, Holly; Birman, Serge; Zars, Troy

2012-06-01

The biogenic amines dopamine, octopamine, and serotonin are critical in establishing normal memories. A common view for the amines in insect memory performance has emerged in which dopamine and octopamine are largely responsible for aversive and appetitive memories. Examination of the function of serotonin begins to challenge the notion of one amine type per memory because altering serotonin function also reduces aversive olfactory memory and place memory levels. Could the function of serotonin be restricted to the aversive domain, suggesting a more specific dopamine/serotonin system interaction? The function of the serotonergic system in appetitive olfactory memory was examined. By targeting the tetanus toxin light chain (TNT) and the human inwardly rectifying potassium channel (Kir2.1) to the serotonin neurons with two different GAL4 driver combinations, the serotonergic system was inhibited. Additional use of the GAL80(ts1) system to control expression of transgenes to the adult stage of the life cycle addressed a potential developmental role of serotonin in appetitive memory. Reduction in appetitive olfactory memory performance in flies with these transgenic manipulations, without altering control behaviors, showed that the serotonergic system is also required for normal appetitive memory. Thus, serotonin appears to have a more general role in Drosophila memory, and implies an interaction with both the dopaminergic and octopaminergic systems.

Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

PubMed

Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

2015-12-01

It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

Potent Attenuation of Context Fear by Extinction Training Contiguous with Acquisition

ERIC Educational Resources Information Center

Bernier, Brian E.; Lacagnina, Anthony F.; Drew, Michael R.

2015-01-01

Studies on the behavioral mechanisms underlying contextual fear conditioning (CFC) have demonstrated the importance of preshock context exposure in the formation of aversive context memories. However, there has been comparatively little investigation of the effects of context exposure immediately after the shock. Some models predict that…

Lateral, not medial, prefrontal cortex contributes to punishment and aversive instrumental learning

PubMed Central

Jean-Richard-dit-Bressel, Philip

2016-01-01

Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral agranular insular (RAIC), prelimbic (PL), and infralimbic (IL) cortex in instrumental aversive learning and decision-making. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused mild punishment (punished lever) but continued pressing the other lever that did not cause punishment (unpunished lever). Inactivations of OFC, RAIC, IL, or PL via the GABA agonists baclofen and muscimol (BM) had no effect on the acquisition of instrumental learning. OFC inactivations increased responding on the punished lever during expression of well-learned instrumental aversive learning, whereas RAIC inactivations increased responding on the punished lever when both levers were presented simultaneously in an unpunished choice test. There were few effects of medial PFC (PL and IL) inactivation. These results suggest that lateral PFC, notably OFC and RAIC, have complementary functions in aversive instrumental learning and decision-making; OFC is important for using established aversive instrumental memories to guide behavior away from actions that cause punishment, whereas RAIC is important for aversive decision-making under conditions of choice. PMID:27918280

Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

PubMed

Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

2016-07-01

Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

Behavioural memory reconsolidation of food and fear memories

PubMed Central

Flavell, Charlotte R.; Barber, David J.; Lee, Jonathan L. C.

2012-01-01

The reactivation of a memory through retrieval can render it subject to disruption or modification through the process of memory reconsolidation. In both humans and rodents, briefly reactivating a fear memory results in effective erasure by subsequent extinction training. Here we show that a similar strategy is equally effective in the disruption of appetitive pavlovian cue–food memories. However, systemic administration of the NMDA receptor partial agonist D-cycloserine under the same behavioural conditions did not potentiate appetitive memory extinction, suggesting that reactivation does not enhance subsequent extinction learning. To confirm that reactivation followed by extinction reflects a behavioural analog of memory reconsolidation, we show that prevention of contextual fear memory reactivation by the LVGCC blocker nimodipine interferes with the amnestic outcome. Therefore, the reconsolidation process can be manipulated behaviourally to disrupt both aversive and appetitive memories. PMID:22009036

Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

PubMed Central

Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I.; Angel, Cristian; Campusano, Jorge M.

2015-01-01

The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. PMID:26380118

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

PubMed Central

Kutlu, Munir Gunes

2016-01-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

PubMed

Kutlu, Munir Gunes; Gould, Thomas J

2016-10-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. © 2016 Kutlu and Gould; Published by Cold Spring Harbor Laboratory Press.

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

PubMed

de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

2017-09-01

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of prior aversive experience upon retrograde amnesia induced by hypothermia.

PubMed

Jensen, R A; Riccio, D C; Gehres, L

1975-08-01

Two experiments examined the extent to which retrograde amnesia (RA) is attenuated by prior learning experiences. In Experiment 1, rats initially received either passive avoidance training in a step-through apparatus, exposure to the apparatus, or noncontingent footshock. When training on a second but different passive avoidance task was followed by hypothermia treatment, RA was obtained only in the latter two groups. In Experiment 2, one-way active avoidance training, yoked noncontingent shocks, or apparatus exposure constituted the initial experience. Subsequent step-down passive avoidance training and amnestic treatment resulted in memory loss for the prior apparatus exposure group, but not for either of the preshocked conditions. These experiments demonstrate that certain types of prior aversive experience can substantially modify the magnitude of RA, and, in conjunction with other familiarization studies, emphasize a paradox for interpretations of RA based solely upon CNS disruption. The possibility that hypothermia treatment serves as an important contextual or encoding cue necessary for memory retrieval was considered. It was suggested that prior experience may block RA by enabling rats to differentiate training and treatment conditions.

Differential Regulation of Glutamic Acid Decarboxylase Gene Expression after Extinction of a Recent Memory vs. Intermediate Memory

ERIC Educational Resources Information Center

Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jorg; Pape, Hans-Christian

2012-01-01

Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65…

The roles of Eph receptors in contextual fear conditioning memory formation.

PubMed

Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

2015-10-01

Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

PubMed

Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

2016-04-13

The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal models in which compensatory mechanisms may occur. To avoid these issues, some studies have been done using viral overexpression of PKMζ in different brain structures to show cognitive enhancement. However, electrophysiological experiments were exclusively done in knock-out models or inhibitory studies to show depletion of LTP. There was no study showing the effect of PKMζ overexpression in the hippocampus on behavior and LTP experiments. To our knowledge, this is the first study to combine these aspects with the result of enhanced memory for contextual fear memory and to show enhanced LTP in hippocampal slices overexpressing PKMζ. Copyright © 2016 Schuette et al.

Facilitation of Taste Memory Acquisition by Experiencing Previous Novel Taste Is Protein-Synthesis Dependent

ERIC Educational Resources Information Center

Merhav, Maayan; Rosenblum, Kobi

2008-01-01

Very little is known about the biological and molecular mechanisms that determine the effect of previous experience on implicit learning tasks. In the present study, we first defined weak and strong taste inputs according to measurements in the behavioral paradigm known as latent inhibition of conditioned taste aversion. We then demonstrated that…

Inequity aversion and the evolution of cooperation

NASA Astrophysics Data System (ADS)

Ahmed, Asrar; Karlapalem, Kamalakar

2014-02-01

Evolution of cooperation is a widely studied problem in biology, social science, economics, and artificial intelligence. Most of the existing approaches that explain cooperation rely on some notion of direct or indirect reciprocity. These reciprocity based models assume agents recognize their partner and know their previous interactions, which requires advanced cognitive abilities. In this paper we are interested in developing a model that produces cooperation without requiring any explicit memory of previous game plays. Our model is based on the notion of inequity aversion, a concept introduced within behavioral economics, whereby individuals care about payoff equality in outcomes. Here we explore the effect of using income inequality to guide partner selection and interaction. We study our model by considering both the well-mixed and the spatially structured population and present the conditions under which cooperation becomes dominant. Our results support the hypothesis that inequity aversion promotes cooperative relationship among nonkin.

Inequity aversion and the evolution of cooperation.

PubMed

Ahmed, Asrar; Karlapalem, Kamalakar

2014-02-01

Evolution of cooperation is a widely studied problem in biology, social science, economics, and artificial intelligence. Most of the existing approaches that explain cooperation rely on some notion of direct or indirect reciprocity. These reciprocity based models assume agents recognize their partner and know their previous interactions, which requires advanced cognitive abilities. In this paper we are interested in developing a model that produces cooperation without requiring any explicit memory of previous game plays. Our model is based on the notion of inequity aversion, a concept introduced within behavioral economics, whereby individuals care about payoff equality in outcomes. Here we explore the effect of using income inequality to guide partner selection and interaction. We study our model by considering both the well-mixed and the spatially structured population and present the conditions under which cooperation becomes dominant. Our results support the hypothesis that inequity aversion promotes cooperative relationship among nonkin.

Extinction training during the reconsolidation window prevents recovery of fear.

PubMed

Schiller, Daniela; Raio, Candace M; Phelps, Elizabeth A

2012-08-24

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents the return of fear. Pavlovian fear-conditioning paradigms are commonly employed to create a controlled, novel fear association in the laboratory. After pairing an innocuous stimulus (conditioned stimulus, CS) with an aversive outcome (unconditioned stimulus, US) we can elicit a fear response (conditioned response, or CR) by presenting just the stimulus alone. Once fear is acquired, it can be diminished using extinction training, whereby the conditioned stimulus is repeatedly presented without the aversive outcome until fear is no longer expressed. This inhibitory learning creates a new, safe representation for the CS, which competes for expression with the original fear memory. Although extinction is effective at inhibiting fear, it is not permanent. Fear can spontaneously recover with the passage of time. Exposure to stress or returning to the context of initial learning can also cause fear to resurface. Our protocol addresses the transient nature of extinction by targeting the reconsolidation window to modify emotional memory in a more permanent manner. Ample evidence suggests that reactivating a consolidated memory returns it to a labile state, during which the memory is again susceptible to interference. This window of opportunity appears to open shortly after reactivation and close approximately 6 hrs later, although this may vary depending on the strength and age of the memory. By allowing new information to incorporate into the original memory trace, this memory may be updated as it reconsolidates. Studies involving non-human animals have successfully blocked the expression of fear memory by introducing pharmacological manipulations within the reconsolidation window, however, most agents used are either toxic to humans or show equivocal effects when used in human studies. Our protocol addresses these challenges by offering an effective, yet non-invasive, behavioral manipulation that is safe for humans. By prompting fear memory retrieval prior to extinction, we essentially trigger the reconsolidation process, allowing new safety information (i.e., extinction) to be incorporated while the fear memory is still susceptible to interference. A recent study employing this behavioral manipulation in rats has successfully blocked fear memory using these temporal parameters. Additional studies in humans have demonstrated that introducing new information after the retrieval of previously consolidated motor, episodic, or declarative memories leads to interference with the original memory trace. We outline below a novel protocol used to block fear recovery in humans.

Training-Associated Emotional Arousal Shapes Endocannabinoid Modulation of Spatial Memory Retrieval in Rats.

PubMed

Morena, Maria; De Castro, Valentina; Gray, J Megan; Palmery, Maura; Trezza, Viviana; Roozendaal, Benno; Hill, Matthew N; Campolongo, Patrizia

2015-10-14

Variations in environmental aversiveness influence emotional memory processes in rats. We have previously shown that cannabinoid effects on memory are dependent on the stress level at the time of training as well as on the aversiveness of the environmental context. Here, we investigated whether the hippocampal endocannabinoid system modulates memory retrieval depending on the training-associated arousal level. Male adult Sprague Dawley rats were trained on a water maze spatial task at two different water temperatures (19°C and 25°C) to elicit either higher or lower stress levels, respectively. Rats trained under the higher stress condition had better memory and higher corticosterone concentrations than rats trained at the lower stress condition. The cannabinoid receptor agonist WIN55212-2 (10-30 ng/side), the 2-arachidonoyl glycerol (2-AG) hydrolysis inhibitor JZL184 (0.1-1 μg/side), and the anandamide (AEA) hydrolysis inhibitor URB597 (10-30 ng/side) were administered bilaterally into the hippocampus 60 min before probe-trial retention testing. WIN55212-2 or JZL184, but not URB597, impaired probe-trial performances only of rats trained at the higher stressful condition. Furthermore, rats trained under higher stress levels displayed an increase in hippocampal 2-AG, but not AEA, levels at the time of retention testing and a decreased affinity of the main 2-AG-degrading enzyme for its substrate. The present findings indicate that the endocannabinoid 2-AG in the hippocampus plays a key role in the selective regulation of spatial memory retrieval of stressful experience, shedding light on the neurobiological mechanisms involved in the impact of stress effects on memory processing. Endogenous cannabinoids play a central role in the modulation of memory for emotional events. Here we demonstrate that the endocannabinoid 2-arachidonoylglycerol in the hippocampus, a brain region crucially involved in the regulation of memory processes, selectively modulates spatial memory recall of stressful experiences. Thus, our findings provide evidence that the endocannabinoid 2-arachidonoylglycerol is a key player in mediating the impact of stress on memory retrieval. These findings can pave the way to new potential therapeutic intervention for the treatment of neuropsychiatric disorders, such as post-traumatic stress disorder, where a previous exposure to traumatic events could alter the response to traumatic memory recall leading to mental illness. Copyright © 2015 the authors 0270-6474/15/3513963-13$15.00/0.

Stress promotes generalization of older but not recent threat memories

PubMed Central

Dunsmoor, Joseph E.; Otto, A. Ross; Phelps, Elizabeth A.

2017-01-01

Stress broadly affects the ability to regulate emotions and may contribute to generalization of threat-related behaviors to harmless stimuli. Behavioral generalization also tends to increase over time as memory precision for recent events gives way to more gist-like representations. Thus, acute stress coupled with a delay in time from a negative experience may be a strong predictor of the transition from normal to generalized fear expression. Here, we investigated the effect of a single-episode acute stressor on generalization of aversive learning when stress is administered either immediately after an aversive learning event or following a delay. In a between-subjects design, healthy adult volunteers underwent threat (fear) conditioning using a tone-conditioned stimulus paired with an electric shock to the wrist and another tone not paired with shock. Behavioral generalization was tested to a range of novel tones either on the same day (experiment 1) or 24 h later (experiment 2) and was preceded by either an acute stress induction or a control task. Anticipatory sympathetic arousal [i.e., skin conductance responses (SCRs)] and explicit measures of shock expectancy served as dependent measures. Stress administered shortly after threat conditioning did not affect behavioral generalization. In contrast, stress administered following a delay led to heightened arousal and increased generalization of SCRs and explicit measures of shock expectancy. These findings show that acute stress increases generalization of older but not recent threat memories and have clinical relevance to understanding overgeneralization characteristics of anxiety and stress-related disorders. PMID:28784793

The role of dopamine D2 receptors in the nucleus accumbens during taste-aversive learning and memory extinction after long-term sugar consumption.

PubMed

Miranda, María Isabel; Rangel-Hernández, José Alejandro; Vera-Rivera, Gabriela; García-Medina, Nadia Edith; Soto-Alonso, Gerardo; Rodríguez-García, Gabriela; Núñez-Jaramillo, Luis

2017-09-17

The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. Thus, the objective of this work was to evaluate, after long-term exposure to sugar, the function of dopaminergic D2 receptors in the NAcc core during taste memory retrieval preference test, and during CTA. Adult rats were exposed during 14days to 10% sugar solution as a single liquid ad libitum. NAcc core bilateral injections of D2 dopamine receptor antagonist, haloperidol (1μg/μL), were made before third preference test and CTA acquisition. We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Can an aversive, extinction-resistant memory trigger impairments in walking adaptability? An experimental study using adult rats.

PubMed

Medeiros, Filipe Mello; de Carvalho Myskiw, Jociane; Baptista, Pedro Porto Alegre; Neves, Laura Tartari; Martins, Lucas Athaydes; Furini, Cristiane Regina Guerino; Izquierdo, Iván; Xavier, Léder Leal; Hollands, Kristen; Mestriner, Régis Gemerasca

2018-02-05

Cognitive demands can influence the adaptation of walking, a crucial skill to maintain body stability and prevent falls. Whilst previous research has shown emotional load tunes goal-directed movements, little attention has been given to this finding. This study sought to assess the effects of suffering an extinction-resistant memory on skilled walking performance in adult rats, as an indicator of walking adaptability. Thus, 36 Wistar rats were divided in a two-part experiment. In the first part (n=16), the aversive, extinction-resistance memory paradigm was established using a fear-conditioning chamber. In the second, rats (n=20) were assessed in a neutral room using the ladder rung walking test before and tree days after inducing an extinction-resistance memory. In addition, the elevated plus-maze test was used to control the influence of the anxiety-like status on gait adaptability. Our results revealed the shock group exhibited worse walking adaptability (lower skilled walking score), when compared to the sham group. Moreover, the immobility time in the ladder rung walking test was similar to the controls, suggesting that gait adaptability performance was not a consequence of the fear generalization. No anxiety-like behavior was observed in the plus maze test. Finally, correlation coefficients also showed the skilled walking performance score was positively correlated with the number of gait cycles and trial time in the ladder rung walking test and the total crossings in the plus maze. Overall, these preliminary findings provide evidence to hypothesize an aversive, extinction-resistant experience might change the emotional load, affecting the ability to adapt walking. Copyright © 2017. Published by Elsevier B.V.

Modeling startle eyeblink electromyogram to assess fear learning.

PubMed

Khemka, Saurabh; Tzovara, Athina; Gerster, Samuel; Quednow, Boris B; Bach, Dominik R

2017-02-01

Pavlovian fear conditioning is widely used as a laboratory model of associative learning in human and nonhuman species. In this model, an organism is trained to predict an aversive unconditioned stimulus from initially neutral events (conditioned stimuli, CS). In humans, fear memory is typically measured via conditioned autonomic responses or fear-potentiated startle. For the latter, various analysis approaches have been developed, but a systematic comparison of competing methodologies is lacking. Here, we investigate the suitability of a model-based approach to startle eyeblink analysis for assessment of fear memory, and compare this to extant analysis strategies. First, we build a psychophysiological model (PsPM) on a generic startle response. Then, we optimize and validate this PsPM on three independent fear-conditioning data sets. We demonstrate that our model can robustly distinguish aversive (CS+) from nonaversive stimuli (CS-, i.e., has high predictive validity). Importantly, our model-based approach captures fear-potentiated startle during fear retention as well as fear acquisition. Our results establish a PsPM-based approach to assessment of fear-potentiated startle, and qualify previous peak-scoring methods. Our proposed model represents a generic startle response and can potentially be used beyond fear conditioning, for example, to quantify affective startle modulation or prepulse inhibition of the acoustic startle response. © 2016 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

Mouse model of fragile X syndrome: behavioral and hormonal response to stressors.

PubMed

Nielsen, Darci M; Evans, Jeffrey J; Derber, William J; Johnston, Kenzie A; Laudenslager, Mark L; Crnic, Linda S; Maclean, Kenneth N

2009-06-01

Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity. Copyright (c) 2009 APA, all rights reserved.

Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats.

PubMed

Pedraza, Lizeth K; Sierra, Rodrigo O; Lotz, Fernanda N; Alvares, Lucas de Oliveira

2018-05-08

In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world's most popular psychoactive drugs and its effects on cognitive and mood states are well documented. Nevertheless, the influence of caffeine administration on fear memory processing is not as clear. We employed contextual fear conditioning in rats and acute caffeine administration under a standard memory reconsolidation protocol or periodical memory reactivation. Additionally, potential rewarding/aversion and anxiety effects induced by caffeine were evaluated by conditioning place preference or open field, respectively. Caffeine administration was able to attenuate weak fear memories in a standard memory reconsolidation protocol; however, periodical memory reactivation under caffeine effect was necessary to attenuate strong and remote memories. Moreover, caffeine promoted conditioned place preference and anxiolytic-like behavior, suggesting that caffeine weakens the initial learning during reactivation through counterconditioning mechanisms. Thus, our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory. It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders.

AKAPS Act in a Two-Step Mechanism of Memory Acquisition

PubMed Central

Scheunemann, Lisa; Skroblin, Philipp; Hundsrucker, Christian; Klussmann, Enno; Efetova, Marina

2013-01-01

Defining the molecular and neuronal basis of associative memories is based upon behavioral preparations that yield high performance due to selection of salient stimuli, strong reinforcement, and repeated conditioning trials. One of those preparations is the Drosophila aversive olfactory conditioning procedure where animals initiate multiple memory components after experience of a single cycle training procedure. Here, we explored the analysis of acquisition dynamics as a means to define memory components and revealed strong correlations between particular chronologies of shock impact and number experienced during the associative training situation and subsequent performance of conditioned avoidance. Analyzing acquisition dynamics in Drosophila memory mutants revealed that rutabaga (rut)-dependent cAMP signals couple in a divergent fashion for support of different memory components. In case of anesthesia-sensitive memory (ASM) we identified a characteristic two-step mechanism that links rut-AC1 to A-kinase anchoring proteins (AKAP)-sequestered protein kinase A at the level of Kenyon cells, a recognized center of olfactory learning within the fly brain. We propose that integration of rut-derived cAMP signals at level of AKAPs might serve as counting register that accounts for the two-step mechanism of ASM acquisition. PMID:24174675

Epigenetic mechanisms in fear conditioning: Implications for treating post-traumatic stress disorder

PubMed Central

Kwapis, Janine L.; Wood, Marcelo A.

2014-01-01

Post-traumatic stress disorder (PTSD) and other anxiety disorders stemming from dysregulated fear memory are problematic and costly. Understanding the molecular mechanisms that contribute to the formation and maintenance of these persistent fear associations is critical to developing treatments for PTSD. Epigenetic mechanisms, which control gene expression to produce long-lasting changes in cellular function, may support the formation of fear memory underlying PTSD. Here, we address the role of epigenetic mechanisms in the formation, storage, updating, and extinction of fear memories and discuss methods of targeting these epigenetic mechanisms to reduce the initial formation of fear memory or to enhance its extinction. Epigenetic mechanisms may provide a novel target for pharmaceutical and other treatments to reduce aversive memory contributing to PTSD. PMID:25220045

Impairment of contextual conditioned fear extinction after microinjection of alpha-1-adrenergic blocker prazosin into the medial prefrontal cortex.

PubMed

Do-Monte, Fabrício H M; Allensworth, Melody; Carobrez, Antônio P

2010-07-29

Long-lasting memories of aversive or stressful events have been associated with the noradrenergic system activation. Alpha-1-adrenergic antagonist prazosin has successfully been used in the last years to treat anxiety disorders related to aversive memories recurrence in humans. Contextual conditioned fear extinction paradigm in rats has been used to better understand the mechanisms involved in the attenuation of defensive behaviour after a traumatic situation. Here we investigated the effects of systemic administration of prazosin in the fear extinction processes. Rats were previously paired in a contextual fear conditioning box (1 footshock, 1 mA, 2s duration), further returning to the same box during three consecutive days receiving an intraperitoneal injection of vehicle or prazosin 30 min before (acquisition of extinction; 0.1 or 0.5mg/kg) or immediately after (consolidation of extinction, 0.5 or 1.5mg/kg) each extinction session (10 min). On the last day, all animals were re-exposed undrugged to the apparatus. Since the medial prefrontal cortex (mPFC) has been described as a key structure in the modulation of conditioned fear extinction, the effects of intra-mPFC microinjection (0.2 microl per side) of vehicle (PBS) or prazosin (0.75 or 2.5 nmol) in the acquisition of fear extinction (10 min before extinction session 1) were further evaluated. Subjects were drug-free re-exposed to the same box in the next day (extinction session 2). The percentage of freezing time was used as the memory retention parameter. The results showed that either systemic or intra-mPFC-alpha-1-adrenergic blockade increased the freezing time in the last extinction sessions, suggesting impairment of the extinction of contextual conditioned fear in rats. Copyright 2010 Elsevier B.V. All rights reserved.

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

PubMed Central

Orsini, Caitlin A.; Maren, Stephen

2012-01-01

Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

Memory Trace Reactivation and Behavioral Response during Retrieval Are Differentially Modulated by Amygdalar Glutamate Receptors Activity: Interaction between Amygdala and Insular Cortex

ERIC Educational Resources Information Center

Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko; Bermúdez-Rattoni, Federico

2017-01-01

The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the…

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

PubMed Central

Guimarães Marques, Marcia J.; Reyes-Garcia, Selvin Z.; Marques-Carneiro, José E.; Lopes-Silva, Leonardo B.; Andersen, Monica L.; Cavalheiro, Esper A.; Scorza, Fulvio A.; Scorza, Carla A.

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys, contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys. Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated. PMID:29410617

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil's Amazon Rainforest.

PubMed

Guimarães Marques, Marcia J; Reyes-Garcia, Selvin Z; Marques-Carneiro, José E; Lopes-Silva, Leonardo B; Andersen, Monica L; Cavalheiro, Esper A; Scorza, Fulvio A; Scorza, Carla A

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys , contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys . Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

Aversive olfactory associative memory loses odor specificity over time

PubMed Central

König, Christian; Antwi-Adjei, Emmanuel; Ganesan, Mathangi; Kilonzo, Kasyoka; Viswanathan, Vignesh; Durairaja, Archana; Voigt, Anne

2017-01-01

ABSTRACT Avoiding associatively learned predictors of danger is crucial for survival. Aversive memories can, however, become counter-adaptive when they are overly generalized to harmless cues and contexts. In a fruit fly odor–electric shock associative memory paradigm, we found that learned avoidance lost its specificity for the trained odor and became general to novel odors within a day of training. We discuss the possible neural circuit mechanisms of this effect and highlight the parallelism to over-generalization of learned fear behavior after an incubation period in rodents and humans, with due relevance for post-traumatic stress disorder. PMID:28468811

Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

PubMed Central

Stafford, James M.; Maughan, DeeAnna K.; Ilioi, Elena C.; Lattal, K. Matthew

2013-01-01

An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This extinction process results in the suppression of fear responses, but is generally thought to leave the original fearful memory intact. Here, we investigate the effects of extinction during periods of memory lability on behavioral responses and on expression of the immediate–early gene c-Fos within fear conditioning and extinction circuits. Our results show that long-term extinction is impaired when it occurs during time periods during which the memory should be most vulnerable to disruption (soon after conditioning or retrieval). These behavioral effects are correlated with hyperactivation of medial prefrontal cortex and amygdala subregions associated with fear expression rather than fear extinction. These findings demonstrate that behavioral experiences during periods of heightened fear prevent extinction and prolong the conditioned fear response. PMID:23422280

Learned together, extinguished apart: reducing fear to complex stimuli

PubMed Central

Jones, Carolyn E.; Ringuet, Stephanie; Monfils, Marie-H.

2013-01-01

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window attenuates fear responding and prevents the return of fear in pure tone Pavlovian fear conditioning. Here we sought to examine whether this effect also applies to a more complex fear memory. First, we show that after fear conditioning to the simultaneous presentation of a tone and a light (T+L) coterminating with a shock, the compound memory that ensues is more resistant to fear extinction than simple tone-shock pairings. Next, we demonstrate that the compound memory can be disrupted by interrupting the reconsolidation of the two individual components using a sequential retrieval+extinction paradigm, provided the stronger compound component is retrieved first. These findings provide insight into how compound memories are encoded, and could have important implications for PTSD treatment. PMID:24241750

When fear forms memories: threat of shock and brain potentials during encoding and recognition.

PubMed

Weymar, Mathias; Bradley, Margaret M; Hamm, Alfons O; Lang, Peter J

2013-03-01

The anticipation of highly aversive events is associated with measurable defensive activation, and both animal and human research suggests that stress-inducing contexts can facilitate memory. Here, we investigated whether encoding stimuli in the context of anticipating an aversive shock affects recognition memory. Event-related potentials (ERPs) were measured during a recognition test for words that were encoded in a font color that signaled threat or safety. At encoding, cues signaling threat of shock, compared to safety, prompted enhanced P2 and P3 components. Correct recognition of words encoded in the context of threat, compared to safety, was associated with an enhanced old-new ERP difference (500-700 msec; centro-parietal), and this difference was most reliable for emotional words. Moreover, larger old-new ERP differences when recognizing emotional words encoded in a threatening context were associated with better recognition, compared to words encoded in safety. Taken together, the data indicate enhanced memory for stimuli encoded in a context in which an aversive event is merely anticipated, which could assist in understanding effects of anxiety and stress on memory processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long-term stabilization of place cell remapping produced by a fearful experience

PubMed Central

Wang, Melissa E.; Wann, Ellen G.; Yuan, Robin K.; Ramos Álvarez, Manuel M.; Stead, Squire M.; Muzzio, Isabel A.

2012-01-01

Fear is an emotional response to danger that is highly conserved throughout evolution because it is critical for survival. Accordingly, episodic memory for fearful locations is widely studied using contextual fear conditioning, a hippocampus-dependent task (Kim and Fanselow, 1992; Phillips and LeDoux, 1992). The hippocampus has been implicated in episodic emotional memory and is thought to integrate emotional stimuli within a spatial framework. Physiological evidence supporting the role of the hippocampus in contextual fear indicates that pyramidal cells in this region, which fire in specific locations as an animal moves through an environment, shift their preferred firing locations shortly after the presentation of an aversive stimulus (Moita et al., 2004). However, the long-term physiological mechanisms through which emotional memories are encoded by the hippocampus are unknown. Here we show that during and directly after a fearful experience, new hippocampal representations are established and persist in the long term. We recorded from the same place cells in mouse hippocampal area CA1 over several days during predator odor contextual fear conditioning and found that a subset of cells changed their preferred firing locations in response to the fearful stimulus. Furthermore, the newly formed representations of the fearful context stabilized in the long term. Our results demonstrate that place cells respond to the presence of an aversive stimulus, modify their firing patterns during emotional learning, and stabilize a long-term spatial representation in response to a fearful encounter. The persistent nature of these representations may contribute to the enduring quality of emotional memories. PMID:23136419

Knockout crickets for the study of learning and memory: Dopamine receptor Dop1 mediates aversive but not appetitive reinforcement in crickets.

PubMed

Awata, Hiroko; Watanabe, Takahito; Hamanaka, Yoshitaka; Mito, Taro; Noji, Sumihare; Mizunami, Makoto

2015-11-02

Elucidation of reinforcement mechanisms in associative learning is an important subject in neuroscience. In mammals, dopamine neurons are thought to play critical roles in mediating both appetitive and aversive reinforcement. Our pharmacological studies suggested that octopamine and dopamine neurons mediate reward and punishment, respectively, in crickets, but recent studies in fruit-flies concluded that dopamine neurons mediates both reward and punishment, via the type 1 dopamine receptor Dop1. To resolve the discrepancy between studies in different insect species, we produced Dop1 knockout crickets using the CRISPR/Cas9 system and found that they are defective in aversive learning with sodium chloride punishment but not appetitive learning with water or sucrose reward. The results suggest that dopamine and octopamine neurons mediate aversive and appetitive reinforcement, respectively, in crickets. We suggest unexpected diversity in neurotransmitters mediating appetitive reinforcement between crickets and fruit-flies, although the neurotransmitter mediating aversive reinforcement is conserved. This study demonstrates usefulness of the CRISPR/Cas9 system for producing knockout animals for the study of learning and memory.

An essential memory trace found.

PubMed

Thompson, Richard F

2013-10-01

I argue here that we have succeeded in localizing an essential memory trace for a basic form of associative learning and memory--classical conditioning of discrete responses learned with an aversive stimulus--to the anterior interpositus nucleus of the cerebellum. We first identified the entire essential circuit, using eyelid conditioning as the model system, and used reversible inactivation, during training, of critical structures and pathways to localize definitively the essential memory trace. In recognition of the 30th anniversary of Behavioral Neuroscience, I highlight 1 paper (Tracy, Thompson, Krupa, & Thompson, 1998) that was particularly significant for the progress of this research program. In this review, I present definitive evidence that the essential memory trace for eyelid conditioning is localized to the cerebellum and to no other part of the essential circuit, using electrical stimulation of the pontine nuclei-mossy fibers projecting to the cerebellum as the conditional stimulus (CS; it proved to be a supernormal stimulus resulting in much faster learning than with any peripheral CS) and using an electrical stimulus to the output of the cerebellum as a test, which did not change. Pontine patterns of projection to the cerebellum were confirmed with retrograde labeling techniques. 2013 APA, all rights reserved

The orexin component of fasting triggers memory processes underlying conditioned food selection in the rat.

PubMed

Ferry, Barbara; Duchamp-Viret, Patricia

2014-03-14

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor-malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion of OXA or artificial cerebrospinal fluid (ACSF) 1 h before COA acquisition. An additional group of intact rats were food-deprived for 24 h before acquisition. Results showed that the increased olfactory sensitivity induced by fasting and by OXA infusion was accompanied by enhanced COA performance. The present results suggest that fasting-induced central OXA release influenced COA learning by increasing not only olfactory sensitivity, but also the memory processes underlying the odor-malaise association.

The orexin component of fasting triggers memory processes underlying conditioned food selection in the rat

PubMed Central

Ferry, Barbara; Duchamp-Viret, Patricia

2014-01-01

To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor–malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion of OXA or artificial cerebrospinal fluid (ACSF) 1 h before COA acquisition. An additional group of intact rats were food-deprived for 24 h before acquisition. Results showed that the increased olfactory sensitivity induced by fasting and by OXA infusion was accompanied by enhanced COA performance. The present results suggest that fasting-induced central OXA release influenced COA learning by increasing not only olfactory sensitivity, but also the memory processes underlying the odor–malaise association. PMID:24634353

Effects of endurance, resistance, and concurrent exercise on learning and memory after morphine withdrawal in rats.

PubMed

Zarrinkalam, Ebrahim; Heidarianpour, Ali; Salehi, Iraj; Ranjbar, Kamal; Komaki, Alireza

2016-07-15

Continuous morphine consumption contributes to the development of cognitive disorders. This work investigates the impacts of different types of exercise on learning and memory in morphine-dependent rats. Forty morphine-dependent rats were randomly divided into five groups: sedentary-dependent (Sed-D), endurance exercise-dependent (En-D), strength exercise-dependent (St-D), and combined (concurrent) exercise-dependent (Co-D). Healthy rats were used as controls (Con). After 10weeks of regular exercise (endurance, strength, and concurrent; each five days per week), spatial and aversive learning and memory were assessed using the Morris water maze and shuttle box tests. The results showed that morphine addiction contributes to deficits in spatial learning and memory. Furthermore, each form of exercise training restored spatial learning and memory performance in morphine-dependent rats to levels similar to those of healthy controls. Aversive learning and memory during the acquisition phase were not affected by morphine addiction or exercise, but were significantly decreased by morphine dependence. Only concurrent training returned the time spent in the dark compartment in the shuttle box test to control levels. These findings show that different types of exercise exert similar effects on spatial learning and memory, but show distinct effects on aversive learning and memory. Further, morphine dependence-induced deficits in cognitive function were blocked by exercise. Therefore, different exercise regimens may represent practical treatment methods for cognitive and behavioral impairments associated with morphine-related disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Exposure to a Fearful Context during Periods of Memory Plasticity Impairs Extinction via Hyperactivation of Frontal-Amygdalar Circuits

ERIC Educational Resources Information Center

Stafford, James M.; Maughan, DeeAnna K.; Ilioi, Elena C.; Lattal, K. Matthew

2013-01-01

An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This…

Acute stress impairs the retrieval of extinction memory in humans

PubMed Central

Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.

2014-01-01

Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less extinction retrieval (i.e., greater fear recovery) than those in the control group (n = 25). Our results suggest that acute stress impairs extinction memory retrieval and offers insight into why treatment strategies used in the clinic may be challenging to recruit in daily life where stress is pervasive. PMID:24508065

Carryover effects associated with the single-trial passive avoidance learning task in the young chick.

PubMed

Crowe, Simon F; Hale, Matthew W

2002-09-01

The single-trial passive avoidance task is a useful procedure for examining learning and memory in the young chick. However, it has recently been suggested that discrepant results reported by different laboratories are due to differences in training procedure. The present study investigated a number of parameters surrounding the passive avoidance task, using day-old White Leghorn, Black Australorp cockerels. The results suggested that presentation of a water-dipped bead immediately after the aversive bead significantly altered retention levels. In addition, when the water-dipped bead was presented after the aversive bead, chicks failed to discriminate between beads for a period of 10 min following exposure to the aversant experience. A novel variant of the passive avoidance procedure, involving pretraining with a water-dipped red bead, training with an aversant-coated red bead, and testing with a dry red bead, was evaluated. A measure of avoidance was calculated using all three trials. It is suggested that the use of a single bead, measured both before and after the training experience and using both aversant- and water-trained controls, results in the most concise characterization of memory-related phenomena in the chick which is not contaminated by a carryover effect from the aversive training experience to the nonaversive bead.

Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase.

PubMed

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

2017-05-31

Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Copyright © 2017 the authors 0270-6474/17/375496-•$15.00/0.

An fMRI investigation of the cognitive reappraisal of negative memories

PubMed Central

Holland, Alisha C.; Kensinger, Elizabeth A.

2013-01-01

Episodic memory retrieval can be influenced by individuals’ current goals, including those that are emotional in nature. Participants underwent an fMRI scan while reappraising, or changing the way they thought about aversive images they had previously encoded, to down-regulate (i.e., decrease), up-regulate (i.e., increase), or maintain the emotional intensity associated with their recall. A conjunction analysis between down- and up-regulation during the entire 12-sec recall period revealed that both commonly activated reappraisal-related regions, particularly in the lateral and medial prefrontal cortex (PFC). However, when we analyzed a reappraisal instruction phase prior to recall and then divided the recall phase into the time when individuals were first searching for their memories and later elaborating on their details, we found that down- and up-regulation engaged greater neural activity at different time points. Up-regulation engaged greater PFC activity than down-regulation or maintenance during the reappraisal instruction phase. In contrast, down-regulation engaged greater lateral PFC activity as images were being searched for and retrieved. Maintaining the emotional intensity associated with the aversive images engaged similar regions to a greater extent than either reappraisal condition as participants elaborated on the details of the images they were holding in mind. Our findings suggest that down- and up-regulation engage similar neural regions during memory retrieval, but differ in the timing of this engagement. PMID:23500898

Reappraising social insect behavior through aversive responsiveness and learning.

PubMed

Roussel, Edith; Carcaud, Julie; Sandoz, Jean-Christophe; Giurfa, Martin

2009-01-01

The success of social insects can be in part attributed to their division of labor, which has been explained by a response threshold model. This model posits that individuals differ in their response thresholds to task-associated stimuli, so that individuals with lower thresholds specialize in this task. This model is at odds with findings on honeybee behavior as nectar and pollen foragers exhibit different responsiveness to sucrose, with nectar foragers having higher response thresholds to sucrose concentration. Moreover, it has been suggested that sucrose responsiveness correlates with responsiveness to most if not all other stimuli. If this is the case, explaining task specialization and the origins of division of labor on the basis of differences in response thresholds is difficult. To compare responsiveness to stimuli presenting clear-cut differences in hedonic value and behavioral contexts, we measured appetitive and aversive responsiveness in the same bees in the laboratory. We quantified proboscis extension responses to increasing sucrose concentrations and sting extension responses to electric shocks of increasing voltage. We analyzed the relationship between aversive responsiveness and aversive olfactory conditioning of the sting extension reflex, and determined how this relationship relates to division of labor. Sucrose and shock responsiveness measured in the same bees did not correlate, thus suggesting that they correspond to independent behavioral syndromes, a foraging and a defensive one. Bees which were more responsive to shock learned and memorized better aversive associations. Finally, guards were less responsive than nectar foragers to electric shocks, exhibiting higher tolerance to low voltage shocks. Consequently, foragers, which are more sensitive, were the ones learning and memorizing better in aversive conditioning. Our results constitute the first integrative study on how aversive responsiveness affects learning, memory and social organization in honeybees. We suggest that parallel behavioral modules (e.g. appetitive, aversive) coexist within each individual bee and determine its tendency to adopt a given task. This conclusion, which is at odds with a simple threshold model, should open new opportunities for exploring the division of labor in social insects.

Children's and adults' memory for emotional pictures: examining age-related patterns using the Developmental Affective Photo System.

PubMed

Cordon, Ingrid M; Melinder, Annika M D; Goodman, Gail S; Edelstein, Robin S

2013-02-01

Two studies were conducted to examine theoretical questions about children's and adults' memory for emotional visual stimuli. In Study 1, 7- to 9-year-olds and adults (N=172) participated in the initial creation of the Developmental Affective Photo System (DAPS). Ratings of emotional valence, arousal, and complexity were obtained. In Study 2, DAPS pictures were presented to 20 8- to 12-year-olds and 30 adults, followed by a recognition memory test. Children and adults recognized aversive images better than neutral images. Moreover, children and adults recognized high and moderate arousal images more accurately than low arousal images. Adults' memory for neutral images exceeded that of children, but there were no developmental differences in memory for aversive pictures. Theoretical and methodological implications are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Memory trace reactivation and behavioral response during retrieval are differentially modulated by amygdalar glutamate receptors activity: interaction between amygdala and insular cortex

PubMed Central

Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko

2017-01-01

The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the gustatory zone of the IC during CTA retrieval. Additionally, it has been reported that the amygdala–IC interaction is highly involved in CTA memory establishment. Therefore, we evaluated the effects of infusions of an AMPA receptor antagonist (CNQX) and a NMDA receptor antagonist (APV) into the amygdala on CTA retrieval and IC neurotransmitter levels. Infusion of APV into the amygdala impaired glutamate augmentation within the IC, whereas dopamine and norepinephrine levels augmentation persisted and a reliable CTA expression was observed. Conversely, CNQX infusion into the amygdala impaired the aversion response, as well as norepinephrine and dopamine augmentations in the IC. Interestingly, CNQX infusion did not affect glutamate elevation in the IC. To evaluate the functional meaning of neurotransmitters elevations within the IC on CTA response, we infused specific antagonists for the AMPA, NMDA, D1, and β-adrenergic receptor before retrieval. Results showed that activation of AMPA, D1, and β-adrenergic receptors is necessary for CTA expression, whereas NMDA receptors are not involved in the aversion response. PMID:27980072

Central Ghrelin Resistance Permits the Overconsolidation of Fear Memory.

PubMed

Harmatz, Elia S; Stone, Lauren; Lim, Seh Hong; Lee, Graham; McGrath, Anna; Gisabella, Barbara; Peng, Xiaoyu; Kosoy, Eliza; Yao, Junmei; Liu, Elizabeth; Machado, Nuno J; Weiner, Veronica S; Slocum, Warren; Cunha, Rodrigo A; Goosens, Ki A

2017-06-15

There are many contradictory findings about the role of the hormone ghrelin in aversive processing, with studies suggesting that ghrelin signaling can both inhibit and enhance aversion. Here, we characterize and reconcile the paradoxical role of ghrelin in the acquisition of fearful memories. We used enzyme-linked immunosorbent assay to measure endogenous acyl-ghrelin and corticosterone at time points surrounding auditory fear learning. We used pharmacological (systemic and intra-amygdala) manipulations of ghrelin signaling and examined several aversive and appetitive behaviors. We also used biotin-labeled ghrelin to visualize ghrelin binding sites in coronal brain sections of amygdala. All work was performed in rats. In unstressed rodents, endogenous peripheral acyl-ghrelin robustly inhibits fear memory consolidation through actions in the amygdala and accounts for virtually all interindividual variability in long-term fear memory strength. Higher levels of endogenous ghrelin after fear learning were associated with weaker long-term fear memories, and pharmacological agonism of the ghrelin receptor during the memory consolidation period reduced fear memory strength. These fear-inhibitory effects cannot be explained by changes in appetitive behavior. In contrast, we show that chronic stress, which increases both circulating endogenous acyl-ghrelin and fear memory formation, promotes profound loss of ghrelin binding sites in the amygdala and behavioral insensitivity to ghrelin receptor agonism. These studies provide a new link between stress, a novel type of metabolic resistance, and vulnerability to excessive fear memory formation and reveal that ghrelin can regulate negative emotionality in unstressed animals without altering appetite. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

PubMed

Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

Aversive Memory Reactivation Engages in the Amygdala Only Some Neurotransmitters Involved in Consolidation

ERIC Educational Resources Information Center

Bucherelli, Corrado; Baldi, Elisabetta; Mariottini, Chiara; Passani, Maria Beatrice; Blandina, Patrizio

2006-01-01

Consolidation refers to item stabilization in long-term memory. Retrieval renders a consolidated memory sensitive, and a "reconsolidation" process has been hypothesized to keep the original memory persistent. Some authors could not detect this phenomenon. Here we show that retrieved contextual fear memory is vulnerable to amnesic treatments and…

Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption.

PubMed

Stern, Cristina A J; Gazarini, Lucas; Vanvossen, Ana C; Zuardi, Antonio W; Galve-Roperh, Ismael; Guimaraes, Francisco S; Takahashi, Reinaldo N; Bertoglio, Leandro J

2015-06-01

Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level. We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation. Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples. Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation. Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Interpersonal touch suppresses visual processing of aversive stimuli

PubMed Central

Kawamichi, Hiroaki; Kitada, Ryo; Yoshihara, Kazufumi; Takahashi, Haruka K.; Sadato, Norihiro

2015-01-01

Social contact is essential for survival in human society. A previous study demonstrated that interpersonal contact alleviates pain-related distress by suppressing the activity of its underlying neural network. One explanation for this is that attention is shifted from the cause of distress to interpersonal contact. To test this hypothesis, we conducted a functional MRI (fMRI) study wherein eight pairs of close female friends rated the aversiveness of aversive and non-aversive visual stimuli under two conditions: joining hands either with a rubber model (rubber-hand condition) or with a close friend (human-hand condition). Subsequently, participants rated the overall comfortableness of each condition. The rating result after fMRI indicated that participants experienced greater comfortableness during the human-hand compared to the rubber-hand condition, whereas aversiveness ratings during fMRI were comparable across conditions. The fMRI results showed that the two conditions commonly produced aversive-related activation in both sides of the visual cortex (including V1, V2, and V5). An interaction between aversiveness and hand type showed rubber-hand-specific activation for (aversive > non-aversive) in other visual areas (including V1, V2, V3, and V4v). The effect of interpersonal contact on the processing of aversive stimuli was negatively correlated with the increment of attentional focus to aversiveness measured by a pain-catastrophizing scale. These results suggest that interpersonal touch suppresses the processing of aversive visual stimuli in the occipital cortex. This effect covaried with aversiveness-insensitivity, such that aversive-insensitive individuals might require a lesser degree of attentional capture to aversive-stimulus processing. As joining hands did not influence the subjective ratings of aversiveness, interpersonal touch may operate by redirecting excessive attention away from aversive characteristics of the stimuli. PMID:25904856

Transient inhibition of protein synthesis in the rat insular cortex delays extinction of conditioned taste aversion with cyclosporine A.

PubMed

Hadamitzky, Martin; Orlowski, Kathrin; Schwitalla, Jan Claudius; Bösche, Katharina; Unteroberdörster, Meike; Bendix, Ivo; Engler, Harald; Schedlowski, Manfred

2016-09-01

Conditioned responses gradually weaken and eventually disappear when subjects are repeatedly exposed to the conditioned stimulus (CS) in the absence of the unconditioned stimulus (US), a process called extinction. Studies have demonstrated that extinction of conditioned taste aversion (CTA) can be prevented by interfering with protein synthesis in the insular cortex (IC). However, it remained unknown whether it is possible to pharmacologically stabilize the taste aversive memory trace over longer periods of time. Thus, the present study aimed at investigating the time frame during which extinction of CTA can be efficiently prevented by blocking protein synthesis in the IC. Employing an established conditioning paradigm in rats with saccharin as CS, and the immunosuppressant cyclosporine A (CsA) as US, we show here that daily bilateral intra-insular injections of the protein synthesis inhibitor anisomycin (120μg/μl) immediately after retrieval significantly diminished CTA extinction over a period of five retrieval days and subsequently reached levels of saline-infused controls. These findings demonstrate that it is possible to efficiently delay but not to fully prevent CTA extinction during repeated retrieval trials by blocking protein translation with daily bilateral infusions of anisomycin in the IC. These data confirm and extent earlier reports indicating that the role of protein synthesis in CTA extinction learning is not limited to gastrointestinal malaise-inducing drugs such as lithium chloride (LiCl). Copyright © 2016 Elsevier Inc. All rights reserved.

Mangifera indica extract (Vimang) impairs aversive memory without affecting open field behaviour or habituation in rats.

PubMed

Preissler, Thales; Martins, Márcio Rodrigo; Pardo-Andreu, Gilberto L; Henriques, João Antônio Pêgas; Quevedo, João; Delgado, Rene; Roesler, Rafael

2009-06-01

Vimang is an aqueous extract of Mangifera indica L, used in Cuba for the treatment of immunopathological disorders. Increasing evidence from preclinical studies indicates that Vimang displays antioxidant, antiallergic, analgesic and antiinflammatory actions. The present study investigated the effects of systemic administration of Vimang on behavioural outcomes of neurological function in rats. A single oral administration of Vimang produced an impairment of short- and long-term retention of memory for aversive training when given either 1 h pretraining or immediately posttraining, but not 8 h posttraining. Vimang did not affect open field behaviour or habituation. The results indicate that Vimang might induce deficits of emotionally motivated memory without affecting nonassociative memory, locomotion, exploratory behaviour or anxiety. (c) 2008 John Wiley & Sons, Ltd.

Involvement of BDNF signaling transmission from basolateral amygdala to infralimbic prefrontal cortex in conditioned taste aversion extinction.

PubMed

Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu

2014-05-21

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator. Copyright © 2014 the authors 0270-6474/14/347302-12$15.00/0.

An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

PubMed

Bagatini, Pamela Brambilla; Xavier, Léder Leal; Bertoldi, Karine; Moysés, Felipe; Lovatel, Gisele; Neves, Laura Tartari; Barbosa, Sílvia; Saur, Lisiani; de Senna, Priscylla Nunes; Souto, André Arigony; Siqueira, Ionara Rodrigues; Achaval, Matilde

2017-01-01

The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Conditioned taste aversion and motion sickness in cats and squirrel monkeys

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Corcoran, Meryl Lee; Brizzee, Kenneth R.

1991-01-01

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.

Vitamin D3 Reverses the Hippocampal Cytoskeleton Imbalance But Not Memory Deficits Caused by Ovariectomy in Adult Wistar Rats.

PubMed

Siebert, Cassiana; Pierozan, Paula; Kolling, Janaina; Dos Santos, Tiago Marcon; Sebotaio, Matheus Coimbra; Marques, Eduardo Peil; Biasibetti, Helena; Longoni, Aline; Ferreira, Fernanda; Pessoa-Pureur, Regina; Netto, Carlos Alexandre; Wyse, Angela T S

2017-09-01

The objective of study was to investigate changes caused by ovariectomy (OVX) on aversive and non-aversive memories, as well as on cytoskeleton phosphorylating system and on vitamin D receptor (VDR) immunocontent in hippocampus. The neuroprotective role of vitamin D was also investigated. Ninety-day-old female Wistar rats were divided into four groups: SHAM, OVX, VITAMIN D and OVX + VITAMIN D; 30 days after the OVX, vitamin D supplementation (500 IU/kg), by gavage, for 30 days was started. Results showed that OVX impaired short-term and long-term recognition, and long-term aversive memories. OVX altered hippocampal cytoskeleton phosphorylating system, evidenced by the hyperphosphorylation of glial fibrillary acidic protein (GFAP), low molecular weight neurofilament subunit (NFL), medium molecular weight neurofilament subunit (NFM) and high molecular weight neurofilament subunit (NFH), and increased the immunocontent of c-Jun N-terminal protein kinases (JNK), Ca 2+ /calmodulin-dependent protein kinase II (PKCaMII) and of the sites phosphorylated lysine-serine-proline (KSP) repeats, Ser55 and Ser57. Vitamin D reversed the effects caused by OVX on cytoskeleton in hippocampus, but it was not able to reverse the effects on memory.

Differential effects of cannabinoid receptor agonist on social discrimination and contextual fear in amygdala and hippocampus.

PubMed

Segev, Amir; Akirav, Irit

2011-04-01

We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 µg/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval. In the ventral subiculum (vSub), WIN impaired fear retrieval. In the neutral social discrimination task, WIN into the vSub impaired both acquisition/consolidation and retrieval, whereas in the medial amygdala WIN impaired acquisition. The results suggest that cannabinoid signaling differentially affects memory in a task-, region-, and memory stage-dependent manner.

Reconsolidation or extinction: transcription factor switch in the determination of memory course after retrieval.

PubMed

de la Fuente, Verónica; Freudenthal, Ramiro; Romano, Arturo

2011-04-13

In fear conditioning, aversive stimuli are readily associated with contextual features. A brief reexposure to the training context causes fear memory reconsolidation, whereas a prolonged reexposure induces memory extinction. The regulation of hippocampal gene expression plays a key role in contextual memory consolidation and reconsolidation. However, the mechanisms that determine whether memory will reconsolidate or extinguish are not known. Here, we demonstrate opposing roles for two evolutionarily related transcription factors in the mouse hippocampus. We found that nuclear factor-κB (NF-κB) is required for fear memory reconsolidation. Conversely, calcineurin phosphatase inhibited NF-κB and induced nuclear factor of activated T-cells (NFAT) nuclear translocation in the transition between reconsolidation and extinction. Accordingly, the hippocampal inhibition of both calcineurin and NFAT independently impaired memory extinction, whereas inhibition of NF-κB enhanced memory extinction. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval, supporting a transcriptional switch that directs memory toward reconsolidation or extinction. The precise molecular characterization of postretrieval processes has potential importance to the development of therapeutic strategies for fear memory disorders.

Serotonin affects association of aversive outcomes to past actions.

PubMed

Tanaka, Saori C; Shishida, Kazuhiro; Schweighofer, Nicolas; Okamoto, Yasumasa; Yamawaki, Shigeto; Doya, Kenji

2009-12-16

Impairment in the serotonergic system has been linked to action choices that are less advantageous in a long run. Such impulsive choices can be caused by a deficit in linking a given reward or punishment with past actions. Here, we tested the effect of manipulation of the serotonergic system by tryptophan depletion and loading on learning the association of current rewards and punishments with past actions. We observed slower associative learning when actions were followed by a delayed punishment in the low serotonergic condition. Furthermore, a model-based analysis revealed a positive correlation between the length of the memory trace for aversive choices and subjects' blood tryptophan concentration. Our results suggest that the serotonergic system regulates the time scale of retrospective association of punishments to past actions.

Event-related potential study to aversive auditory stimuli.

PubMed

Czigler, István; Cox, Trevor J; Gyimesi, Kinga; Horváth, János

2007-06-15

In an auditory oddball task emotionally negative (aversive) sounds (e.g. rubbing together of polystyrene) and everyday sounds (e.g. ringing of a bicycle bell) were presented as task-irrelevant (novel) sounds. Both the aversive and the everyday sounds elicited the orientation-related P3a component of the event-related potentials (ERPs). In the 154-250 ms range the ERPs for the aversive sounds were more negative than the ERP of the everyday sounds. For the aversive sounds, this negativity was followed by a frontal positive wave (372-456 ms). The aversive sounds elicited larger late positive shift than the everyday sounds. The early negativity is considered as an initial effect in a broad neural network including limbic structures, while the later is related to the cognitive assessment of the stimuli and to memory-related processes.

The endocannabinoid system and associative learning and memory in zebrafish.

PubMed

Ruhl, Tim; Moesbauer, Kirstin; Oellers, Nadine; von der Emde, Gerhard

2015-09-01

In zebrafish the medial pallium of the dorsal telencephalon represents an amygdala homolog structure, which is crucially involved in emotional associative learning and memory. Similar to the mammalian amygdala, the medial pallium contains a high density of endocannabinoid receptor CB1. To elucidate the role of the zebrafish endocannabinoid system in associative learning, we tested the influence of acute and chronic administration of receptor agonists (THC, WIN55,212-2) and antagonists (Rimonabant, AM-281) on two different learning paradigms. In an appetitively motivated two-alternative choice paradigm, animals learned to associate a certain color with a food reward. In a second set-up, a fish shuttle-box, animals associated the onset of a light stimulus with the occurrence of a subsequent electric shock (avoidance conditioning). Once fish successfully had learned to solve these behavioral tasks, acute receptor activation or inactivation had no effect on memory retrieval, suggesting that established associative memories were stable and not alterable by the endocannabinoid system. In both learning tasks, chronic treatment with receptor antagonists improved acquisition learning, and additionally facilitated reversal learning during color discrimination. In contrast, chronic CB1 activation prevented aversively motivated acquisition learning, while different effects were found on appetitively motivated acquisition learning. While THC significantly improved behavioral performance, WIN55,212-2 significantly impaired color association. Our findings suggest that the zebrafish endocannabinoid system can modulate associative learning and memory. Stimulation of the CB1 receptor might play a more specific role in acquisition and storage of aversive learning and memory, while CB1 blocking induces general enhancement of cognitive functions. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential modulation of changes in hippocampal-septal synaptic excitability by the amygdala as a function of either elemental or contextual fear conditioning in mice.

PubMed

Desmedt, A; Garcia, R; Jaffard, R

1998-01-01

Recent data obtained using a classic fear conditioning paradigm showed a dissociation between the retention of associations relative to contextual information (dependent on the hippocampal formation) and the retention of elemental associations (dependent on the amygdala). Furthermore, it was reported that conditioned emotional responses (CERs) could be dissociated from the recollection of the learning experience (declarative memory) in humans and from modifications of the hippocampal-septal excitability in animals. Our aim was to determine whether these two systems ("behavioral expression" system and "factual memory" system) interact by examining the consequences of amygdalar lesions (1) on the modifications of hippocampal-septal excitability and (2) on the behavioral expression of fear (freezing) resulting from an aversive conditioning during reexposure to conditional stimuli (CSs). During conditioning, to modulate the predictive nature of the context and of a discrete stimulus (tone) on the unconditional stimulus (US) occurrence, the phasic discrete CS was paired with the US or randomly distributed with regard to the US. After the lesion, the CER was dramatically reduced during reexposure to the CSs, whatever the type of acquisition. However, the changes in hippocampal-septal excitability persisted but were altered. For controls, a decrease in septal excitability was observed during reexposure to the conditioning context only for the "unpaired group" (predictive context case). Conversely, among lesioned subjects this decrease was observed in the "paired group" (predictive discrete CS case), whereas this decrease was significantly reduced in the unpaired group with respect to the matched control group. The amplitude and the direction of these modifications suggest a differential modulation of hippocampal-septal excitability by the amygdala to amplify the contribution of the more predictive association signaling the occurrence of the aversive event.

Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity.

PubMed

Santos, Thays B; Céspedes, Isabel C; Viana, Milena B

2014-07-01

Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Adrenergic enhancement of consolidation of object recognition memory.

PubMed

Dornelles, Arethuza; de Lima, Maria Noemia Martins; Grazziotin, Manoela; Presti-Torres, Juliana; Garcia, Vanessa Athaide; Scalco, Felipe Siciliani; Roesler, Rafael; Schröder, Nadja

2007-07-01

Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects. However, previous studies have not examined the effects of EPI on consolidation of recognition memory. Here we report that systemic administration of EPI enhances consolidation of memory for a novel object recognition (NOR) task under different training conditions. Control male rats given a systemic injection of saline (0.9% NaCl) immediately after NOR training showed significant memory retention when tested at 1.5 or 24, but not 96h after training. In contrast, rats given a post-training injection of EPI showed significant retention of NOR at all delays. In a second experiment using a different training condition, rats treated with EPI, but not SAL-treated animals, showed significant NOR retention at both 1.5 and 24-h delays. We next showed that the EPI-induced enhancement of retention tested at 96h after training was prevented by pretraining systemic administration of the beta-adrenoceptor antagonist propranolol. The findings suggest that, as previously observed in experiments using aversively motivated tasks, epinephrine modulates consolidation of recognition memory and that the effects require activation of beta-adrenoceptors.

Requirement of the Combination of Mushroom Body ? Lobe and a/ß Lobes for the Retrieval of Both Aversive and Appetitive Early Memories in "Drosophila"

ERIC Educational Resources Information Center

Xie, Zhiyong; Huang, Cheng; Ci, Bo; Lianzhang, Wang; Zhong, Yi

2013-01-01

Extensive studies of "Drosophila" mushroom body in formation and retrieval of olfactory memories allow us to delineate the functional logic for memory storage and retrieval. Currently, there is a questionable disassociation of circuits for memory storage and retrieval during "Drosophila" olfactory memory processing. Formation…

Reconsolidation Allows Fear Memory to Be Updated to a Less Aversive Level through the Incorporation of Appetitive Information

PubMed Central

Haubrich, Josue; Crestani, Ana P; Cassini, Lindsey F; Santana, Fabiana; Sierra, Rodrigo O; Alvares, Lucas de O; Quillfeldt, Jorge A

2015-01-01

The capacity to adapt to new situations is one of the most important features of memory. When retrieved, memories may undergo a labile state that is sensitive to modification. This process, called reconsolidation, can lead to memory updating through the integration of new information into a previously consolidated memory background. Thus reconsolidation provides the opportunity to modify an undesired fear memory by updating its emotional valence to a less aversive level. Here we evaluated whether a fear memory can be reinterpreted by the concomitant presentation of an appetitive stimulus during its reactivation, hindering fear expression. We found that memory reactivation in the presence of appetitive stimuli resulted in the suppression of a fear response. In addition, fear expression was not amenable to reinstatement, spontaneous recovery, or rapid reacquisition. Such effect was prevented by either systemic injection of nimodipine or intra-hippocampal infusion of ifenprodil, indicating that memory updating was mediated by a reconsolidation mechanism relying on hippocampal neuronal plasticity. Taken together, this study shows that reconsolidation allows for a ‘re-signification' of unwanted fear memories through the incorporation of appetitive information. It brings a new promising cognitive approach to treat fear-related disorders. PMID:25027331

Consumption of an acute dose of caffeine reduces acquisition but not memory in the honey bee.

PubMed

Mustard, Julie A; Dews, Lauren; Brugato, Arlana; Dey, Kevin; Wright, Geraldine A

2012-06-15

Caffeine affects several molecules that are also involved in the processes underlying learning and memory such as cAMP and calcium. However, studies of caffeine's influence on learning and memory in mammals are often contradictory. Invertebrate model systems have provided valuable insight into the actions of many neuroactive compounds including ethanol and cocaine. We use the honey bee (Apis mellifera) to investigate how the ingestion of acute doses of caffeine before, during, and after conditioning influences performance in an appetitive olfactory learning and memory task. Consumption of caffeine doses of 0.01 M or greater during or prior to conditioning causes a significant reduction in response levels during acquisition. Although bees find the taste of caffeine to be aversive at high concentrations, the bitter taste does not explain the reduction in acquisition observed for bees fed caffeine before conditioning. While high doses of caffeine reduced performance during acquisition, the response levels of bees given caffeine were the same as those of the sucrose only control group in a recall test 24h after conditioning. In addition, caffeine administered after conditioning had no affect on recall. These results suggest that caffeine specifically affects performance during acquisition and not the processes involved in the formation of early long term memory. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.

PubMed

Manwell, Laurie A; Mallet, Paul E

2015-05-01

Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA). The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined. Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials. Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses. These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

PubMed Central

Besnard, Antoine; Sahay, Amar

2016-01-01

The generalization of fear is an adaptive, behavioral, and physiological response to the likelihood of threat in the environment. In contrast, the overgeneralization of fear, a cardinal feature of posttraumatic stress disorder (PTSD), manifests as inappropriate, uncontrollable expression of fear in neutral and safe environments. Overgeneralization of fear stems from impaired discrimination of safe from aversive environments or discernment of unlikely threats from those that are highly probable. In addition, the time-dependent erosion of episodic details of traumatic memories might contribute to their generalization. Understanding the neural mechanisms underlying the overgeneralization of fear will guide development of novel therapeutic strategies to combat PTSD. Here, we conceptualize generalization of fear in terms of resolution of interference between similar memories. We propose a role for a fundamental encoding mechanism, pattern separation, in the dentate gyrus (DG)–CA3 circuit in resolving interference between ambiguous or uncertain threats and in preserving episodic content of remote aversive memories in hippocampal–cortical networks. We invoke cellular-, circuit-, and systems-based mechanisms by which adult-born dentate granule cells (DGCs) modulate pattern separation to influence resolution of interference and maintain precision of remote aversive memories. We discuss evidence for how these mechanisms are affected by stress, a risk factor for PTSD, to increase memory interference and decrease precision. Using this scaffold we ideate strategies to curb overgeneralization of fear in PTSD. PMID:26068726

Differential Dynamics of Amino Acid Release in the Amygdala and Olfactory Cortex during Odor Fear Acquisition as Revealed with Simultaneous High Temporal Resolution Microdialysis

ERIC Educational Resources Information Center

Hegoburu, Chloe; Sevelinges, Yannick; Thevenet, Marc; Gervais, Remi; Parrot, Sandrine; Mouly, Anne-Marie

2009-01-01

Although the amygdala seems to be essential to the formation and storage of fear memories, it might store only some aspects of the aversive event and facilitate the storage of more specific sensory aspects in cortical areas. We addressed the time course of amygdala and cortical activation in the context of odor fear conditioning in rats. Using…

Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.

PubMed

Kim, Woong Bin; Cho, Jun-Hyeong

2017-08-30

In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

Examining Relationships between Executive Functioning and Delay Aversion in Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Karalunas, Sarah L.; Huang-Pollock, Cynthia L.

2011-01-01

Although motivation and cognition are often examined separately, recent theory suggests that a delay-averse motivational style may negatively impact development of executive functions (EFs), such as working memory (WM) and response inhibition (RI) for children with Attention Deficit Hyperactivity Disorder (ADHD; Sonuga-Barke, 2002). This model…

DAT genotype modulates striatal processing and long-term memory for items associated with reward and punishment☆

PubMed Central

Wittmann, Bianca C.; Tan, Geoffrey C.; Lisman, John E.; Dolan, Raymond J.; Düzel, Emrah

2013-01-01

Previous studies have shown that appetitive motivation enhances episodic memory formation via a network including the substantia nigra/ventral tegmental area (SN/VTA), striatum and hippocampus. This functional magnetic resonance imaging (fMRI) study now contrasted the impact of aversive and appetitive motivation on episodic long-term memory. Cue pictures predicted monetary reward or punishment in alternating experimental blocks. One day later, episodic memory for the cue pictures was tested. We also investigated how the neural processing of appetitive and aversive motivation and episodic memory were modulated by dopaminergic mechanisms. To that end, participants were selected on the basis of their genotype for a variable number of tandem repeat polymorphism of the dopamine transporter (DAT) gene. The resulting groups were carefully matched for the 5-HTTLPR polymorphism of the serotonin transporter gene. Recognition memory for cues from both motivational categories was enhanced in participants homozygous for the 10-repeat allele of the DAT, the functional effects of which are not known yet, but not in heterozygous subjects. In comparison with heterozygous participants, 10-repeat homozygous participants also showed increased striatal activity for anticipation of motivational outcomes compared to neutral outcomes. In a subsequent memory analysis, encoding activity in striatum and hippocampus was found to be higher for later recognized items in 10-repeat homozygotes compared to 9/10-repeat heterozygotes. These findings suggest that processing of appetitive and aversive motivation in the human striatum involve the dopaminergic system and that dopamine plays a role in memory for both types of motivational information. In accordance with animal studies, these data support the idea that encoding of motivational events depends on dopaminergic processes in the hippocampus. PMID:23911780

Modeling fear‐conditioned bradycardia in humans

PubMed Central

Tzovara, Athina; Staib, Matthias; Paulus, Philipp C.; Hofer, Nicolas; Bach, Dominik R.

2016-01-01

Abstract Across species, cued fear conditioning is a common experimental paradigm to investigate aversive Pavlovian learning. While fear‐conditioned stimuli (CS+) elicit overt behavior in many mammals, this is not the case in humans. Typically, autonomic nervous system activity is used to quantify fear memory in humans, measured by skin conductance responses (SCR). Here, we investigate whether heart period responses (HPR) evoked by the CS, often observed in humans and small mammals, are suitable to complement SCR as an index of fear memory in humans. We analyze four datasets involving delay and trace conditioning, in which heart beats are identified via electrocardiogram or pulse oximetry, to show that fear‐conditioned heart rate deceleration (bradycardia) is elicited and robustly distinguishes CS+ from CS−. We then develop a psychophysiological model (PsPM) of fear‐conditioned HPR. This PsPM is inverted to yield estimates of autonomic input into the heart. We show that the sensitivity to distinguish CS+ and CS− (predictive validity) is higher for model‐based estimates than peak‐scoring analysis, and compare this with SCR. Our work provides a novel tool to investigate fear memory in humans that allows direct comparison between species. PMID:26950648

Sleep restores behavioral plasticity to Drosophila mutants

PubMed Central

Dissel, Stephane; Angadi, Veena; Kirszenblat, Leonie; Suzuki, Yasuko; Donlea, Jeff; Klose, Markus; Koch, Zachary; English, Denis; Winsky-Sommerer, Raphaelle; van Swinderen, Bruno; Shaw, Paul J.

2015-01-01

SUMMARY Given the role that sleep plays in modulating plasticity, we hypothesized that increasing sleep would restore memory to canonical memory mutants without specifically rescuing the causal molecular-lesion. Sleep was increased using three independent strategies: activating the dorsal Fan Shaped Body (FB), increasing the expression of Fatty acid binding protein (dFabp) or by administering the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP). Short-term memory (STM) or Long-term memory (LTM) was evaluated in rutabaga (rut) and dunce (dnc) mutants using Aversive Phototaxic Suppression (APS) and courtship conditioning. Each of the three independent strategies increased sleep and restored memory to rut and dnc mutants. Importantly, inducing sleep also reverses memory defects in a Drosophila model of Alzheimer’s disease. Together these data demonstrate that sleep plays a more fundamental role in modulating behavioral plasticity than previously appreciated and suggests that increasing sleep may benefit patients with certain neurological disorders. PMID:25913403

Green tea and cocoa enhance cognition in Lymnaea

PubMed Central

Swinton, Erin; de Freitas, Emily; Swinton, Cayley; Shymansky, Tamila; Hiles, Emily; Zhang, Jack; Rothwell, Cailin; Lukowiak, Ken

2018-01-01

ABSTRACT A flavonoid, (-)-epicatechi (Epi), enhances long-term memory (LTM) formation in Lymnaea and reverses memory obstruction caused by stress. Many foods contain substantial amounts of Epi, (e.g. green tea and cocoa). In humans eating such foods may directly or indirectly enhance cognition. We directly test whether operant conditioning training Lymnaea in these natural foods result in the same effects as training snails in pure Epi. We found that exposure to products containing high concentrations of Epi (e.g. green tea and cocoa) during training enhanced memory formation and could even reverse a learning and memory deficit brought about by stress. Epi can be photo-inactivated by exposure to ultraviolet light. We found that following photo-inactivation of Epi, memory enhancement did not occur. Photo-inactivation of foods containing Epi (e,g. green tea) blocked their ability to enhance LTM. Our data are thus consistent with the hypothesis that dietary sources of Epi can have positive benefits on cognitive ability and be able to reverse memory aversive states. PMID:29497476

Intra-Amygdala Injections of CREB Antisense Impair Inhibitory Avoidance Memory: Role of Norepinephrine and Acetylcholine

ERIC Educational Resources Information Center

Canal, Clinton E.; Chang, Qing; Gold, Paul E.

2008-01-01

Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed…

CREB regulates memory allocation in the insular cortex

PubMed Central

Sano, Yoshitake; Shobe, Justin L.; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J.; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J.

2016-01-01

Summary The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory [1, 2]. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cAMP response element binding protein (CREB) are more likely to be recruited into encoding and storing fear memory [3–6]. To determine whether specific mechanisms also regulate memory allocation in other brain regions, and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (CS) with the experience of malaise (such as that induced by LiCl; US). The insular cortex is required for CTA memory formation and retrieval [7–12]. CTA learning activates a subpopulation of neurons in this structure [13–15], and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation [16, 17]. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc Fluorescence In Situ Hybridization (FISH) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory. PMID:25454591

Active avoidance learning requires prefrontal suppression of amygdala-mediated defensive reactions.

PubMed

Moscarello, Justin M; LeDoux, Joseph E

2013-02-27

Signaled active avoidance (AA) paradigms train subjects to prevent an aversive outcome by performing a learned behavior during the presentation of a conditioned cue. This complex form of conditioning involves pavlovian and instrumental components, which produce competing behavioral responses that must be reconciled for the subject to successfully avoid an aversive stimulus. In signaled AA paradigm for rat, we tested the hypothesis that the instrumental component of AA training recruits infralimbic prefrontal cortex (ilPFC) to inhibit central amygdala (CeA)-mediated Pavlovian reactions. Pretraining lesions of ilPFC increased conditioned freezing while causing a corresponding decrease in avoidance; lesions of CeA produced opposite effects, reducing freezing and facilitating avoidance behavior. Pharmacological inactivation experiments demonstrated that ilPFC is relevant to both acquisition and expression phases of AA learning. Inactivation experiments also revealed that AA produces an ilPFC-mediated diminution of pavlovian reactions that extends beyond the training context, even when the conditioned stimulus is presented in an environment that does not allow the avoidance response. Finally, injection of a protein synthesis inhibitor into either ilPFC or CeA impaired or facilitated AA, respectively, showing that avoidance training produces two opposing memory traces in these regions. These data support a model in which AA learning recruits ilPFC to inhibit CeA-mediated defense behaviors, leading to a robust suppression of freezing that generalizes across environments. Thus, ilPFC functions as an inhibitory interface, allowing instrumental control over an aversive outcome to attenuate the expression of freezing and other reactions to conditioned threat.

Disruption of medial septum and diagonal bands of Broca cholinergic projections to the ventral hippocampus disrupt auditory fear memory.

PubMed

Staib, Jennifer M; Della Valle, Rebecca; Knox, Dayan K

2018-07-01

In classical fear conditioning, a neutral conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US), which leads to a fear memory. If the CS is repeatedly presented without the US after fear conditioning, the formation of an extinction memory occurs, which inhibits fear memory expression. A previous study has demonstrated that selective cholinergic lesions in the medial septum and vertical limb of the diagonal bands of Broca (MS/vDBB) prior to fear and extinction learning disrupt contextual fear memory discrimination and acquisition of extinction memory. MS/vDBB cholinergic neurons project to a number of substrates that are critical for fear and extinction memory. However, it is currently unknown which of these efferent projections are critical for contextual fear memory discrimination and extinction memory. To address this, we induced cholinergic lesions in efferent targets of MS/vDBB cholinergic neurons. These included the dorsal hippocampus (dHipp), ventral hippocampus (vHipp), medial prefrontal cortex (mPFC), and in the mPFC and dHipp combined. None of these lesion groups exhibited deficits in contextual fear memory discrimination or extinction memory. However, vHipp cholinergic lesions disrupted auditory fear memory. Because MS/vDBB cholinergic neurons are the sole source of acetylcholine in the vHipp, these results suggest that MS/vDBB cholinergic input to the vHipp is critical for auditory fear memory. Taken together with previous findings, the results of this study suggest that MS/vDBB cholinergic neurons are critical for fear and extinction memory, though further research is needed to elucidate the role of MS/vDBB cholinergic neurons in these types of emotional memory. Copyright © 2018 Elsevier Inc. All rights reserved.

Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

ERIC Educational Resources Information Center

Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

2006-01-01

The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

High working memory load impairs the effect of cognitive reappraisal on emotional response: Evidence from an event-related potential study.

PubMed

Gan, Shuzhen; Yang, Jianfeng; Chen, Xuhai; Zhang, Xiuping; Yang, Yufang

2017-02-03

This study investigates how the working memory (WM) load influenced the efficacy of cognitive reappraisal, a frequently used strategy for emotion regulation. In a dual-task paradigm, the participants were required to perform a high-load or a low-load memory task and simultaneously reappraise aversive pictures with a negative or a neutral meaning. In the low-load condition, we found that the amplitude of emotion-enhanced late positive potential (LPP) was significantly decreased by neutral reappraisal compared to negative reappraisal. In the high-load condition, this regulatory effect of reappraisal disappeared. These results suggest that successful reappraisal relies on cognitive resources and WM processes. If the necessary resources involved in reappraisal are over-depleted by a concurrent memory task, the reappraisal effect will be impaired. Moreover, we found that emotion-enhanced LPP was significant in both of the high-load and low-load tasks, which suggests that emotional electrocortical response may not be susceptible to the available resources. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

PubMed

Azambuja, Amanda Stapenhorst; Correa, Lilian; Gabiatti, Bernardo Pappi; Martins, Giselle Renata; de Oliveira Franco, Álvaro; Ribeiro, Maria Flávia Marques; Baldo, Guilherme

2018-02-01

Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

Memory Retrieval Re-Activates Erk1/2 Signaling in the Same Set of CA1 Neurons Recruited During Conditioning.

PubMed

Zamorano, Cristina; Fernández-Albert, Jordi; Storm, Daniel R; Carné, Xavier; Sindreu, Carlos

2018-02-01

The hippocampus enables a range of behaviors through its intrinsic circuits and concerted actions with other brain regions. One such important function is the retrieval of episodic memories. How hippocampal cells support retrieval of contextual fear memory remains largely unclear. Here we monitored phospho-activation of extracellular-regulated kinase (Erk1/2) across neuronal populations of the hippocampus to find that CA1 pyramidal neurons, but not cells in CA3 or dentate gyrus, specifically respond to retrieval of an aversive context. In contrast, retrieval of a neutral context that fails to elicit a threat response did not activate Erk1/2. Moreover, retrieval preferentially re-activated Erk1/2 in the same set of CA1 neurons previously activated during conditioning in a context-specific manner. By confining drug inhibition within dorsal CA1, we established the crucial role for Erk1/2 activity in retrieval of long-term memory, as well as in amygdala activation associated with fear expression. These data provide functional evidence that Erk1/2 signaling in CA1 encodes a specific neural representation of contextual memory with emotional value. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Fear Conditioning in an Abdominal Pain Model: Neural Responses during Associative Learning and Extinction in Healthy Subjects

PubMed Central

Kattoor, Joswin; Gizewski, Elke R.; Kotsis, Vassilios; Benson, Sven; Gramsch, Carolin; Theysohn, Nina; Maderwald, Stefan; Forsting, Michael; Schedlowski, Manfred; Elsenbruch, Sigrid

2013-01-01

Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy humans, visual conditioned stimuli (CS+) were paired with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS−) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, conditioned anticipatory neural activation was assessed along with perceived CS-US contingency and CS unpleasantness. Fear conditioning resulted in significant contingency awareness and valence change, i.e., learned unpleasantness of a previously neutral stimulus. This was paralleled by anticipatory activation of the anterior cingulate cortex, the somatosensory cortex and precuneus (all during early acquisition) and the amygdala (late acquisition) in response to the CS+. During extinction, anticipatory activation of the dorsolateral prefrontal cortex to the CS− was observed. In the reinstatement phase, a tendency for parahippocampal activation was found. Fear conditioning with rectal pain stimuli is feasible and leads to learned unpleasantness of previously neutral stimuli. Within the brain, conditioned anticipatory activations are seen in core areas of the central fear network including the amygdala and the anterior cingulate cortex. During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during reinstatement could indicate a reactivation of the old memory trace. Together, these findings contribute to our understanding of aversive visceral learning and memory processes relevant to the pathophysiology of chronic abdominal pain. PMID:23468832

Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

PubMed

McNay, E C; Gold, P E

1998-05-15

Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

Bidirectional switch of the valence associated with a hippocampal contextual memory engram.

PubMed

Redondo, Roger L; Kim, Joshua; Arons, Autumn L; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu

2014-09-18

The valence of memories is malleable because of their intrinsic reconstructive property. This property of memory has been used clinically to treat maladaptive behaviours. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell- manipulation technique. We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that although the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new unconditioned stimulus of an opposite valence. Our present work provides new insight into the functional neural circuits underlying the malleability of emotional memory.

Bidirectional switch of the valence associated with a hippocampal contextual memory engram

PubMed Central

Redondo, Roger L; Kim, Joshua; Arons, Autumn L; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu

2014-01-01

The valence of memories is malleable because of their intrinsic reconstructive property1. This property of memory has been used clinically to treat maladaptive behaviours2. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here, we investigated these mechanisms by applying the recently developed memory engram cell-labelling and -manipulation technique 3,4. We labelled, with Channelrhodopsin-2 (ChR2), a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that while the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new US of an opposite valence. Our present work provides new insight into the functional neural circuit underlying the malleability of emotional memory. PMID:25162525

Reflecting on imagery: a clinical perspective and overview of the special issue of memory on mental imagery and memory in psychopathology.

PubMed

Hackmann, Ann; Holmes, Emily A

2004-07-01

The authors provide an overview of the papers in the special issue of Memory on mental imagery and memory in psychopathology. The papers address emotional, intrusive mental imagery across a range of psychological disorders including post-traumatic stress disorder (PTSD), agoraphobia, body dysmorphic disorder, mood disorders, and psychosis. They include work on information processing issues including modelling cravings, conditioning, and aversions, as well as imagery qualities such as vividness and emotionality. The overview aims to place the articles in a broader context and draw out some exciting implications of this novel work. It provides a clinical context to the recent growth in this area from a cognitive behavioural therapy (CBT) perspective. We begin with PTSD, and consider links to imagery in other disorders. The clinical implications stemming from this empirical work and from autobiographical memory theory are discussed. These include consideration of a variety of techniques for eliminating troublesome imagery, and creating healthy, realistic alternatives.

Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

PubMed

de Quervain, Dominique J-F; Margraf, Jürgen

2008-04-07

Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of glucocorticoids in the treatment of anxiety disorders and to explore the potential of combining glucocorticoid treatment with psychotherapy.

Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

ERIC Educational Resources Information Center

Segev, Amir; Akirav, Irit

2011-01-01

We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

Appetitive but Not Aversive Olfactory Conditioning Modifies Antennal Movements in Honeybees

ERIC Educational Resources Information Center

Cholé, Hanna; Junca, Pierre; Sandoz, Jean-Christophe

2015-01-01

In honeybees, two olfactory conditioning protocols allow the study of appetitive and aversive Pavlovian associations. Appetitive conditioning of the proboscis extension response (PER) involves associating an odor, the conditioned stimulus (CS) with a sucrose solution, the unconditioned stimulus (US). Conversely, aversive conditioning of the sting…

Enhancing effects of lithium on memory are not by-products of learning or attentional deficits.

PubMed

Tsaltas, Eleftheria; Kyriazi, Theodora; Poulopoulou, Cornelia; Kontis, Dimitrios; Maillis, Antonios

2007-06-18

We recently reported that chronic lithium (LiCl), at therapeutic plasma levels, enhanced spatial working memory and retention of an aversive contingency. Here we examine the possibility that these effects be secondary to LiCl effects on the ability to ignore irrelevant stimuli or on fear conditioning. In Experiment 1, rats subjected to >30 daily intraperitoneal injections of LiCl (2mmol/kg) or saline underwent conditioned emotional response training (CER: 2 CS pairings with 1-s, 1-mA shock) after 40 pre-exposures either to the CS (latent inhibition-LiCl/latent inhibition-saline, n=8) or to another stimulus (control-LiCl/control-saline, n=8). In Experiment 2, eight LiCl and eight saline animals were trained in on-the-baseline (VI-60s) CER (1-s, 0.15-mA shock in CS-signalled periods) in the Skinner box. In Experiment 1, LiCl animals showed normal latent inhibition. In both experiments, their fear conditioning was unimpaired. Therefore, the previously reported memory improvement under chronic lithium cannot be attributed to changes in the ability to ignore irrelevant stimuli or in fear conditioning.

Prefrontal consolidation supports the attainment of fear memory accuracy

PubMed Central

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. PMID:25031365

Persistent increased PKMζ in long-term and remote spatial memory.

PubMed

Hsieh, Changchi; Tsokas, Panayiotis; Serrano, Peter; Hernández, A Iván; Tian, Dezhi; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2017-02-01

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance. Copyright © 2016. Published by Elsevier Inc.

Differences in Risk Aversion between Young and Older Adults.

PubMed

Albert, Steven M; Duffy, John

2012-01-15

Research on decision-making strategies among younger and older adults suggests that older adults may be more risk averse than younger people in the case of potential losses. These results mostly come from experimental studies involving gambling paradigms. Since these paradigms involve substantial demands on memory and learning, differences in risk aversion or other features of decision-making attributed to age may in fact reflect age-related declines in cognitive abilities. In the current study, older and younger adults completed a simpler, paired lottery choice task used in the experimental economics literature to elicit risk aversion. A similar approach was used to elicit participants' discount rates. The older adult group was more risk averse than younger adults (p < .05) and also had a higher discount rate (15.6-21.0% vs. 10.3-15.5%, p < .01), indicating lower expected utility from future income. Risk aversion and implied discount rates were weakly correlated. It may be valuable to investigate developmental changes in neural correlates of decision-making across the lifespan.

Differences in Risk Aversion between Young and Older Adults

PubMed Central

Albert, Steven M.; Duffy, John

2013-01-01

Research on decision-making strategies among younger and older adults suggests that older adults may be more risk averse than younger people in the case of potential losses. These results mostly come from experimental studies involving gambling paradigms. Since these paradigms involve substantial demands on memory and learning, differences in risk aversion or other features of decision-making attributed to age may in fact reflect age-related declines in cognitive abilities. In the current study, older and younger adults completed a simpler, paired lottery choice task used in the experimental economics literature to elicit risk aversion. A similar approach was used to elicit participants' discount rates. The older adult group was more risk averse than younger adults (p < .05) and also had a higher discount rate (15.6-21.0% vs. 10.3-15.5%, p < .01), indicating lower expected utility from future income. Risk aversion and implied discount rates were weakly correlated. It may be valuable to investigate developmental changes in neural correlates of decision-making across the lifespan. PMID:24319671

Stress Response Recruits the Hippocampal Endocannabinoid System for the Modulation of Fear Memory

ERIC Educational Resources Information Center

Alvares, Lucas de Oliveira; Engelke, Douglas Senna; Diehl, Felipe; Scheffer-Teixeira, Robson; Haubrich, Josue; Cassini, Lindsey de Freitas; Molina, Victor Alejandro; Quillfeldt, Jorge Alberto

2010-01-01

The modulation of memory processes is one of the several functions of the endocannabinoid system (ECS) in the brain, with CB1 receptors highly expressed in areas such as the dorsal hippocampus. Experimental evidence suggested an important role of the ECS in aversively motivated memories. Similarly, glucocorticoids released in response to stress…

Opposite Actions of Dopamine on Aversive and Appetitive Memories in the Crab

ERIC Educational Resources Information Center

Klappenbach, Martin; Maldonado, Hector; Locatelli, Fernando; Kaczer, Laura

2012-01-01

The understanding of how the reinforcement is represented in the central nervous system during memory formation is a current issue in neurobiology. Several studies in insects provide evidence of the instructive role of biogenic amines during the learning and memory process. In insects it was widely accepted that dopamine (DA) mediates aversive…

Reactivation-Dependent Amnesia for Appetitive Memories Is Determined by the Contingency of Stimulus Presentation

ERIC Educational Resources Information Center

Lee, Jonathan L. C.; Everitt, Barry J.

2008-01-01

Previously acquired aversive and appetitive memories are not stable and permanent. The reactivation of such memories by re-exposure to training stimuli renders them vulnerable to disruption by amnestic agents such as the noncompetitive N-methyl-"D"-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-"SH"-dibenzo{a,d}cyclohepten-5,10imine…

Do executive deficits and delay aversion make independent contributions to preschool attention-deficit/hyperactivity disorder symptoms?

PubMed

Sonuga-Barke, Edmund J S; Dalen, Lindy; Remington, Bob

2003-11-01

To test whether deficits in executive function and delay aversion make independent contributions to levels of attention-deficit/hyperactivity disorder (ADHD) symptoms exhibited by preschool children. One hundred fifty-six children between 3 and 5.5 years old (78 girls and 78 boys) selected from the community completed an age-appropriate battery of tests measuring working memory, set shifting, planning, delay of gratification, and preference for delayed rewards. Parents completed a clinical interview about their children's ADHD symptoms. Analysis of test performance revealed two factors: executive dysfunction and delay aversion. Multivariate analysis demonstrated that when other factors (i.e., age, IQ, and conduct problems) were controlled, executive dysfunction and delay aversion each made significant independent contributions to predictions of ADHD symptoms. Preschool ADHD symptoms are psychologically heterogeneous. Executive dysfunction and delay aversion may represent two distinct and early appearing neurodevelopmental bases for ADHD symptoms.

A kinase-dependent feedforward loop affects CREBB stability and long term memory formation.

PubMed

Lee, Pei-Tseng; Lin, Guang; Lin, Wen-Wen; Diao, Fengqiu; White, Benjamin H; Bellen, Hugo J

2018-02-23

In Drosophila , long-term memory (LTM) requires the cAMP-dependent transcription factor CREBB, expressed in the mushroom bodies (MB) and phosphorylated by PKA. To identify other kinases required for memory formation, we integrated Trojan exons encoding T2A-GAL4 into genes encoding putative kinases and selected for genes expressed in MB. These lines were screened for learning/memory deficits using UAS-RNAi knockdown based on an olfactory aversive conditioning assay. We identified a novel, conserved kinase, Meng-Po ( MP , CG11221 , SBK1 in human), the loss of which severely affects 3 hr memory and 24 hr LTM, but not learning. Remarkably, memory is lost upon removal of the MP protein in adult MB but restored upon its reintroduction. Overexpression of MP in MB significantly increases LTM in wild-type flies showing that MP is a limiting factor for LTM. We show that PKA phosphorylates MP and that both proteins synergize in a feedforward loop to control CREBB levels and LTM. key words: Drosophila, Mushroom bodies, SBK1, deGradFP, T2A-GAL4, MiMIC.

Contextual fear conditioning in zebrafish.

PubMed

Kenney, Justin W; Scott, Ian C; Josselyn, Sheena A; Frankland, Paul W

2017-10-01

Zebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects of learning and memory in adult fish. Here, we describe the development of a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by an established amnestic agent (MK-801), lasts at least 14 d, and exhibits extinction. Furthermore, fish of various background strains (AB, Tu, and TL) are able to acquire fear conditioning, but differ in fear extinction rates. Taken together, we find that contextual fear conditioning in zebrafish shares many similarities with the widely used contextual fear conditioning paradigm in rodents. Combined with the amenability of genetic manipulation in zebrafish, we anticipate that our paradigm will prove to be a useful complementary system in which to examine the molecular basis of vertebrate learning and memory. © 2017 Kenney et al.; Published by Cold Spring Harbor Laboratory Press.

Prefrontal Consolidation Supports the Attainment of Fear Memory Accuracy

ERIC Educational Resources Information Center

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.; Korzus, Edward

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required…

Ventromedial prefrontal cortex is obligatory for consolidation and reconsolidation of object recognition memory.

PubMed

Akirav, Irit; Maroun, Mouna

2006-12-01

Once consolidated, a long-term memory item could regain susceptibility to consolidation blockers, that is, reconsolidate, upon its reactivation. Both consolidation and reconsolidation require protein synthesis, but it is not yet known how similar these processes are in terms of molecular, cellular, and neural circuit mechanisms. Whereas most previous studies focused on aversive conditioning in the amygdala and the hippocampus, here we examine the role of the ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of object recognition memory. Object recognition memory is the ability to discriminate the familiarity of previously encountered objects. We found that microinfusion of the protein synthesis inhibitor anisomycin or the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) into the vmPFC, immediately after training, resulted in impairment of long-term (24 h) but not short-term (3 h) recognition memory. Similarly, microinfusion of anisomycin or APV into the vmPFC immediately after reactivation of the long-term memory impaired recognition memory 24 h, but not 3 h, post-reactivation. These results indicate that both protein synthesis and NMDA receptors are required for consolidation and reconsolidation of recognition memory in the vmPFC.

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

PubMed Central

Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian; Zhang, Min; Li, Wanhe; Zhong, Yi

2015-01-01

Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β′1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts. PMID:26627257

Working memory load reduces the late positive potential and this effect is attenuated with increasing anxiety.

PubMed

MacNamara, Annmarie; Ferri, Jamie; Hajcak, Greg

2011-09-01

Emotion regulation decreases the processing of arousing stimuli, as indexed by the late positive potential (LPP), an electrocortical component that varies in amplitude with emotional arousal. Emotion regulation increases activity in the prefrontal areas associated with cognitive control, including the dosolateral prefrontal cortex (DLPFC). The present study manipulated working memory load, known to activate the DLPFC, and recorded the LPP elicited by aversive and neutral IAPS pictures presented during the retention interval. The LPP was larger on low-load compared to high-load trials, and on trials with aversive compared to neutral pictures. These LPP data suggest that emotional content and working memory load have opposing effects on attention to distracting stimuli. State anxiety was associated with reduced modulation of the LPP by working memory load. Results are discussed in terms of competition for attention between emotion and cognition and suggest a relationship between DLPFC activation and the allocation of attentional resources to distracting visual stimuli-a relationship that may be disrupted with increasing anxiety.

Evaluation of color preference in zebrafish for learning and memory.

PubMed

Avdesh, Avdesh; Martin-Iverson, Mathew T; Mondal, Alinda; Chen, Mengqi; Askraba, Sreten; Morgan, Newman; Lardelli, Michael; Groth, David M; Verdile, Giuseppe; Martins, Ralph N

2012-01-01

There is growing interest in using zebrafish (Danio rerio) as a model of neurodegenerative disorders such as Alzheimer's disease. A zebrafish model of tauopathies has recently been developed and characterized in terms of presence of the pathological hallmarks (i.e., neurofibrillary tangles and cell death). However, it is also necessary to validate these models for function by assessing learning and memory. The majority of tools to assess memory and learning in animal models involve visual stimuli, including color preference. The color preference of zebrafish has received little attention. To validate zebrafish as a model for color-associated-learning and memory, it is necessary to evaluate its natural preferences or any pre-existing biases towards specific colors. In the present study, we have used four different colors (red, yellow, green, and blue) to test natural color preferences of the zebrafish using two procedures: Place preference and T-maze. Results from both experiments indicate a strong aversion toward blue color relative to all other colors (red, yellow, and green) when tested in combinations. No preferences or biases were found among reds, yellows, and greens in the place preference procedure. However, red and green were equally preferred and both were preferred over yellow by zebrafish in the T-maze procedure. The results from the present study show a strong aversion towards blue color compared to red, green, and yellow, with yellow being less preferred relative to red and green. The findings from this study may underpin any further designing of color-based learning and memory paradigms or experiments involving aversion, anxiety, or fear in the zebrafish.

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

PubMed

Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation.

PubMed

Ratano, Patrizia; Petrella, Carla; Forti, Fabrizio; Passeri, Pamela Petrocchi; Morena, Maria; Palmery, Maura; Trezza, Viviana; Severini, Cinzia; Campolongo, Patrizia

2018-05-26

The endocannabinoid system is a key modulator of memory consolidation for aversive experiences. We recently found that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its hydrolysis, facilitates memory consolidation through a concurrent activation of both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the role played on memory consolidation by the other major endocannabinoid, 2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic administration of the MAGL inhibitor JZL184 to rats immediately after training of the inhibitory avoidance task. Pharmacological enhancement of 2-AG tone facilitated memory consolidation through activation of CB2 receptor signaling. Moreover, we found that increased 2-AG signaling prevented the activation of the mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus through a CB2-dependent mechanism. Our results identify a fundamental role for 2-AG and CB2 receptors in the modulation of memory consolidation for aversive experiences. Copyright © 2018 Elsevier Ltd. All rights reserved.

Emotional reactivity and cognitive performance in aversively motivated tasks: a comparison between four rat strains.

PubMed

van der Staay, F Josef; Schuurman, Teun; van Reenen, Cornelis G; Korte, S Mechiel

2009-12-15

Cognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity. The performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined. Strain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait. Our findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing.

Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.

PubMed

Stinus, Luis; Cador, Martine; Zorrilla, Eric P; Koob, George F

2005-01-01

Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 microg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF1) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.

21 CFR 882.5235 - Aversive conditioning device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Aversive conditioning device. 882.5235 Section 882.5235 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5235 Aversive conditioning...

21 CFR 882.5235 - Aversive conditioning device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Aversive conditioning device. 882.5235 Section 882.5235 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5235 Aversive conditioning...

Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion

PubMed Central

Mickley, G. Andrew; Hoxha, Nita; Luchsinger, Joseph L.; Rogers, Morgan M.; Wiles, Nathanael R.

2013-01-01

Elevation of brain magnesium enhances synaptic plasticity and extinction of conditioned fear memories. This experiment examined the generalizability of this phenomenon by studying the effects of a novel magnesium compound, magnesium-L-threonate (MgT), on conditioned taste aversion (CTA) extinction and spontaneous recovery (SR). Adult male Sprague-Dawley rats were maintained on a 23-hour water deprivation cycle and acquired a CTA following the taste of a CS [0.3% saccharin + 16mg/ml MgT (SAC+MgT)] paired with a US [81 mg/kg (i.p.) Lithium Chloride (LiCl)]. Following CTA acquisition, rats drank a water + MgT solution for up to 1 hour/day over the next 31 days. For 14 additional days, some animals continued water + MgT treatment, but others drank water only to allow MgT to be eliminated from the body. We then employed 2 different extinction paradigms: (1) CS-Only (CSO), in which SAC was presented, every-other day, or (2) Explicitly Unpaired (EU), in which both SAC and LiCl were presented, but on alternate days. EU extinction procedures have been shown to speed CTA extinction and reduce spontaneous recovery of the aversion. Throughout extinction, half of the rats in each group continued to drink MgT (now in SAC or supplemental water+MgT solution), whereas the other half drank SAC only/water only until SAC drinking reached ≥ 90% of baseline (asymptotic extinction). Rats receiving MgT just before/during extinction drank less SAC on the first day of extinction suggesting that they had retained a stronger CTA. MgT enhanced the rate of extinction. Furthermore, the MgT-treated rats showed a relatively modest SR of the CTA 30 days later – indicating that the extinction procedure was more effective for these animals. Our data suggest that long-term dietary MgT may enhance the consolidation/retention of a CTA, speed extinction, and inhibit SR of this learned aversion. PMID:23474371

Lesion of the rostromedial tegmental nucleus increases voluntary ethanol consumption and accelerates extinction of ethanol-induced conditioned taste aversion.

PubMed

Sheth, Chandni; Furlong, Teri M; Keefe, Kristen A; Taha, Sharif A

2016-10-01

Ethanol has rewarding and aversive properties, and the balance of these properties influences voluntary ethanol consumption. Preclinical and clinical evidence show that the aversive properties of ethanol limit intake. The neural circuits underlying ethanol-induced aversion learning are not fully understood. We have previously shown that the lateral habenula (LHb), a region critical for aversive conditioning, plays an important role in ethanol-directed behaviors. However, the neurocircuitry through which LHb exerts its actions is unknown. In the present study, we investigate a role for the rostromedial tegmental nucleus (RMTg), a major LHb projection target, in regulating ethanol-directed behaviors. Rats received either sham or RMTg lesions and were studied during voluntary ethanol consumption; operant ethanol self-administration, extinction, and yohimbine-induced reinstatement of ethanol-seeking; and ethanol-induced conditioned taste aversion (CTA). RMTg lesions increased voluntary ethanol consumption and accelerated extinction of ethanol-induced CTA. The RMTg plays an important role in regulating voluntary ethanol consumption, possibly by mediating ethanol-induced aversive conditioning.

Imprinting: When Early Life Memories Make Food Smell Bad.

PubMed

Rayes, Diego; Alkema, Mark J

2016-05-09

A recent study has found that pathogen exposure early in the life of the nematode Caenorhabditis elegans leads to a long-lasting aversion that requires distinct sets of neurons for the formation and retrieval of the imprinted memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dopamine and extinction: A convergence of theory with fear and reward circuitry

PubMed Central

Abraham, Antony D.; Neve, Kim A.; Lattal, K. Matthew

2014-01-01

Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine’s function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. PMID:24269353

Dopamine and extinction: a convergence of theory with fear and reward circuitry.

PubMed

Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

2014-02-01

Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits.

PubMed

Rossignoli, Matheus Teixeira; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Do Val da Silva, Raquel Araujo; Bueno-Junior, Lezio Soares; Kandratavicius, Ludmyla; Peixoto-Santos, José Eduardo; Crippa, José Alexandre; Cecilio Hallak, Jaime Eduardo; Zuardi, Antonio Waldo; Szawka, Raphael Escorsim; Anselmo-Franci, Janete; Leite, João Pereira; Romcy-Pereira, Rodrigo Neves

2017-05-14

The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Parvalbumin interneurons constrain the size of the lateral amygdala engram.

PubMed

Morrison, Dano J; Rashid, Asim J; Yiu, Adelaide P; Yan, Chen; Frankland, Paul W; Josselyn, Sheena A

2016-11-01

Memories are thought to be represented by discrete physiological changes in the brain, collectively referred to as an engram, that allow patterns of activity present during learning to be reactivated in the future. During the formation of a conditioned fear memory, a subset of principal (excitatory) neurons in the lateral amygdala (LA) are allocated to a neuronal ensemble that encodes an association between an initially neutral stimulus and a threatening aversive stimulus. Previous experimental and computational work suggests that this subset consists of only a small proportion of all LA neurons, and that this proportion remains constant across different memories. Here we examine the mechanisms that contribute to the stability of the size of the LA component of an engram supporting a fear memory. Visualizing expression of the activity-dependent gene Arc following memory retrieval to identify neurons allocated to an engram, we first show that the overall size of the LA engram remains constant across conditions of different memory strength. That is, the strength of a memory was not correlated with the number of LA neurons allocated to the engram supporting that memory. We then examine potential mechanisms constraining the size of the LA engram by expressing inhibitory DREADDS (designer receptors exclusively activated by designer drugs) in parvalbumin-positive (PV + ) interneurons of the amygdala. We find that silencing PV + neurons during conditioning increases the size of the engram, especially in the dorsal subnucleus of the LA. These results confirm predictions from modeling studies regarding the role of inhibition in shaping the size of neuronal memory ensembles and provide additional support for the idea that neurons in the LA are sparsely allocated to the engram based on relative neuronal excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

The touchscreen operant platform for testing learning and memory in rats and mice

PubMed Central

Horner, Alexa E.; Heath, Christopher J.; Hvoslef-Eide, Martha; Kent, Brianne A.; Kim, Chi Hun; Nilsson, Simon R. O.; Alsiö, Johan; Oomen, Charlotte A.; Holmes, Andrew; Saksida, Lisa M.; Bussey, Timothy J.

2014-01-01

Summary An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive, rather than aversive reinforcement), has high translational potential, and lends itself to a high degree of standardisation and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer’s disease, schizophrenia, Huntington’s disease, frontotemporal dementia), and characterisation of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: Visual Discrimination, Object-Location Paired-Associates Learning, Visuomotor Conditional Learning and Autoshaping. It is accompanied by two further protocols using the touchscreen platform to assess executive function, working memory and pattern separation. PMID:24051959

Disrupting reconsolidation of fear memory in humans by a noradrenergic β-blocker.

PubMed

Kindt, Merel; Soeter, Marieke; Sevenster, Dieuwke

2014-12-18

The basic design used in our human fear-conditioning studies on disrupting reconsolidation includes testing over different phases across three consecutive days. On day 1 - the fear acquisition phase, healthy participants are exposed to a series of picture presentations. One picture stimulus (CS1+) is repeatedly paired with an aversive electric stimulus (US), resulting in the acquisition of a fear association, whereas another picture stimulus (CS2-) is never followed by an US. On day 2 - the memory reactivation phase, the participants are re-exposed to the conditioned stimulus without the US (CS1-), which typically triggers a conditioned fear response. After the memory reactivation we administer an oral dose of 40 mg of propranolol HCl, a β-adrenergic receptor antagonist that indirectly targets the protein synthesis required for reconsolidation by inhibiting the noradrenaline-stimulated CREB phosphorylation. On day 3 - the test phase, the participants are again exposed to the unreinforced conditioned stimuli (CS1- and CS2-) in order to measure the fear-reducing effect of the manipulation. This retention test is followed by an extinction procedure and the presentation of situational triggers to test for the return of fear. Potentiation of the eye blink startle reflex is measured as an index for conditioned fear responding. Declarative knowledge of the fear association is measured through online US expectancy ratings during each CS presentation. In contrast to extinction learning, disrupting reconsolidation targets the original fear memory thereby preventing the return of fear. Although the clinical applications are still in their infancy, disrupting reconsolidation of fear memory seems to be a promising new technique with the prospect to persistently dampen the expression of fear memory in patients suffering from anxiety disorders and other psychiatric disorders.

Glia protein aquaporin-4 regulates aversive motivation of spatial memory in Morris water maze.

PubMed

Zhang, Ji; Li, Ying; Chen, Zhong-Guo; Dang, Hui; Ding, Jian-Hua; Fan, Yi; Hu, Gang

2013-12-01

Although extensive investigation has revealed that an astrocyte-specific protein aquaporin-4 (AQP4) participates in regulating synaptic plasticity and memory, a functional relationship between AQP4 and learning processing has not been clearly established. This study was designed to test our hypothesis that AQP4 modulates the aversive motivation in Morris water maze (MWM). Using hidden platform training, we observed that AQP4 KO mice significantly decreased their swimming velocity compared with wild-type (WT) mice. To test for a relationship between velocities and escape motivation, we removed the platform and subjected a new group of mice similar to the session of hidden platform training. We found that KO mice exhibited a gradual reduction in swimming velocity, while WT mice did not alter their velocity. In the subsequent probe trial, KO mice after no platform training significantly decreased their mean velocity compared with those KO mice after hide platform training. However, all of KO mice were not impaired in their ability to locate a visible, cued escape platform. Our findings, along with a previous report that AQP4 regulates memory consolidation, implicate a novel role for this glial protein in modulating the aversive motivation in spatial learning paradigm. © 2013 John Wiley & Sons Ltd.

Prefrontal consolidation supports the attainment of fear memory accuracy.

PubMed

Vieira, Philip A; Lovelace, Jonathan W; Corches, Alex; Rashid, Asim J; Josselyn, Sheena A; Korzus, Edward

2014-08-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. © 2014 Vieira et al.; Published by Cold Spring Harbor Laboratory Press.

Effects of Swim Stress on Neophobia and Reconditioning Using a Conditioned Taste Aversion Procedure

ERIC Educational Resources Information Center

Walker, Jennifer M.; Ramsey, Ashley K.; Fowler, Stephanie W.; Schachtman, Todd R.

2012-01-01

Previous research has found that swim stress during a classical conditioning trial attenuates conditioned taste aversion (CTA). In the current study, rats were used to examine the effects of inescapable swim stress on the habituation of neophobia to a flavored solution and reacquisition of an extinguished conditioned taste aversion. In Experiment…

Differential regulation of glutamic acid decarboxylase gene expression after extinction of a recent memory vs. intermediate memory.

PubMed

Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jörg; Pape, Hans-Christian

2012-04-17

Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65 isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). However, a detailed analysis of changes in gene expression of GAD in the subregions comprising the extinction network has not been undertaken. Here, we report changes in gene expression of the GAD65 and GAD67 isoforms of GAD, as measured by relative quantitative real-time RT-PCR, in subregions of the amygdala, hippocampus, and prefrontal cortex 24-26 h after extinction of a recent (1-d) or intermediate (14-d) fear memory. Our results show that extinction of a recent memory induces a down-regulation of Gad65 gene expression in the hippocampus (CA1, dentate gyrus) and an up-regulation of Gad67 gene expression in the infralimbic cortex. Extinguishing an intermediate memory increased Gad65 gene expression in the central amygdala. These results indicate a differential regulation of Gad gene expression after extinction of a recent memory vs. intermediate memory.

Modulation of Gene Expression in Contextual Fear Conditioning in the Rat

PubMed Central

Macchi, Monica; Ciampini, Cristina; Bernardi, Rodolfo; Baldi, Elisabetta; Bucherelli, Corrado; Brunelli, Marcello; Scuri, Rossana

2013-01-01

In contextual fear conditioning (CFC) a single training leads to long-term memory of context-aversive electrical foot-shocks association. Mid-temporal regions of the brain of trained and naive rats were obtained 2 days after conditioning and screened by two-directional suppression subtractive hybridization. A pool of differentially expressed genes was identified and some of them were randomly selected and confirmed with qRT-PCR assay. These transcripts showed high homology for rat gene sequences coding for proteins involved in different cellular processes. The expression of the selected transcripts was also tested in rats which had freely explored the experimental apparatus (exploration) and in rats to which the same number of aversive shocks had been administered in the same apparatus, but temporally compressed so as to make the association between painful stimuli and the apparatus difficult (shock-only). Some genes resulted differentially expressed only in the rats subjected to CFC, others only in exploration or shock-only rats, whereas the gene coding for translocase of outer mitochondrial membrane 20 protein and nardilysin were differentially expressed in both CFC and exploration rats. For example, the expression of stathmin 1 whose transcripts resulted up regulated was also tested to evaluate the transduction and protein localization after conditioning. PMID:24278235

Fractionation of Spatial Memory in GRM2/3 (mGlu2/mGlu3) Double Knockout Mice Reveals a Role for Group II Metabotropic Glutamate Receptors at the Interface Between Arousal and Cognition

PubMed Central

Lyon, Louisa; Burnet, Philip WJ; Kew, James NC; Corti, Corrado; Rawlins, J Nicholas P; Lane, Tracy; De Filippis, Bianca; Harrison, Paul J; Bannerman, David M

2011-01-01

Group II metabotropic glutamate receptors (mGluR2 and mGluR3, encoded by GRM2 and GRM3) are implicated in hippocampal function and cognition, and in the pathophysiology and treatment of schizophrenia and other psychiatric disorders. However, pharmacological and behavioral studies with group II mGluR agonists and antagonists have produced complex results. Here, we studied hippocampus-dependent memory in GRM2/3 double knockout (GRM2/3−/−) mice in an iterative sequence of experiments. We found that they were impaired on appetitively motivated spatial reference and working memory tasks, and on a spatial novelty preference task that relies on animals' exploratory drive, but were unimpaired on aversively motivated spatial memory paradigms. GRM2/3−/− mice also performed normally on an appetitively motivated, non-spatial, visual discrimination task. These results likely reflect an interaction between GRM2/3 genotype and the arousal-inducing properties of the experimental paradigm. The deficit seen on appetitive and exploratory spatial memory tasks may be absent in aversive tasks because the latter induce higher levels of arousal, which rescue spatial learning. Consistent with an altered arousal–cognition relationship in GRM2/3−/− mice, injection stress worsened appetitively motivated, spatial working memory in wild-types, but enhanced performance in GRM2/3−/− mice. GRM2/3−/− mice were also hypoactive in response to amphetamine. This fractionation of hippocampus-dependent memory depending on the appetitive-aversive context is to our knowledge unique, and suggests a role for group II mGluRs at the interface of arousal and cognition. These arousal-dependent effects may explain apparently conflicting data from previous studies, and have translational relevance for the involvement of these receptors in schizophrenia and other disorders. PMID:21832989

Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

PubMed Central

Gilmartin, Marieke R.; Helmstetter, Fred J.

2010-01-01

The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increased activity during the trace interval separating the CS and UCS. We investigated the contribution of prefrontal neural activity in the rat to the acquisition of trace fear conditioning using microinfusions of the γ-aminobutyric acid type A (GABAA) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-d-aspartate (NMDA) receptor-mediated signaling in trace fear conditioning using the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Temporary inactivation of prefrontal activity with muscimol or blockade of NMDA receptor-dependent transmission in mPFC impaired the acquisition of trace, but not delay, conditional fear responses. Simultaneously acquired contextual fear responses were also impaired in drug-treated rats exposed to trace or delay, but not unpaired, training protocols. Our results support the idea that synaptic plasticity within the mPFC is critical for the long-term storage of memory in trace fear conditioning. PMID:20504949

Perirhinal Cortex Muscarinic Receptor Blockade Impairs Taste Recognition Memory Formation

ERIC Educational Resources Information Center

Gutierrez, Ranier; De la Cruz, Vanesa; Rodriguez-Ortiz, Carlos J.; Bermudez-Rattoni, Federico

2004-01-01

The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition…

Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats.

PubMed

Lin, Jue; Liu, Lingqi; Wen, Quan; Zheng, Chunming; Gao, Yang; Peng, Shuxian; Tan, Yalun; Li, Yanqin

2014-01-01

The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.

Fear of losing money? Aversive conditioning with secondary reinforcers.

PubMed

Delgado, M R; Labouliere, C D; Phelps, E A

2006-12-01

Money is a secondary reinforcer that acquires its value through social communication and interaction. In everyday human behavior and laboratory studies, money has been shown to influence appetitive or reward learning. It is unclear, however, if money has a similar impact on aversive learning. The goal of this study was to investigate the efficacy of money in aversive learning, comparing it with primary reinforcers that are traditionally used in fear conditioning paradigms. A series of experiments were conducted in which participants initially played a gambling game that led to a monetary gain. They were then presented with an aversive conditioning paradigm, with either shock (primary reinforcer) or loss of money (secondary reinforcer) as the unconditioned stimulus. Skin conductance responses and subjective ratings indicated that potential monetary loss modulated the conditioned response. Depending on the presentation context, the secondary reinforcer was as effective as the primary reinforcer during aversive conditioning. These results suggest that stimuli that acquire reinforcing properties through social communication and interaction, such as money, can effectively influence aversive learning.

Differentiating aversive conditioning in bistable perception: Avoidance of a percept vs. salience of a stimulus.

PubMed

Wilbertz, Gregor; Sterzer, Philipp

2018-05-01

Alternating conscious visual perception of bistable stimuli is influenced by several factors. In order to understand the effect of negative valence, we tested the effect of two types of aversive conditioning on dominance durations in binocular rivalry. Participants received either aversive classical conditioning of the stimuli shown alone between rivalry blocks, or aversive percept conditioning of one of the two possible perceptual choices during rivalry. Both groups showed successful aversive conditioning according to skin conductance responses and affective valence ratings. However, while classical conditioning led to an immediate but short-lived increase in dominance durations of the conditioned stimulus, percept conditioning yielded no significant immediate effect but tended to decrease durations of the conditioned percept during extinction. These results show dissociable effects of value learning on perceptual inference in situations of perceptual conflict, depending on whether learning relates to the decision between conflicting perceptual choices or the sensory stimuli per se. Copyright © 2018 Elsevier Inc. All rights reserved.

Conditioned food aversion for control of poisoning by Ipomoea carnea subsp. fistulosa

USDA-ARS?s Scientific Manuscript database

Conditioned food aversion is a technique that can be used to train livestock to avoid ingestion of poisonous plants. This study tested the efficacy and durability of conditioned food aversion to eliminate goat’s consumption of Ipomoea carnea subsp. fistulosa. We used 14 young Moxotó goats, which wer...

Failure of Serial Taste-Taste Compound Presentations to Produce Overshadowing of Extinction of Conditioned Taste Aversion

ERIC Educational Resources Information Center

Pineno, Oskar

2010-01-01

Two experiments were conducted to study overshadowing of extinction in a conditioned taste aversion preparation. In both experiments, aversive conditioning with sucrose was followed by extinction treatment with either sucrose alone or in compound with another taste, citric acid. Experiment 1 employed a simultaneous compound extinction treatment…

A Fully Automated Drosophila Olfactory Classical Conditioning and Testing System for Behavioral Learning and Memory Assessment

PubMed Central

Jiang, Hui; Hanna, Eriny; Gatto, Cheryl L.; Page, Terry L.; Bhuva, Bharat; Broadie, Kendal

2016-01-01

Background Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory analyses for high-throughput pharmacological and genetic studies. New Method The automated system employs a linear actuator coupled to an odorant T-maze with airflow-mediated transfer of animals between training and testing stages. Odorant, airflow and electrical shock delivery are automatically administered and monitored during training trials. Control software allows operator-input variables to define parameters of Drosophila learning, short-term memory and long-term memory assays. Results The approach allows accurate learning/memory determinations with operational fail-safes. Automated learning indices (immediately post-training) and memory indices (after 24 hours) are comparable to traditional manual experiments, while minimizing experimenter involvement. Comparison with Existing Methods The automated system provides vast improvements over labor-intensive manual approaches with no experimenter involvement required during either training or testing phases. It provides quality control tracking of airflow rates, odorant delivery and electrical shock treatments, and an expanded platform for high-throughput studies of combinational drug tests and genetic screens. The design uses inexpensive hardware and software for a total cost of ~$500US, making it affordable to a wide range of investigators. Conclusions This study demonstrates the design, construction and testing of a fully automated Drosophila olfactory classical association apparatus to provide low-labor, high-fidelity, quality-monitored, high-throughput and inexpensive learning and memory behavioral assays. PMID:26703418

A fully automated Drosophila olfactory classical conditioning and testing system for behavioral learning and memory assessment.

PubMed

Jiang, Hui; Hanna, Eriny; Gatto, Cheryl L; Page, Terry L; Bhuva, Bharat; Broadie, Kendal

2016-03-01

Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory analyses for high-throughput pharmacological and genetic studies. The automated system employs a linear actuator coupled to an odorant T-maze with airflow-mediated transfer of animals between training and testing stages. Odorant, airflow and electrical shock delivery are automatically administered and monitored during training trials. Control software allows operator-input variables to define parameters of Drosophila learning, short-term memory and long-term memory assays. The approach allows accurate learning/memory determinations with operational fail-safes. Automated learning indices (immediately post-training) and memory indices (after 24h) are comparable to traditional manual experiments, while minimizing experimenter involvement. The automated system provides vast improvements over labor-intensive manual approaches with no experimenter involvement required during either training or testing phases. It provides quality control tracking of airflow rates, odorant delivery and electrical shock treatments, and an expanded platform for high-throughput studies of combinational drug tests and genetic screens. The design uses inexpensive hardware and software for a total cost of ∼$500US, making it affordable to a wide range of investigators. This study demonstrates the design, construction and testing of a fully automated Drosophila olfactory classical association apparatus to provide low-labor, high-fidelity, quality-monitored, high-throughput and inexpensive learning and memory behavioral assays. Copyright © 2015 Elsevier B.V. All rights reserved.

Rescripting Memory, Redefining the Self: A Meta-Emotional Perspective on the Hypothesized Mechanism(s) of Imagery Rescripting.

PubMed

Mancini, Alessandra; Mancini, Francesco

2018-01-01

Imagery Rescripting (ImRs) is a therapeutic technique that aims to reduce the distress associated with negative memories of early aversive experiences. It consists of prompting patients to rescript the autobiographical memory in line with their unmet needs. In recent years, ImRs was found effective in reducing symptoms of disorders such as depression, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, and personality disorders. However, the cognitive mechanisms underlying such broad effectiveness are currently an object of debate. Empirical evidence has shown that ImRs reduces the negative self-belief derived from aversive memories in different types of mental disorders. However, existing accounts are not very accurate in explaining how this change in self-belief occurs and therefore why ImRs is effective across psychopathologies. We propose that ImRs changes the semantic self-representation encapsulated in the aversive memory by reducing the meta-emotional problem (i.e., perceiving a negative emotion as problematic and unacceptable). Empirical evidence implicates the meta-emotional problem or "secondary problem" in the maintenance of different disorders and has shown that treating it leads to symptoms reduction. Here we hypothesize that: (i) ImRs as a stand-alone treatment may lead to a reduction of symptoms; negative self-belief and the meta-emotional problem; and (ii) the reduction of the meta-emotional problem might mediate the relation between symptoms and negative self-belief reduction. To test our hypothesis, we present an experimental procedure that could be used in future studies. We conclude discussing the existing theoretical frameworks that attempt to unravel the mechanisms that play a role in ImRs.

Training memory without aversion: Appetitive hole-board spatial learning increases adult hippocampal neurogenesis.

PubMed

Sampedro-Piquero, Patricia; Moreno-Fernández, Román D; Carmen Mañas-Padilla, M; Gil-Rodríguez, Sara; Gavito, Ana Luisa; Pavón, Francisco J; Pedraza, Carmen; García-Fernández, María; Ladrón de Guevara-Miranda, David; Santín, Luis J; Castilla-Ortega, Estela

2018-05-01

Learning experiences are potent modulators of adult hippocampal neurogenesis (AHN). However, the vast majority of findings on the learning-induced regulation of AHN derive from aversively-motivated tasks, mainly the water maze paradigm, in which stress is a confounding factor that affects the AHN outcome. Currently, little is known regarding the effect of appetitively-motivated training on AHN. Hence we studied how spatial learning to find food rewards in a hole-board maze modulates AHN (cell proliferation and immature neurons) and AHN-related hippocampal neuroplasticity markers (BDNF, IGF-II and CREB phosphorylation) in mice. The 'Trained' mice were tested for both spatial reference and working memory and compared to 'Pseudotrained' mice (exposed to different baited holes in each session, thus avoiding the reference memory component of the task) and 'Control' mice (exposed to the maze without rewards). In contrast to Pseudotrained and Control mice, the number of proliferating hippocampal cells were reduced in Trained mice, but they notably increased their population of immature neurons assessed by immunohistochemistry. This evidence shows that hole-board spatial reference learning diminishes cell proliferation in favor of enhancing young neurons' survival. Interestingly, the enhanced AHN in the Trained mice (specifically in the suprapyramidal blade) positively correlated with their reference memory performance, but not with their working memory. Furthermore, the Trained animals increased the hippocampal protein expression of all the neuroplasticity markers analyzed by western blot. Results show that the appetitively-motivated hole-board task is a useful paradigm to potentiate and/or investigate AHN and hippocampal plasticity minimizing aversive variables such as fear or stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Examinations of the reward comparison hypothesis: The modulation of gender and footshock.

PubMed

Huang, Andrew Chih Wei; Wang, Cheng Chung; Wang, Shiun

2015-11-01

The reward comparison hypothesis suggests that drugs of abuse-induced conditioned saccharin suppression intake is due to the reward value of drugs of abuse that outweighs that of a saccharin solution dissociating from the aversive LiCl-induced conditioned taste aversion (CTA). Huang and Hsiao (2008) provided some conflict data to challenge the reward comparison hypothesis. Whether the rewarding drugs of abuse-induced conditioned suppression and the aversive LiCl-induced CTA resulted from aversion or reward should be addressed. The present study investigated how gender and footshock affect aversive LiCl- and rewarding morphine- and methamphetamine (MAMPH)-induced conditioned suppression to re-examine the reward comparison hypothesis. The results indicated that gender and footshock did not directly influence the aversive LiCl-induced CTA or rewarding morphine- and MAMPH-induced conditioned suppression. The gender effect interacted with the drug effect in the aversive LiCl- and rewarding MAMPH-induced conditioned suppression but did not interact with the drug effect in the rewarding morphine-induced conditioned suppression. Footshock interacted with the drug effect in rewarding morphine- and MAMPH-induced conditioned suppression, but footshock did not interact with the drug effect in the aversive LiCl-induced CTA. Therefore, the gender and footshock effects might play a modulatory (but not a mediating) role with the drug effect. The present data indicated that footshock modulates drugs of abuse-induced conditioned suppression, which is consistent with the reward comparison hypothesis, but our findings with regard to the modulatory role of the gender effect and the drug effect do not support this hypothesis. The reward comparison hypothesis should be discussed and possibly reconsidered. Copyright © 2015. Published by Elsevier Inc.

Immunotoxic cholinergic lesions in the basal forebrain reverse the effects of entorhinal cortex lesions on conditioned odor aversion in the rat.

PubMed

Ferry, Barbara; Herbeaux, Karin; Cosquer, Brigitte; Traissard, Natalia; Galani, Rodrigue; Cassel, Jean-Christophe

2007-07-01

Conditioned odor aversion (COA) corresponds to the avoidance of an odorized-tasteless solution (conditioned stimulus, CS) previously paired with toxicosis. COA occurs only when the interstimulus interval (ISI) is kept short, suggesting that the memory trace of the odor is subject to rapid decay. Previous experiments have shown that the entorhinal cortex (EC) is involved in the acquisition of COA, since lesion of the EC rendered COA tolerant to long ISI. Because EC lesions induce a septo-hippocampal cholinergic sprouting, the present experiment investigated whether COA tolerance to long ISI may be linked to this sprouting reaction. In a first experiment, male Long-Evans rats subjected to bilateral excitotoxic EC lesions combined to intracerebroventricular infusions of the selective cholinergic immunotoxin 192 IgG-saporin were exposed to odor-toxicosis pairing using a long ISI (120 min). Results showed that EC-lesioned rats displayed COA with the long ISI but not the control groups. In rats with EC combined to 192 IgG-saporin lesions, histological analysis demonstrated no evidence for cholinergic septo-hippocampal sprouting. In a second experiment, animals with 192-IgG saporin lesion showed a marked COA with a short ISI (5 min). These results suggest that the COA with the long ISI found in rats with EC lesions might involve a functional activity related to the EC lesion-induced hippocampal cholinergic sprouting. As the injection of 192 IgG-saporin alone did not affect COA with a short ISI, our data also point to a possible role of hippocampal cholinergic neurons in the modulation of memory processes underlying COA.

Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion.

PubMed

Kim, Kyu-Nam; Kim, Bom-Taeck; Kim, Young-Sang; Lee, Jong-Ho; Jahng, Jeong Won

2014-05-05

Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA. Copyright © 2014 Elsevier B.V. All rights reserved.

Fear memory for cue and context: opposite and time-dependent effects of a physiological dose of corticosterone in male BALB/c and C57BL/6J mice.

PubMed

Diamantopoulou, Anastasia; Oitzl, Melly S; Grauer, Ettie

2012-07-23

Highly emotional, stress reactive BALB/c mice secrete more corticosterone in response to fear conditioning than the low stress reactive C57BL/6J mice. Fear memory to cue and context differs between the strains. We injected corticosterone at physiological concentrations (250 μg/kg i.p.) 30 min before fear conditioning. Fear memory was tested 48 and 72 h later. Although corticosterone had little effect on acquisition, it differentially affected fear memories in strain dependent manner: while BALB/c mice decreased freezing during cue and context episodes, C57BL/6J mice showed an overall increase in freezing. BALB/c mice showed extinction over days while no such extinction was seen in C57BL/6J mice. Evaluation of these data in the perspective of previous studies using the same fear conditioning paradigm with corticosterone injections 5 min before or immediately after acquisition, revealed the impact of corticosterone during conditioning on the strength of fear memories. In C57BL/6J mice the overall increase in fear memories was higher if corticosterone was injected 30 min pre acquisition than if injected 5 min pre. In contrast, BALB/c mice showed reduced fear memories when injected 30 min pre compared to that seen 5 min pre acquisition. Both strains showed decreased fear memories compared to vehicle if corticosterone was administered immediately after acquisition. We conclude that the timing of physiologically relevant, stress levels increase in corticosterone is essential for the processing of aversive events and the formation of fear memories. However, the quality of the effect depends on the genetic background. These findings contribute to the understanding of the etiology of stress-related disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Emotional reactivity and cognitive performance in aversively motivated tasks: a comparison between four rat strains

PubMed Central

2009-01-01

Background Cognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity. Methods The performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined. Results Strain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait. Conclusions Our findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing. PMID:20003525

Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Risinger, F.O.; Cunningham, C.L.

1992-01-01

Genetic differences in the hyperglycemic response to acute ethanol exposure and ethanol-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J and DBA/2J mice were injected with ethanol and blood glucose levels determined over 4 h. C57 mice demonstrated greater dose-dependent elevations in blood glucose compared to DBA mice. In a conditioned taste aversion procedure, water deprived mice received ethanol injections immediately after access to a NaCl flavored solution. DBA mice developed aversion to the ethanol-paired flavor at a lower dose than C57 mice. These results provide further support for a possible inverse genetic relationship between sensitivity tomore » ethanol-induced hyperglycemia and sensitivity to conditioned taste aversion.« less

Preexposure to Salty and Sour Taste Enhances Conditioned Taste Aversion to Novel Sucrose

ERIC Educational Resources Information Center

Flores, Veronica L.; Moran, Anan; Bernstein, Max; Katz, Donald B.

2016-01-01

Conditioned taste aversion (CTA) is an intensively studied single-trial learning paradigm whereby animals are trained to avoid a taste that has been paired with malaise. Many factors influence the strength of aversion learning; prominently studied among these is taste novelty--the fact that preexposure to the taste conditioned stimulus (CS)…

Recalling an Aversive Experience by Day-Old Chicks Is Not Dependent on Somatic Protein Synthesis

ERIC Educational Resources Information Center

Mileusnic, Radmila; Lancashire, Christine L.; Rose, Steven P. R.

2005-01-01

Long-term memory is dependent on protein synthesis and inhibiting such synthesis following training results in amnesia for the task. Proteins synthesized during training must be transported to the synapse and disrupting microtubules with Colchicines, and hence, blocking transport, results in transient amnesia. Reactivating memory for a previously…

Effects of 5-HT and insulin on learning and memory formation in food-deprived snails.

PubMed

Aonuma, Hitoshi; Totani, Yuki; Kaneda, Mugiho; Nakamura, Ryota; Watanabe, Takayuki; Hatakeyama, Dai; Dyakonova, Varvara E; Lukowiak, Ken; Ito, Etsuro

2018-02-01

The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). How well they learn and form memory depends on the degree of food deprivation. Serotonin (5-HT) plays an important role in mediating feeding, and insulin enhances the memory consolidation process following CTA training. However, the relationship between these two signaling pathways has not been addressed. We measured the 5-HT content in the central nervous system (CNS) of snails subjected to different durations of food deprivation. One-day food-deprived snails, which exhibit the best learning and memory, had the lowest 5-HT content in the CNS, whereas 5-day food-deprived snails, which do not learn, had a high 5-HT content. Immersing 1-day food-deprived snails in 5-HT impaired learning and memory by causing an increase in 5-HT content, and that the injection of insulin into these snails reversed this impairment. We conclude that insulin rescues the CTA deficit and this may be due to a decrease in the 5-HT content in the CNS of Lymnaea. Copyright © 2018 Elsevier Inc. All rights reserved.

Recognition by Rats of Binary Taste Solutions and Their Components.

PubMed

Katagawa, Yoshihisa; Yasuo, Toshiaki; Suwabe, Takeshi; Yamamura, Tomoki; Gen, Keika; Sako, Noritaka

2016-09-13

This behavioral study investigated how rats conditioned to binary mixtures of preferred and aversive taste stimuli, respectively, responded to the individual components in a conditioned taste aversion (CTA) paradigm. The preference of stimuli was determined based on the initial results of 2 bottle preference test. The preferred stimuli included 5mM sodium saccharin (Sacc), 0.03M NaCl (Na), 0.1M Na, 5mM Sacc + 0.03M Na, and 5mM Sacc + 0.2mM quinine hydrochloride (Q), whereas the aversive stimuli tested were 1.0M Na, 0.2mM Q, 0.3mM Q, 5mM Sacc + 1.0M Na, and 5mM Sacc + 0.3mM Q. In CTA tests where LiCl was the unconditioned stimulus, the number of licks to the preferred binary mixtures and to all tested preferred components were significantly less than in control rats. No significant difference resulted between the number of licks to the aversive binary mixtures or to all tested aversive components. However, when rats pre-exposed to the aversive components contained of the aversive binary mixtures were conditioned to these mixtures, the number of licks to all the tested stimuli was significantly less than in controls. Rats conditioned to components of the aversive binary mixtures generalized to the binary mixtures containing those components. These results suggest that rats recognize and remember preferred and aversive taste mixtures as well as the preferred and aversive components of the binary mixtures, and that pre-exposure before CTA is an available method to study the recognition of aversive taste stimuli. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Generalization of Fear Inhibition by Disrupting Hippocampal Protein Synthesis-Dependent Reconsolidation Process

PubMed Central

Yang, Chih-Hao; Huang, Chiung-Chun; Hsu, Kuei-Sen

2011-01-01

Repetitive replay of fear memories may precipitate the occurrence of post-traumatic stress disorder and other anxiety disorders. Hence, the suppression of fear memory retrieval may help prevent and treat these disorders. The formation of fear memories is often linked to multiple environmental cues and these interconnected cues may act as reminders for the recall of traumatic experiences. However, as a convenience, a simple paradigm of one cue pairing with the aversive stimulus is usually used in studies of fear conditioning in animals. Here, we built a more complex fear conditioning model by presenting several environmental stimuli during fear conditioning and characterize the effectiveness of extinction training and the disruption of reconsolidation process on the expression of learned fear responses. We demonstrate that extinction training with a single-paired cue resulted in cue-specific attenuation of fear responses but responses to other cures were unchanged. The cue-specific nature of the extinction persisted despite training sessions combined with -cycloserine treatment reveals a significant weakness in extinction-based treatment. In contrast, the inhibition of the dorsal hippocampus (DH) but not the basolateral amygdala (BLA)-dependent memory reconsolidation process using either protein synthesis inhibitors or genetic disruption of cAMP-response-element-binding protein-mediated transcription comprehensively disrupted the learned connections between fear responses and all paired environmental cues. These findings emphasize the distinct role of the DH and the BLA in the reconsolidation process of fear memories and further indicate that the disruption of memory reconsolidation process in the DH may result in generalization of fear inhibition. PMID:21593730

Generalization of fear inhibition by disrupting hippocampal protein synthesis-dependent reconsolidation process.

PubMed

Yang, Chih-Hao; Huang, Chiung-Chun; Hsu, Kuei-Sen

2011-09-01

Repetitive replay of fear memories may precipitate the occurrence of post-traumatic stress disorder and other anxiety disorders. Hence, the suppression of fear memory retrieval may help prevent and treat these disorders. The formation of fear memories is often linked to multiple environmental cues and these interconnected cues may act as reminders for the recall of traumatic experiences. However, as a convenience, a simple paradigm of one cue pairing with the aversive stimulus is usually used in studies of fear conditioning in animals. Here, we built a more complex fear conditioning model by presenting several environmental stimuli during fear conditioning and characterize the effectiveness of extinction training and the disruption of reconsolidation process on the expression of learned fear responses. We demonstrate that extinction training with a single-paired cue resulted in cue-specific attenuation of fear responses but responses to other cures were unchanged. The cue-specific nature of the extinction persisted despite training sessions combined with D-cycloserine treatment reveals a significant weakness in extinction-based treatment. In contrast, the inhibition of the dorsal hippocampus (DH) but not the basolateral amygdala (BLA)-dependent memory reconsolidation process using either protein synthesis inhibitors or genetic disruption of cAMP-response-element-binding protein-mediated transcription comprehensively disrupted the learned connections between fear responses and all paired environmental cues. These findings emphasize the distinct role of the DH and the BLA in the reconsolidation process of fear memories and further indicate that the disruption of memory reconsolidation process in the DH may result in generalization of fear inhibition.

Conditioned aversion of aluminum sulfate in black ducks

USGS Publications Warehouse

Sparling, D.W.

1990-01-01

Three experiments were conducted to determine if reduced consumption of foods with elevated Al levels by black ducks (Anas rubripes) was due to taste aversion, conditioned taste aversion or malaise. Black ducks preferred a diet with 1,000 ppm Al over a control diet but ate less of a diet with 5,000 ppm Al. Prior experience with the high Al diet enhanced preference for the control diet. Changes in body weight and food consumption through time suggested that aversion to the high Al diet was a conditioned response to mild malaise.

Pharmacological interference with metabotropic glutamate receptor subtype 7 but not subtype 5 differentially affects within- and between-session extinction of Pavlovian conditioned fear.

PubMed

Toth, Iulia; Dietz, Monika; Peterlik, Daniel; Huber, Sabine E; Fendt, Markus; Neumann, Inga D; Flor, Peter J; Slattery, David A

2012-03-01

Fear extinction is defined as the attenuation of a conditioned-fear memory by re-exposing animals to the conditioned stimulus without the aversive stimulus. This process is known to be effectively enhanced via administration of D-cycloserine (DCS), a partial NMDA-receptor agonist. However, other glutamatergic mechanisms, such as interference with metabotropic glutamate receptor (mGluR) subtypes 5 and 7 in the extinction of aversive memories are insufficiently understood. Using the allosteric mGluR5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), the mGluR7 allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), and DCS for comparison, we aimed to study how pharmacological blockade of mGluR5 and activation of mGluR7 influenced within- and between-session conditioned-fear extinction training and extinction retention in rats. We show that when injected before extinction training, mGluR7 activation with AMN082 enhanced freezing and thereby attenuated within-session fear extinction, whereas both DCS and the mGluR5 receptor antagonist MPEP had no effect on this process. However, these differential drug effects were not long lasting, as no difference in extinction retention were observed 24 h later. Therefore, we assessed whether the compounds affect 24 h consolidation of extinction training following incomplete extinction training (between-session extinction). Similar to DCS, AMN082- but not MPEP-treated rats showed facilitated extinction retention, as exhibited by decreased freezing. Finally, using fluoxetine, we provide evidence that the effect of AMN082 on between-session extinction retention is most likely not via increasing 5-HT transmission. These findings demonstrate that mGluR7 activation differentially modulates conditioned-fear extinction, in dependence on the protocol employed, and suggests drugs with AMN082-like mechanisms as potential add-on drugs following exposure-based psychotherapy for fear-related human disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Age-dependent MDPV-induced taste aversions and thermoregulation in adolescent and adult rats.

PubMed

Merluzzi, Andrew P; Hurwitz, Zachary E; Briscione, Maria A; Cobuzzi, Jennifer L; Wetzell, Bradley; Rice, Kenner C; Riley, Anthony L

2014-07-01

Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of "bath salts," the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8, or 3.2 mg/kg), a common constituent in "bath salts," in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population. © 2013 Wiley Periodicals, Inc.

Developmental differences in aversive conditioning, extinction, and reinstatement: A study with children, adolescents, and adults.

PubMed

Waters, Allison M; Theresiana, Cindy; Neumann, David L; Craske, Michelle G

2017-07-01

This study investigated developmental differences in aversive conditioning, extinction, and reinstatement (i.e., the recovery of conditioned aversive associations following reexposure to the unconditioned stimulus [US] post-extinction). This study examined these mechanisms in children (M age =8.8years), adolescents (M age =16.1years), and adults (M age =32.3years) using differential aversive conditioning with a geometric shape conditional stimulus (CS+) paired with an aversive sound US and another shape (CS-) presented alone. Following an extinction phase in which both CSs were presented alone, half of the participants in each age group received three US exposures (reinstatement condition) and the other half did not (control condition), followed by all participants completing an extinction retest phase on the same day. Findings indicated (a) significant differences in generalizing aversive expectancies to safe stimuli during conditioning and extinction that persisted during retest in children relative to adults and adolescents, (b) significantly less positive CS reevaluations during extinction that persisted during retest in adolescents relative to adults and children, and (c) reinstatement of US expectancies to the CS+ relative to the CS- in all age groups. Results suggest important differences in stimulus safety learning in children and stimulus valence reevaluation in adolescents relative to adults. Copyright © 2017 Elsevier Inc. All rights reserved.

The enigma of conditioned taste aversion learning: stimulus properties of 2-phenylethylamine derivatives.

PubMed

Greenshaw, A J; Turrkish, S; Davis, B A

2002-01-01

The functional aversive stimulus properties of several IP doses of (+/-)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg-1) were measured with the conditioned taste aversion (CTA) paradigm. A two-bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (+/-)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (+/-)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (+/-)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (+/-)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives.

Rapid prefrontal cortex activation towards aversively paired faces and enhanced contingency detection are observed in highly trait-anxious women under challenging conditions

PubMed Central

Rehbein, Maimu Alissa; Wessing, Ida; Zwitserlood, Pienie; Steinberg, Christian; Eden, Annuschka Salima; Dobel, Christian; Junghöfer, Markus

2015-01-01

Relative to healthy controls, anxiety-disorder patients show anomalies in classical conditioning that may either result from, or provide a risk factor for, clinically relevant anxiety. Here, we investigated whether healthy participants with enhanced anxiety vulnerability show abnormalities in a challenging affective-conditioning paradigm, in which many stimulus-reinforcer associations had to be acquired with only few learning trials. Forty-seven high and low trait-anxious females underwent MultiCS conditioning, in which 52 different neutral faces (CS+) were paired with an aversive noise (US), while further 52 faces (CS−) remained unpaired. Emotional learning was assessed by evaluative (rating), behavioral (dot-probe, contingency report), and neurophysiological (magnetoencephalography) measures before, during, and after learning. High and low trait-anxious groups did not differ in evaluative ratings or response priming before or after conditioning. High trait-anxious women, however, were better than low trait-anxious women at reporting CS+/US contingencies after conditioning, and showed an enhanced prefrontal cortex (PFC) activation towards CS+ in the M1 (i.e., 80–117 ms) and M170 time intervals (i.e., 140–160 ms) during acquisition. These effects in MultiCS conditioning observed in individuals with elevated trait anxiety are consistent with theories of enhanced conditionability in anxiety vulnerability. Furthermore, they point towards increased threat monitoring and detection in highly trait-anxious females, possibly mediated by alterations in visual working memory. PMID:26113814

NMDA or 5-HT receptor antagonists impair memory reconsolidation and induce various types of amnesia.

PubMed

Nikitin, V P; Solntseva, S V; Kozyrev, S A; Nikitin, P V; Shevelkin, A V

2018-06-01

Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning. During the early period of amnesia (<10th day), the unpaired presentation of conditioned stimuli (CS) or unconditioned stimuli (US) in the same training context did not have an effect on both types of amnesia. Retraining an on 1st or 3rd day of amnesia induction facilitated memory formation, i.e. the number of CS + US pairings was lower than at initial training. On the 10th or 30th day after the MET/reminder, the number of CS + US pairings did not change between initial training and retraining. Retraining on the 10th or 30th day following the MK-801/reminder in the same or a new context of learning resulted in short, but not long-term, memory, and the number of CS + US pairings was higher than at the initial training. This type of amnesia was specific to the CS we used at initial training, since long-term memory for another kind of CS could be formed in the same snails. The attained results suggest that disruption of memory reconsolidation using antagonists of serotonin or NMDA glutamate receptors induced amnesias with different abilities to form long-term memory during the late period of development. Copyright © 2018 Elsevier B.V. All rights reserved.

Prenatal exposure to valproic acid disturbs the enkephalinergic system functioning, basal hedonic tone, and emotional responses in an animal model of autism.

PubMed

Schneider, Tomasz; Ziòłkowska, Barbara; Gieryk, Agnieszka; Tyminska, Anna; Przewłocki, Ryszard

2007-09-01

It has been suggested that behavioral aberrations observed in autism could be the result of dysfunction of the neuroregulatory role performed by the endogenous opioid peptides. Many of those aberrations have been recently modeled in rats exposed to valproic acid (VPA) on the 12th day of gestation (VPA rats). The aim of the present study was to elucidate functioning of the enkephalinergic system, one of the endogenous opioid peptide systems strongly involved in emotional responses, in VPA rats using both biochemical and behavioral methods. In situ hybridization was used to measure proenkephalin mRNA expression in adult VPA rats' central nucleus of the amygdala, the dorsal striatum, and the nucleus accumbens. Additional groups of animals were examined in a conditioned place aversion to naloxone, the elevated plus maze, and object recognition tests to assess their basal hedonic tone, anxiety, learning and memory, respectively. Prenatal exposure to VPA decreased proenkephalin mRNA expression in the dorsal striatum and the nucleus accumbens but not in the central nucleus of the amygdala. It also increased anxiety and attenuated conditioned place aversion to naloxone but had no impact on learning and memory. The present results suggest that prenatal exposure to VPA may lead to the decreased activity of the striatal enkephalinergic system and in consequence to increased anxiety and disregulated basal hedonic tone observed in VPA rats. Presented results are discussed in light of interactions between enkephalinergic, GABAergic, and dopaminergic systems in the striatum and mesolimbic areas of the brain.

Interactions between radiation and amphetamine in taste-aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1987-01-01

Three experiments were run to assess the role of the area postrema in taste-aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning to intact ratsmore » and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less-severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste-aversion learning may involve area post-remamediated mechanisms, particularly at the lower doses, but an intact area postrema is not a necessary condition of the acquisition of an amphetamine-induced taste aversion.« less

Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1987-08-01

Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intactmore » rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion.« less

Ethanol-induced conditioned taste aversion in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats.

PubMed

Dyr, Wanda; Wyszogrodzka, Edyta; Paterak, Justyna; Siwińska-Ziółkowska, Agnieszka; Małkowska, Anna; Polak, Piotr

2016-03-01

The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post-conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post-conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Emotional memory: No source memory without old-new recognition.

PubMed

Bell, Raoul; Mieth, Laura; Buchner, Axel

2017-02-01

Findings reported in the memory literature suggest that the emotional components of an encoding episode can be dissociated from nonemotional memory. In particular, it has been found that the previous association with threatening events can be retrieved in aversive conditioning even in the absence of item identification. In the present study, we test whether emotional source memory can be independent of item recognition. Participants saw pictures of snakes paired with threatening and nonthreatening context information (poisonousness or nonpoisonousness). In the source memory test, participants were required to remember whether a snake was associated with poisonousness or nonpoisonousness. A simple extension of a well-established multinomial source monitoring model was used to measure source memory for unrecognized items. By using this model, it was possible to assess directly whether participants were able to associate a previously seen snake with poisonousness or nonpoisonousness even if the snake itself was not recognized as having been presented during the experiment. In 3 experiments, emotional source memory was only found for recognized items. While source memory for recognized items differed between emotional and nonemotional information, source memory for unrecognized items was equally absent for emotional and nonemotional information. We conclude that emotional context information is bound to item representations and cannot be retrieved in the absence of item recognition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Ontogeny of Contextual Fear Memory Formation, Specificity, and Persistence in Mice

ERIC Educational Resources Information Center

Akers, Katherine G.; Arruda-Carvalho, Maithe; Josselyn, Sheena A.; Frankland, Paul W.

2012-01-01

Pinpointing the precise age when young animals begin to form memories of aversive events is valuable for understanding the onset of anxiety and mood disorders and for detecting early cognitive impairment in models of childhood-onset disorders. Although these disorders are most commonly modeled in mice, we know little regarding the development of…

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

[The consolidation of memory, one century on].

PubMed

Prado-Alcala, R A; Quirarte, G L

The theory of memory consolidation, based on the work published by Georg Elias Muller and Alfons Pilzecker over a century ago, continues to guide research into the neurobiology of memory, either directly or indirectly. In their classic monographic work, they concluded that fixing memory requires the passage of time (consolidation) and that memory is vulnerable during this period of consolidation, as symptoms of amnesia appear when brain functioning is interfered with before the consolidation process is completed. Most of the experimental data concerning this phenomenon strongly support the theory. In this article we present a review of experiments that have made it possible to put forward a model that explains the amnesia produced in conventional learning conditions, as well as another model related to the protection of memory when the same instances of learning are submitted to a situation involving intensive training. Findings from relatively recent studies have shown that treatments that typically produce amnesia when they are administered immediately after a learning experience (during the period in which the memory would be consolidating itself) no longer have any effect when the instances of learning involve a relatively large number of trials or training sessions, or relatively high intensity aversive events. These results are not congruent with the prevailing theories about consolidation.

Burying by rats in response to aversive and nonaversive stimuli

PubMed Central

Poling, Alan; Cleary, James; Monaghan, Michael

1981-01-01

Previous investigations have shown that rats bury a variety of conditioned and unconditioned aversive stimuli. Such burying has been considered as a species-typical defensive reaction. In the present studies, rats buried spouts filled with Tabasco sauce, or condensed milk to which a taste aversion was conditioned, but did not bury water-filled spouts or spouts filled with a palatable novel food (apple juice) to which a taste aversion was not conditioned. However, in other experiments rats consistently and repeatedly buried Purina Rat Chow, Purina Rat Chow coated with quinine, and glass marbles. This indicates that a variety of stimuli, not all aversive or novel, evoke burying by rats. Whereas the behavior may reasonably be considered as a species-typical defensive behavior in some situations, the wide range of conditions that occasion burying suggests that the behavior has no single biological function. PMID:16812198

Conditioned taste aversion, drugs of abuse and palatability

PubMed Central

Lin, Jian-You; Arthurs, Joe; Reilly, Steve

2014-01-01

LIN, J.-Y., J. Arthurs and S. Reilly. Conditioned taste aversion: Palatability and drugs of abuse. NEUROSCI BIOBEHAV REV XX(x) XXX-XXX, 2014. – We consider conditioned taste aversion to involve a learned reduction in the palatability of a taste (and hence in amount consumed) based on the association that develops when a taste experience is followed by gastrointestinal malaise. The present article evaluates the well-established finding that drugs of abuse, at doses that are otherwise considered rewarding and self-administered, cause intake suppression. Our recent work using lick pattern analysis shows that drugs of abuse also cause a palatability downshift and, therefore, support conditioned taste aversion learning. PMID:24813806

Effects of pharmacological manipulation of the kappa opioid receptors on the aversive effects of nicotine.

PubMed

Ward, Melissa; Norman, Haval; D'Souza, Manoranjan S

2018-02-15

Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified. In this study, we evaluated the role of kappa opioid receptors (KORs) in the aversive effects of nicotine (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion (CTA) model in Wistar rats. The KORs were activated using the selective KOR agonist (±)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate groups of rats using a between-subjects design. Pretreatment with the KOR agonist (±)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine-associated solution. Additionally, (±)U-50,488H (0.3mg/kg) on its own induced aversion to the flavored solution associated with it even in the absence of nicotine, suggesting that the KOR agonist induced increase in nicotine-induced aversion was an additive effect. Interestingly, administration of the KOR antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not after conditioning with nicotine/saline, attenuated nicotine-induced aversive effects compared to saline controls. Taken together, these data suggest a role for KORs in the aversive effects of nicotine. Copyright © 2017 Elsevier B.V. All rights reserved.

Visuocortical Changes During Delay and Trace Aversive Conditioning: Evidence From Steady-State Visual Evoked Potentials

PubMed Central

Miskovic, Vladimir; Keil, Andreas

2015-01-01

The visual system is biased towards sensory cues that have been associated with danger or harm through temporal co-occurrence. An outstanding question about conditioning-induced changes in visuocortical processing is the extent to which they are driven primarily by top-down factors such as expectancy or by low-level factors such as the temporal proximity between conditioned stimuli and aversive outcomes. Here, we examined this question using two different differential aversive conditioning experiments: participants learned to associate a particular grating stimulus with an aversive noise that was presented either in close temporal proximity (delay conditioning experiment) or after a prolonged stimulus-free interval (trace conditioning experiment). In both experiments we probed cue-related cortical responses by recording steady-state visual evoked potentials (ssVEPs). Although behavioral ratings indicated that all participants successfully learned to discriminate between the grating patterns that predicted the presence versus absence of the aversive noise, selective amplification of population-level responses in visual cortex for the conditioned danger signal was observed only when the grating and the noise were temporally contiguous. Our findings are in line with notions purporting that changes in the electrocortical response of visual neurons induced by aversive conditioning are a product of Hebbian associations among sensory cell assemblies rather than being driven entirely by expectancy-based, declarative processes. PMID:23398582

Nicotine-induced conditioned taste aversion in the rat: effects of ethanol.

PubMed

Korkosz, Agnieszka; Scinska, Anna; Taracha, Ewa; Plaznik, Adam; Kukwa, Andrzej; Kostowski, Wojciech; Bienkowski, Przemyslaw

2006-05-10

It has been shown that small doses of ethanol antagonise the discriminative stimulus properties of nicotine in the rat. The aim of the present study was to evaluate whether ethanol could antagonise the aversive stimulus effects of nicotine. Wistar rats were trained to associate nicotine injections with a novel tasting fluid (0.1% saccharin) in the conditioned taste aversion procedure. Nicotine (0.3 mg/kg, s.c.) was injected 5 min after the end of a 20-min exposure to the saccharin solution. Ethanol (0.25-0.5 g/kg, i.p.) was administered 5 or 50 min before nicotine. In general, ethanol did not inhibit nicotine-induced conditioned taste aversion. Contrary to the findings in drug discrimination studies, a slight but significant enhancement of nicotine-induced taste aversion conditioning was observed after ethanol pre-treatment. Blood ethanol levels were measured in a separate group of rats. Maximal blood ethanol levels after i.p. administration of 0.25 or 0.5 g/kg ethanol exceeded 20 and 80 mg%, respectively. Concluding, the present results may indicate that ethanol does not attenuate nicotine-induced conditioned taste aversion in the rat.

Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens.

PubMed

Sellings, Laurie H L; Baharnouri, Golriz; McQuade, Lindsey E; Clarke, Paul B S

2008-07-01

Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.

Does Conspecific Fighting Yield Conditioned Taste Aversion in Rats?

ERIC Educational Resources Information Center

Nakajima, Sadahiko; Kumazawa, Gaku; Ieki, Hayato; Hashimoto, Aya

2012-01-01

Running in an activity wheel yields conditioned aversion to a taste solution consumed before the running, but its underlying physiological mechanism is unknown. According to the claim that energy expenditure or general stress caused by physical exercise is a critical factor for this taste-aversion learning, not only running but also other…

Risk Aversion is Associated with Decision Making among Community-Based Older Persons

PubMed Central

Boyle, Patricia A.; Yu, Lei; Buchman, Aron S.; Bennett, David A.

2012-01-01

Background: Risk aversion is associated with many important decisions among younger and middle aged persons, but the association of risk aversion with decision making has not been well studied among older persons who face some of the most significant decisions of their lives. Method: Using data from 606 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging, we examined the association of risk aversion with decision making. Risk aversion was measured using standard behavioral economics questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing; potential gamble gains ranged from $20 to $300 with the gain amounts varied randomly over questions. Decision making was measured using a 12 item version of the Decision Making Competence Assessment Tool. Findings: In a linear regression model adjusted for age, sex, education, and income, greater risk aversion was associated with poorer decision making [estimate = −1.03, standard error (SE) = 0.35, p = 0.003]. Subsequent analyses showed that the association of risk aversion with decision making persisted after adjustment for global cognitive function as well as executive and non-executive cognitive abilities. Conclusion: Similar to findings from studies of younger persons, risk aversion is associated with poorer decision making among older persons who face a myriad of complex and influential decisions. PMID:22754545

Risk Aversion is Associated with Decision Making among Community-Based Older Persons.

PubMed

Boyle, Patricia A; Yu, Lei; Buchman, Aron S; Bennett, David A

2012-01-01

Risk aversion is associated with many important decisions among younger and middle aged persons, but the association of risk aversion with decision making has not been well studied among older persons who face some of the most significant decisions of their lives. Using data from 606 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal epidemiologic study of aging, we examined the association of risk aversion with decision making. Risk aversion was measured using standard behavioral economics questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing; potential gamble gains ranged from $20 to $300 with the gain amounts varied randomly over questions. Decision making was measured using a 12 item version of the Decision Making Competence Assessment Tool. In a linear regression model adjusted for age, sex, education, and income, greater risk aversion was associated with poorer decision making [estimate = -1.03, standard error (SE) = 0.35, p = 0.003]. Subsequent analyses showed that the association of risk aversion with decision making persisted after adjustment for global cognitive function as well as executive and non-executive cognitive abilities. Similar to findings from studies of younger persons, risk aversion is associated with poorer decision making among older persons who face a myriad of complex and influential decisions.

The touchscreen operant platform for testing learning and memory in rats and mice.

PubMed

Horner, Alexa E; Heath, Christopher J; Hvoslef-Eide, Martha; Kent, Brianne A; Kim, Chi Hun; Nilsson, Simon R O; Alsiö, Johan; Oomen, Charlotte A; Holmes, Andrew; Saksida, Lisa M; Bussey, Timothy J

2013-10-01

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: visual discrimination, object-location paired-associates learning, visuomotor conditional learning and autoshaping. It is accompanied by two further protocols (also published in this issue) that use the touchscreen platform to assess executive function, working memory and pattern separation.

A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.

PubMed

Eddy, Meghan C; Eschle, Benjamin K; Peterson, Darlene; Lauras, Nathan; Margolskee, Robert F; Delay, Eugene R

2012-06-01

Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.

Odor Preference Learning and Memory Modify GluA1 Phosphorylation and GluA1 Distribution in the Neonate Rat Olfactory Bulb: Testing the AMPA Receptor Hypothesis in an Appetitive Learning Model

ERIC Educational Resources Information Center

Cui, Wen; Darby-King, Andrea; Grimes, Matthew T.; Howland, John G.; Wang, Yu Tian; McLean, John H.; Harley, Carolyn W.

2011-01-01

An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in…

Classical conditioning through auditory stimuli in Drosophila: methods and models

PubMed Central

Menda, Gil; Bar, Haim Y.; Arthur, Ben J.; Rivlin, Patricia K.; Wyttenbach, Robert A.; Strawderman, Robert L.; Hoy, Ronald R.

2011-01-01

SUMMARY The role of sound in Drosophila melanogaster courtship, along with its perception via the antennae, is well established, as is the ability of this fly to learn in classical conditioning protocols. Here, we demonstrate that a neutral acoustic stimulus paired with a sucrose reward can be used to condition the proboscis-extension reflex, part of normal feeding behavior. This appetitive conditioning produces results comparable to those obtained with chemical stimuli in aversive conditioning protocols. We applied a logistic model with general estimating equations to predict the dynamics of learning, which successfully predicts the outcome of training and provides a quantitative estimate of the rate of learning. Use of acoustic stimuli with appetitive conditioning provides both an alternative to models most commonly used in studies of learning and memory in Drosophila and a means of testing hearing in both sexes, independently of courtship responsiveness. PMID:21832129

Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

DTIC Science & Technology

2009-09-01

startle amplitude. They then received Pavlovian fear conditioning of five pairings of a 3 s light co-terminating with a 500 ms, 0.6mA footshock. Four...Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats PRINCIPAL INVESTIGATOR: Jeffrey B. Rosen, Ph.D...NUMBER Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats 5b. GRANT

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

NASA Technical Reports Server (NTRS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2003-01-01

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

G(o) Activation Is Required for Both Appetitive and Aversive Memory Acquisition in "Drosophila"

ERIC Educational Resources Information Center

Madalan, Adrian; Yang, Xiao; Ferris, Jacob; Zhang, Shixing; Roman, Gregg

2012-01-01

Heterotrimeric G(o) is an abundant brain protein required for negatively reinforced short-term associative olfactory memory in "Drosophila". G(o) is the only known substrate of the S1 subunit of pertussis toxin (PTX) in fly, and acute expression of PTX within the mushroom body neurons (MB) induces a reversible deficit in associative olfactory…

Modulation of the N170 with Classical Conditioning: The Use of Emotional Imagery and Acoustic Startle in Healthy and Depressed Participants

PubMed Central

Camfield, David A.; Mills, Jessica; Kornfeld, Emma J.; Croft, Rodney J.

2016-01-01

Recent studies have suggested that classical conditioning may be capable of modulating early sensory processing in the human brain, and that there may be differences in the magnitude of the conditioned changes for individuals with major depressive disorder. The effect of conditioning on the N170 event-related potential was investigated using neutral faces as conditioned stimuli (CS+) and emotional imagery and acoustic startle as unconditioned stimuli (UCS). In the first experiment, electroencephalogram was recorded from 24 undergraduate students (M = 21.07 years, SD = 3.38 years) under the following conditions: (i) CS+/aversive imagery, (ii) CS+/aversive imagery and acoustic startle, (iii) CS+/acoustic startle, and (iv) CS+/pleasant imagery. The amplitude of the N170 was enhanced following conditioning with aversive imagery as well as acoustic startle. In the second experiment, 26 healthy control participants were tested (17 females and 9 males, age M = 25.97 years, SD = 9.42) together with 18 depressed participants (13 females and 5 males, age M = 23.26 years, SD = 4.01) and three conditions were used: CS+/aversive imagery, CS+/pleasant imagery, and CS-. N170 amplitude at P7 was increased for the CS+/aversive condition in comparison to CS- in the conditioning blocks versus baseline. No differences between depressed and healthy participants were found. Across both experiments, evaluative conditioning was absent. It was concluded that aversive UCS are capable of modulating early sensory processing of faces, although further research is also warranted in regards to positive UCS. PMID:27445773

Hippocampal Activation of Rac1 Regulates the Forgetting of Object Recognition Memory.

PubMed

Liu, Yunlong; Du, Shuwen; Lv, Li; Lei, Bo; Shi, Wei; Tang, Yikai; Wang, Lianzhang; Zhong, Yi

2016-09-12

Forgetting is a universal feature for most types of memories. The best-defined and extensively characterized behaviors that depict forgetting are natural memory decay and interference-based forgetting [1, 2]. Molecular mechanisms underlying the active forgetting remain to be determined for memories in vertebrates. Recent progress has begun to unravel such mechanisms underlying the active forgetting [3-11] that is induced through the behavior-dependent activation of intracellular signaling pathways. In Drosophila, training-induced activation of the small G protein Rac1 mediates natural memory decay and interference-based forgetting of aversive conditioning memory [3]. In mice, the activation of photoactivable-Rac1 in recently potentiated spines in a motor learning task erases the motor memory [12]. These lines of evidence prompted us to investigate a role for Rac1 in time-based natural memory decay and interference-based forgetting in mice. The inhibition of Rac1 activity in hippocampal neurons through targeted expression of a dominant-negative Rac1 form extended object recognition memory from less than 72 hr to over 72 hr, whereas Rac1 activation accelerated memory decay within 24 hr. Interference-induced forgetting of this memory was correlated with Rac1 activation and was completely blocked by inhibition of Rac1 activity. Electrophysiological recordings of long-term potentiation provided independent evidence that further supported a role for Rac1 activation in forgetting. Thus, Rac1-dependent forgetting is evolutionarily conserved from invertebrates to vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

PubMed

Jing Li, Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

2018-05-09

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1-2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. SIGNIFICANCE STATEMENT Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex (PFC), may differentially control acquisition or recall of fear memories and how these mechanisms might regulate sensitivity to the rewarding effects of opioids. We demonstrate that PFC D4 activation not only controls the salience of fear memory acquisition, but potentiates the rewarding effects of opioids. In contrast, PFC D1 receptor activation blocks recall of fear memories and prevents potentiation of opioid reward effects. Together, these findings demonstrate novel PFC mechanisms that may account for how emotional memory disturbances might increase the addictive liability of opioid-class drugs. Copyright © 2018 the authors 0270-6474/18/384543-13$15.00/0.

Explicit Disassociation of a Conditioned Stimulus and Unconditioned Stimulus during Extinction Training Reduces Both Time to Asymptotic Extinction and Spontaneous Recovery of a Conditioned Taste Aversion

ERIC Educational Resources Information Center

Mickley, G. Andrew; DiSorbo, Anthony; Wilson, Gina N.; Huffman, Jennifer; Bacik, Stephanie; Hoxha, Zana; Biada, Jaclyn M.; Kim, Ye-Hyun

2009-01-01

Conditioned taste aversions (CTAs) may be acquired when an animal consumes a novel taste (CS) and then experiences the symptoms of poisoning (US). This aversion may be extinguished by repeated exposure to the CS alone. However, following a latency period in which the CS is not presented, the CTA will spontaneously recover (SR). In the current…

Emotion Causes Targeted Forgetting of Established Memories

PubMed Central

Strange, Bryan A.; Kroes, Marijn C. W.; Fan, Judith E.; Dolan, Raymond J.

2010-01-01

Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval. PMID:21191439

Emotion causes targeted forgetting of established memories.

PubMed

Strange, Bryan A; Kroes, Marijn C W; Fan, Judith E; Dolan, Raymond J

2010-01-01

Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

Cue-Induced Ethanol Seeking in Drosophila melanogaster Is Dose-Dependent

PubMed Central

Nunez, Kavin M.; Azanchi, Reza; Kaun, Karla R.

2018-01-01

Alcohol use disorder generates devastating social, medical and economic burdens, making it a major global health issue. The persistent nature of memories associated with intoxication experiences often induces cravings and triggers relapse in recovering individuals. Despite recent advances, the neural and molecular mechanisms underlying these memories are complex and not well understood. This makes finding effective pharmacological targets challenging. The investigation of persistent alcohol-associated memories in the fruit fly, Drosophila melanogaster, presents a unique opportunity to gain a comprehensive understanding of the memories for ethanol reward at the level of genes, molecules, neurons and circuits. Here we characterize the dose-dependent nature of ethanol on the expression of memory for an intoxication experience. We report that the concentration of ethanol, number of ethanol exposures, length of ethanol exposures, and timing between ethanol exposures are critical in determining whether ethanol is perceived as aversive or appetitive, and in how long the memory for the intoxicating properties of ethanol last. Our study highlights that fruit flies display both acute and persistent memories for ethanol-conditioned odor cues, and that a combination of parameters that determine the intoxication state of the fly influence the seemingly complex retention and expression of memories associated with intoxication. Our thorough behavioral characterization provides the opportunity to interrogate the biological underpinnings of these observed preference differences in future studies. PMID:29740347

Fasting launches CRTC to facilitate long-term memory formation in Drosophila.

PubMed

Hirano, Yukinori; Masuda, Tomoko; Naganos, Shintaro; Matsuno, Motomi; Ueno, Kohei; Miyashita, Tomoyuki; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-25

Canonical aversive long-term memory (LTM) formation in Drosophila requires multiple spaced trainings, whereas appetitive LTM can be formed after a single training. Appetitive LTM requires fasting prior to training, which increases motivation for food intake. However, we found that fasting facilitated LTM formation in general; aversive LTM formation also occurred after single-cycle training when mild fasting was applied before training. Both fasting-dependent LTM (fLTM) and spaced training-dependent LTM (spLTM) required protein synthesis and cyclic adenosine monophosphate response element-binding protein (CREB) activity. However, spLTM required CREB activity in two neural populations--mushroom body and DAL neurons--whereas fLTM required CREB activity only in mushroom body neurons. fLTM uses the CREB coactivator CRTC, whereas spLTM uses the coactivator CBP. Thus, flies use distinct LTM machinery depending on their hunger state.

Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

PubMed

Mendoza, J; Sanio, C; Chaudhri, N

2015-02-01

The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of NPY in learning and memory.

PubMed

Gøtzsche, C R; Woldbye, D P D

2016-02-01

High levels of NPY expression in brain regions important for learning and memory together with its neuromodulatory and neurotrophic effects suggest a regulatory role for NPY in memory processes. Therefore it is not surprising that an increasing number of studies have provided evidence for NPY acting as a modulator of neuroplasticity, neurotransmission, and memory. Here these results are presented in relation to the types of memory affected by NPY and its receptors. NPY can exert both inhibitory and stimulatory effects on memory, depending on memory type and phase, dose applied, brain region, and NPY receptor subtypes. Thus NPY act as a resilience factor by impairing associative implicit memory after stressful and aversive events, as evident in models of fear conditioning, presumably via Y1 receptors in the amygdala and prefrontal cortex. In addition, NPY impairs acquisition but enhances consolidation and retention in models depending on spatial and discriminative types of associative explicit memory, presumably involving Y2 receptor-mediated regulations of hippocampal excitatory transmission. Moreover, spatial memory training leads to increased hippocampal NPY gene expression that together with Y1 receptor-mediated neurogenesis could constitute necessary steps in consolidation and long-term retention of spatial memory. Altogether, NPY-induced effects on learning and memory seem to be biphasic, anatomically and temporally differential, and in support of a modulatory role of NPY at keeping the system in balance. Obtaining further insight into memory-related effects of NPY could inspire the engineering of new therapeutics targeting diseases where impaired learning and memory are central elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

An unconditioned stimulus retrieval extinction procedure to prevent the return of fear memory.

PubMed

Liu, Jianfeng; Zhao, Liyan; Xue, Yanxue; Shi, Jie; Suo, Lin; Luo, Yixiao; Chai, Baisheng; Yang, Chang; Fang, Qin; Zhang, Yan; Bao, Yanping; Pickens, Charles L; Lu, Lin

2014-12-01

Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Examining the sex- and circadian dependency of a learning phenotype in mice with glycine transporter 1 deletion in two Pavlovian conditioning paradigms

PubMed Central

Dubroqua, Sylvain; Boison, Detlev; Feldon, Joram; Möhler, Hanns; Yee, Benjamin K.

2011-01-01

Behavioural characterisation of transgenic mice has been instrumental in search of therapeutic targets for the modulation of cognitive function. However, little effort has been devoted to phenotypic characterisation across environmental conditions and genomic differences such as sex and strain, which is essential to translational research. The present study is an effort in this direction. It scrutinised the stability and robustness of the phenotype of enhanced Pavlovian conditioning reported in mice with forebrain neuronal deletion of glycine transporter 1 by evaluating the possible presence of sex and circadian dependency, and its consistency across aversive and appetitive conditioning paradigms. The Pavlovian phenotype was essentially unaffected by the time of testing between the two circadian phases, but it was modified by sex in both conditioning paradigms. We observed that the effect size of the phenotype was strongest in female mice tested during the dark phase in the aversive paradigm. Critically, the presence of the phenotype in female mutants was accompanied by an increase in resistance to extinction. Similarly, enhanced conditioned responding once again emerged solely in female mutants in the appetitive conditioning experiment, which was again associated with an increased resistance to extinction across days, but male mutants exhibited an opposite trend towards facilitation of extinction. The present study has thus added hitherto unknown qualifications and specifications of a previously reported memory enhancing phenotype in this mouse line by identifying the determinants of the magnitude and direction of the expressed phenotype. This in-depth comparative approach is of value to the interpretation of behavioural findings in general. PMID:21596148

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain.

PubMed

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca(2+) indicator in the MBs, we investigated synaptic transmission and plasticity at the AL-MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca(2+) responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca(2+) responses were mediated through Drosophila NMDA receptors (dNRs). AL-MB synaptic transmission was enhanced more than 2 h after the simultaneous 'associative-stimulation' of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL-MB synapses but not at the AFV-MB synapses. AL-MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL-MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL-MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL-MB LTE might be a relevant cellular model for olfactory memory.

Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain

PubMed Central

Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-01

In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca2+ indicator in the MBs, we investigated synaptic transmission and plasticity at the AL–MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca2+ responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca2+ responses were mediated through Drosophila NMDA receptors (dNRs). AL–MB synaptic transmission was enhanced more than 2 h after the simultaneous ‘associative-stimulation’ of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL–MB synapses but not at the AFV–MB synapses. AL–MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL–MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL–MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL–MB LTE might be a relevant cellular model for olfactory memory. PMID:23027817

Effects of dietary choline availability on latent inhibition of flavor aversion learning.

PubMed

Gámiz, Fernando; Recio, Sergio Andrés; Iliescu, Adela Florentina; Gallo, Milagros; de Brugada, Isabel

2015-08-01

It has been previously reported that dietary choline supplementation might affect latent inhibition (LI) using a conditioned suppression procedure in rats. We have assessed the effect of dietary choline on LI of flavor aversion learning. Adult male Wistar rats received a choline supplemented (5 g/kg), deficient (0 g/kg), or standard (1.1 g/kg) diet for 3 months. After this supplementation period, all rats went through a conditioned taste aversion (CTA) procedure, half of them being pre-exposed to the conditioned stimulus before the conditioning. The results indicated that choline deficiency prevents LI of conditioned flavor aversion to cider vinegar (3%) induced by a LiCl (0.15 M; 2% body weight) intraperitoneal injection, while choline supplementation enhances CTA leading to slower extinction. The role of the brain systems modulating attentional processes is discussed.

Development of an aversive Pavlovian-to-instrumental transfer task in rat

PubMed Central

Campese, Vincent; McCue, Margaret; Lázaro-Muñoz, Gabriel; LeDoux, Joseph E.; Cain, Christopher K.

2013-01-01

Pavlovian-to-instrumental transfer (PIT) is an effect whereby a classically conditioned stimulus (CS) enhances ongoing instrumental responding. PIT has been extensively studied with appetitive conditioning but barely at all with aversive conditioning. Although it's been argued that conditioned suppression is a form of aversive PIT, this effect is fundamentally different from appetitive PIT because the CS suppresses, instead of facilitates, responding. Five experiments investigated the importance of a variety of factors on aversive PIT in a rodent Sidman avoidance paradigm in which ongoing shuttling behavior (unsignaled active avoidance or USAA) was facilitated by an aversive CS. Experiment 1 demonstrated a basic PIT effect. Experiment 2 found that a moderate amount of USAA extinction produces the strongest PIT with shuttling rates best at around 2 responses per minute prior to the CS. Experiment 3 tested a protocol in which the USAA behavior was required to reach the 2-response per minute mark in order to trigger the CS presentation and found that this produced robust and reliable PIT. Experiment 4 found that the Pavlovian conditioning US intensity was not a major determinant of PIT strength. Experiment 5 demonstrated that if the CS and US were not explicitly paired during Pavlovian conditioning, PIT did not occur, showing that CS-US learning is required. Together, these studies demonstrate a robust, reliable and stable aversive PIT effect that is amenable to analysis of neural circuitry. PMID:24324417

The role of risk aversion in non-conscious decision making.

PubMed

Wang, Shuo; Krajbich, Ian; Adolphs, Ralph; Tsuchiya, Naotsugu

2012-01-01

To what extent can people choose advantageously without knowing why they are making those choices? This hotly debated question has capitalized on the Iowa Gambling Task (IGT), in which people often learn to choose advantageously without appearing to know why. However, because the IGT is unconstrained in many respects, this finding remains debated and other interpretations are possible (e.g., risk aversion, ambiguity aversion, limits of working memory, or insensitivity to reward/punishment can explain the finding of the IGT). Here we devised an improved variant of the IGT in which the deck-payoff contingency switches after subjects repeatedly choose from a good deck, offering the statistical power of repeated within-subject measures based on learning the reward contingencies associated with each deck. We found that participants exhibited low confidence in their choices, as probed with post-decision wagering, despite high accuracy in selecting advantageous decks in the task, which is putative evidence for non-conscious decision making. However, such a behavioral dissociation could also be explained by risk aversion, a tendency to avoid risky decisions under uncertainty. By explicitly measuring risk aversion for each individual, we predicted subjects' post-decision wagering using Bayesian modeling. We found that risk aversion indeed does play a role, but that it did not explain the entire effect. Moreover, independently measured risk aversion was uncorrelated with risk aversion exhibited during our version of the IGT, raising the possibility that the latter risk aversion may be non-conscious. Our findings support the idea that people can make optimal choices without being fully aware of the basis of their decision. We suggest that non-conscious decision making may be mediated by emotional feelings of risk that are based on mechanisms distinct from those that support cognitive assessment of risk.

The Role of Risk Aversion in Non-Conscious Decision Making

PubMed Central

Wang, Shuo; Krajbich, Ian; Adolphs, Ralph; Tsuchiya, Naotsugu

2012-01-01

To what extent can people choose advantageously without knowing why they are making those choices? This hotly debated question has capitalized on the Iowa Gambling Task (IGT), in which people often learn to choose advantageously without appearing to know why. However, because the IGT is unconstrained in many respects, this finding remains debated and other interpretations are possible (e.g., risk aversion, ambiguity aversion, limits of working memory, or insensitivity to reward/punishment can explain the finding of the IGT). Here we devised an improved variant of the IGT in which the deck-payoff contingency switches after subjects repeatedly choose from a good deck, offering the statistical power of repeated within-subject measures based on learning the reward contingencies associated with each deck. We found that participants exhibited low confidence in their choices, as probed with post-decision wagering, despite high accuracy in selecting advantageous decks in the task, which is putative evidence for non-conscious decision making. However, such a behavioral dissociation could also be explained by risk aversion, a tendency to avoid risky decisions under uncertainty. By explicitly measuring risk aversion for each individual, we predicted subjects’ post-decision wagering using Bayesian modeling. We found that risk aversion indeed does play a role, but that it did not explain the entire effect. Moreover, independently measured risk aversion was uncorrelated with risk aversion exhibited during our version of the IGT, raising the possibility that the latter risk aversion may be non-conscious. Our findings support the idea that people can make optimal choices without being fully aware of the basis of their decision. We suggest that non-conscious decision making may be mediated by emotional feelings of risk that are based on mechanisms distinct from those that support cognitive assessment of risk. PMID:22375133

Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test)

PubMed Central

Schmitz, Anja; Grillon, Christian

2012-01-01

The threat of predictable and unpredictable aversive events was developed to assess short-duration (fear) and long-duration (anxiety) aversive states in humans. A typical experiment consists of three conditions: a safe condition (neutral (N)), during which participants are safe from aversive stimuli, and two threat conditions—one in which aversive events are administered predictably (P) (i.e., signaled by a threat cue), and one in which aversive stimuli are administered unpredictably (U). During the so-called NPU -threat test, ongoing change in aversive states is measured with the startle reflex. The NPU -threat test has been validated in pharmacological and clinical studies and can be implemented in children and adults. Similar procedures have been applied in animal models, making the NPU -threat test an ideal tool for translational research. The procedure is relatively short (35 min), simple to implement and generates consistent results with large effect sizes. PMID:22362158

Neural intrinsic connectivity networks associated with risk aversion in old age.

PubMed

Han, S Duke; Boyle, Patricia A; Arfanakis, Konstantinos; Fleischman, Debra A; Yu, Lei; Edmonds, Emily C; Bennett, David A

2012-02-01

Risk aversion is associated with several important real world outcomes. Although the neurobiological correlates of risk aversion have been studied in young persons, little is known of the neurobiological correlates of risk aversion among older persons. Resting-state functional MRI data were collected on 134 non-demented participants of the Rush Memory and Aging Project, a community-based cohort study of aging. Risk aversion was measured using a series of standard questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing, with potential gains varied across questions. Participants determined to be "high" (n=27) and "low" (n=27) in risk aversion were grouped accordingly. Using a spherical seed region of interest in the anterior cingulate cortex, voxel-wise functional connectivity network similarities were observed in bilateral frontal, anterior and posterior cingulate, insula, basal ganglia, temporal, parietal, and thalamic regions. Differences in functional connectivity were observed such that those low in risk aversion had greater connectivity to clusters in the superior, middle, and medial frontal regions, as well as cerebellar, parietal, occipital, and inferior temporal regions. Those high in risk aversion had greater connectivity to clusters in the inferior and orbital frontal, parahippocampal, and insula regions, as well as thalamic, parietal, precentral gyrus, postcentral gyrus, and middle temporal regions. Similarities and differences in functional connectivity patterns may reflect the historical recruitment of specific brain regions as a network in the active processing of risk in older adults. Copyright © 2011 Elsevier B.V. All rights reserved.

Neural Intrinsic Connectivity Networks Associated with Risk Aversion in Old Age

PubMed Central

Han, S. Duke; Boyle, Patricia A.; Arfanakis, Konstantinos; Fleischman, Debra A.; Yu, Lei; Edmonds, Emily C.; Bennett, David A.

2011-01-01

Risk aversion is associated with several important real world outcomes. Although the neurobiological correlates of risk aversion have been studied in young persons, little is known of the neurobiological correlates of risk aversion among older persons. Resting-state functional MRI data were collected on 134 non-demented participants of the Rush Memory and Aging Project, a community-based cohort study of aging. Risk aversion was measured using a series of standard questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing, with potential gains varied across questions. Participants determined to be “high” (n=27) and “low” (n=27) in risk aversion were grouped accordingly. Using a spherical seed region of interest in the anterior cingulate cortex, voxel-wise functional connectivity network similarities were observed in bilateral frontal, anterior and posterior cingulate, insula, basal ganglia, temporal, parietal, and thalamic regions. Differences in functional connectivity were observed such that those low in risk aversion had greater connectivity to clusters in the superior, middle, and medial frontal regions, as well as cerebellar, parietal, occipital, and inferior temporal regions. Those high in risk aversion had greater connectivity to clusters in the inferior and orbital frontal, parahippocampal, and insula regions, as well as thalamic, parietal, precentral gyrus, postcentral gyrus, and middle temporal regions. Similarities and differences in functional connectivity patterns may reflect the historical recruitment of specific brain regions as a network in the active processing of risk in older adults. PMID:22044475

Extinction of aversive classically conditioned human sexual response.

PubMed

Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Both, Stephanie

2015-04-01

Research has shown that acquired subjective likes and dislikes are quite resistant to extinction. Moreover, studies on female sexual response demonstrated that diminished genital arousal and positive affect toward erotic stimuli due to aversive classical conditioning did not extinguish during an extinction phase. Possible resistance to extinction of aversive conditioned sexual responses may have important clinical implications. However, resistance to extinction of aversive conditioned human sexual response has not been studied using extensive extinction trials. This article aims to study resistance to extinction of aversive conditioned sexual responses in sexually functional men and women. A differential conditioning experiment was conducted, with two erotic pictures as conditioned stimulus (CSs) and a painful stimulus as unconditioned stimuli (USs). Only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. Penile circumference and vaginal pulse amplitude were assessed, and ratings of affective value and subjective sexual arousal were obtained. Also, a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. Men and women rated the CS+ more negative as compared with the CS-. During the first trials of the extinction phase, vaginal pulse amplitude was lower in response to the CS+ than in response to the CS-, and on the first extinction trial women rated the CS+ as less sexually arousing. Intriguingly, men did not demonstrate attenuated genital and subjective sexual response. Aversive conditioning, by means of painful stimuli, only affects sexual responses in women, whereas it does not in men. Although conditioned sexual likes and dislikes are relatively persistent, conditioned affect eventually does extinguish. © 2014 International Society for Sexual Medicine.

Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

DTIC Science & Technology

1992-01-01

SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets

Acquisition of lithium chloride- and radiation-induced taste aversions in hypophysectomized rats.

PubMed

Rabin, B M; Hunt, W A; Lee, J

1983-03-01

The effects of hypophysectomy on the acquisition of conditioned taste aversions following injection of lithium chloride and following exposure to ionizing radiation were studied using a two-bottle preference test. Hypophysectomy did not disrupt the acquisition of a taste aversion following either treatment. The results are interpreted as: (a) suggesting that pituitary/adrenal hormones do not mediate the acquisition of a conditioned taste aversion following injections of lithium chloride or following exposure to ionizing radiation in a two-bottle preference test, and (b) consistent with other research suggesting that the involvement of pituitary/adrenal hormones in taste aversion learning may be related to the conflict induced by using a one-bottle test and not to the learning itself.

Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions.

PubMed

Rabin, B M; Hunt, W A

1983-04-01

A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.

Neurocognitive Development of Risk Aversion from Early Childhood to Adulthood

PubMed Central

Paulsen, David J.; Carter, R. McKell; Platt, Michael L.; Huettel, Scott A.; Brannon, Elizabeth M.

2012-01-01

Human adults tend to avoid risk. In behavioral economic studies, risk aversion is manifest as a preference for sure gains over uncertain gains. However, children tend to be less averse to risk than adults. Given that many of the brain regions supporting decision-making under risk do not reach maturity until late adolescence or beyond it is possible that mature risk-averse behavior may emerge from the development of decision-making circuitry. To explore this hypothesis, we tested 5- to 8-year-old children, 14- to 16-year-old adolescents, and young adults in a risky-decision task during functional magnetic resonance imaging (fMRI) data acquisition. To our knowledge, this is the youngest sample of children in an fMRI decision-making task. We found a number of decision-related brain regions to increase in activation with age during decision-making, including areas associated with contextual memory retrieval and the incorporation of prior outcomes into the current decision-making strategy, e.g., insula, hippocampus, and amygdala. Further, children who were more risk-averse showed increased activation during decision-making in ventromedial prefrontal cortex and ventral striatum. Our findings indicate that the emergence of adult levels of risk aversion co-occurs with the recruitment of regions supporting decision-making under risk, including the integration of prior outcomes into current decision-making behavior. This pattern of results suggests that individual differences in the development of risk aversion may reflect differences in the maturation of these neural processes. PMID:22291627

Neurocognitive development of risk aversion from early childhood to adulthood.

PubMed

Paulsen, David J; Carter, R McKell; Platt, Michael L; Huettel, Scott A; Brannon, Elizabeth M

2011-01-01

Human adults tend to avoid risk. In behavioral economic studies, risk aversion is manifest as a preference for sure gains over uncertain gains. However, children tend to be less averse to risk than adults. Given that many of the brain regions supporting decision-making under risk do not reach maturity until late adolescence or beyond it is possible that mature risk-averse behavior may emerge from the development of decision-making circuitry. To explore this hypothesis, we tested 5- to 8-year-old children, 14- to 16-year-old adolescents, and young adults in a risky-decision task during functional magnetic resonance imaging (fMRI) data acquisition. To our knowledge, this is the youngest sample of children in an fMRI decision-making task. We found a number of decision-related brain regions to increase in activation with age during decision-making, including areas associated with contextual memory retrieval and the incorporation of prior outcomes into the current decision-making strategy, e.g., insula, hippocampus, and amygdala. Further, children who were more risk-averse showed increased activation during decision-making in ventromedial prefrontal cortex and ventral striatum. Our findings indicate that the emergence of adult levels of risk aversion co-occurs with the recruitment of regions supporting decision-making under risk, including the integration of prior outcomes into current decision-making behavior. This pattern of results suggests that individual differences in the development of risk aversion may reflect differences in the maturation of these neural processes.

A Drosophila model for alcohol reward

PubMed Central

Kaun, K.R.; Azanchi, R.; Maung, Z.; Hirsh, J.; Heberlein, U.

2014-01-01

The rewarding properties of drugs contribute to the development of abuse and addiction. Here we present a new assay to investigate the motivational properties of ethanol in the genetically tractable model, Drosophila melanogaster. Flies learn to associate cues with ethanol intoxication and, although transiently aversive, the experience leads to a long-lasting attraction for the ethanol-paired cue, implying that intoxication is rewarding. Temporally blocking transmission in dopaminergic neurons revealed that flies require activation of these neurons to express, but not develop, conditioned preference for ethanol-associated cues. Moreover, flies acquire, consolidate, and retrieve these rewarding memories using distinct sets of neurons of the mushroom body. Finally, mutations in scabrous, encoding a fibrinogen-related peptide that regulates Notch signaling, disrupt the formation of memories for ethanol reward. Our results thus establish that Drosophila can be useful in understanding the molecular, genetic and neural mechanisms underling the rewarding properties of ethanol. PMID:21499254

Turning negative memories around: Contingency versus devaluation techniques.

PubMed

Dibbets, Pauline; Lemmens, Anke; Voncken, Marisol

2018-09-01

It is assumed that fear responses can be altered by changing the contingency between a conditioned stimulus (CS) and an unconditioned stimulus (US), or by devaluing the present mental representation of the US. The aim of the present study was to compare the efficacy of contingency- and devaluation-based intervention techniques on the diminishment in - and return of fear. We hypothesized that extinction (EXT, contingency-based) would outperform devaluation-based techniques regarding contingency measures, but that devaluation-based techniques would be most effective in reducing the mental representation of the US. Additionally, we expected that incorporations of the US during devaluation would result in less reinstatement of the US averseness. Healthy participants received a fear conditioning paradigm followed by one of three interventions: extinction (EXT, contingency-based), imagery rescripting (ImRs, devaluation-based) or eye movement desensitization and reprocessing (EMDR, devaluation-based). A reinstatement procedure and test followed the next day. EXT was indeed most successful in diminishing contingency-based US expectancies and skin conductance responses (SCRs), but all interventions were equally successful in reducing the averseness of the mental US representation. After reinstatement EXT showed lowest expectancies and SCRs; no differences were observed between the conditions concerning the mental US representation. A partial reinforcement schedule was used, resulting in a vast amount of contingency unaware participants. Additionally, a non-clinical sample was used, which may limit the generalizability to clinical populations. EXT is most effective in reducing conditioned fear responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

A test of the opponent-process theory of motivation using lesions that selectively block morphine reward.

PubMed

Vargas-Perez, Hector; Ting-A-Kee, Ryan A; Heinmiller, Andrew; Sturgess, Jessica E; van der Kooy, Derek

2007-06-01

The opponent-process theory of motivation postulates that motivational stimuli activate a rewarding process that is followed by an opposed aversive process in a homeostatic control mechanism. Thus, an acute injection of morphine in nondependent animals should evoke an acute rewarding response, followed by a later aversive response. Indeed, the tegmental pedunculopontine nucleus (TPP) mediates the rewarding effects of opiates in previously morphine-naive animals, but not other unconditioned effects of opiates, or learning ability. The aversive opponent process for acute morphine reward was revealed using a place-conditioning paradigm. The conditioned place aversion induced by 16-h spontaneous morphine withdrawal from an acute morphine injection in nondependent rats was abolished by TPP lesions performed prior to drug experience. However, TPP-lesioned rats did show conditioned aversions for an environment paired with the acute administration of the opioid antagonist naloxone, which blocks endogenous opioids. The results show that blocking the rewarding effects of morphine with TPP lesions also blocked the opponent aversive effects of acute morphine withdrawal in nondependent animals. Thus, this spontaneous withdrawal aversion (the opponent process) is induced by the acute rewarding effects of morphine and not by other unconditioned effects of morphine, the pharmacological effects of morphine or endogenous opioids being displaced from opiate receptors.

Interpersonal Attraction Under Negative Conditions: A Problem for the Classical Conditioning Paradigm?

ERIC Educational Resources Information Center

Kenrick, Douglas T.; Johnson, Gregory A.

The influence of aversive conditions on interpersonal attraction was investigated using 60 female undergraduates as subjects. Dyads were formed and equally divided into aversive (loud-noise) and neutral (low-noise) conditions. After completing an attitude survey questionnaire subjects completed a short filler task while the experimenter…

Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning.

PubMed

Cambon, K; Venero, C; Berezin, V; Bock, E; Sandi, C

2003-01-01

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences.

Genotypic Influence on Aversive Conditioning in Honeybees, Using a Novel Thermal Reinforcement Procedure

PubMed Central

Junca, Pierre; Carcaud, Julie; Moulin, Sibyle; Garnery, Lionel; Sandoz, Jean-Christophe

2014-01-01

In Pavlovian conditioning, animals learn to associate initially neutral stimuli with positive or negative outcomes, leading to appetitive and aversive learning respectively. The honeybee (Apis mellifera) is a prominent invertebrate model for studying both versions of olfactory learning and for unraveling the influence of genotype. As a queen bee mates with about 15 males, her worker offspring belong to as many, genetically-different patrilines. While the genetic dependency of appetitive learning is well established in bees, it is not the case for aversive learning, as a robust protocol was only developed recently. In the original conditioning of the sting extension response (SER), bees learn to associate an odor (conditioned stimulus - CS) with an electric shock (unconditioned stimulus - US). This US is however not a natural stimulus for bees, which may represent a potential caveat for dissecting the genetics underlying aversive learning. We thus first tested heat as a potential new US for SER conditioning. We show that thermal stimulation of several sensory structures on the bee’s body triggers the SER, in a temperature-dependent manner. Moreover, heat applied to the antennae, mouthparts or legs is an efficient US for SER conditioning. Then, using microsatellite analysis, we analyzed heat sensitivity and aversive learning performances in ten worker patrilines issued from a naturally inseminated queen. We demonstrate a strong influence of genotype on aversive learning, possibly indicating the existence of a genetic determinism of this capacity. Such determinism could be instrumental for efficient task partitioning within the hive. PMID:24828422

Anticipation of electric shocks modulates low beta power and event-related fields during memory encoding.

PubMed

Bauch, Eva M; Bunzeck, Nico

2015-09-01

In humans, the temporal and oscillatory dynamics of pain anticipation and its effects on long-term memory are largely unknown. Here, we investigated this open question by using a previously established behavioral paradigm in combination with magnetoencephalography (MEG). Healthy human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5 or 0.8). After encoding, memory for the studied images was tested using a remember/know recognition task. Behaviorally, pain anticipation did not modulate recollection-based recognition memory per se, but interacted with the perceived unpleasantness of the electric shock [visual analogue scale rating from 1 (not unpleasant) to 10 (highly unpleasant)]. More precisely, the relationship between pain anticipation and recollection followed an inverted u-shaped function the more unpleasant the shocks were rated by a subject. At the physiological level, this quadratic effect was mimicked in the event-related magnetic fields associated with successful memory formation ('DM-effect') ∼450ms after image onset at left frontal sensors. Importantly, across all subjects, shock anticipation modulated oscillatory power in the low beta frequency range (13-20Hz) in a linear fashion at left temporal sensors. Taken together, our findings indicate that beta oscillations provide a generic mechanism underlying pain anticipation; the effect on subsequent long-term memory, on the other hand, is much more variable and depends on the level of individual pain perception. As such, our findings give new and important insights into how aversive motivational states can drive memory formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.

PubMed

Rabin, B M; Hunt, W A

1992-09-01

The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.

Neuropsychological basic deficits in preschoolers at risk for ADHD: a meta-analysis.

PubMed

Pauli-Pott, Ursula; Becker, Katja

2011-06-01

Widely accepted neuropsychological theories on attention deficit hyperactivity disorder (ADHD) assume that the complex symptoms of the disease arise from developmentally preceding neuropsychological basic deficits. These deficits in executive functions and delay aversion are presumed to emerge in the preschool period. The corresponding normative developmental processes include phases of relative stability and rapid change. These non-linear developmental processes might have implications for concurrent and predictive associations between basic deficits and ADHD symptoms. To derive a description of the nature and strength of these associations, a meta-analysis was conducted. It is assumed that weighted mean effect sizes differ between basic deficits and depend on age. The meta-analysis included 25 articles (n=3005 children) in which associations between assessments of basic deficits (i.e. response inhibition, interference control, delay aversion, working memory, flexibility, and vigilance/arousal) in the preschool period and concurrent or subsequent ADHD symptoms or diagnosis of ADHD had been analyzed. For response inhibition and delay aversion, mean effect sizes were of medium to large magnitude while the mean effect size for working memory was small. Meta-regression analyses revealed that effect sizes of delay aversion tasks significantly decreased with increasing age while effect sizes of interference control tasks and Continuous Performance Tests (CPTs) significantly increased. Depending on the normative maturational course of each skill, time windows might exist that allow for a more or less valid assessment of a specific deficit. In future research these time windows might help to describe early developing forms of ADHD and to identify children at risk. Copyright © 2011 Elsevier Ltd. All rights reserved.

The role of eye fixation in memory enhancement under stress - An eye tracking study.

PubMed

Herten, Nadja; Otto, Tobias; Wolf, Oliver T

2017-04-01

In a stressful situation, attention is shifted to potentially relevant stimuli. Recent studies from our laboratory revealed that participants stressed perform superior in a recognition task involving objects of the stressful episode. In order to characterize the role of a stress induced alteration in visual exploration, the present study investigated whether participants experiencing a laboratory social stress situation differ in their fixation from participants of a control group. Further, we aimed at shedding light on the relation of fixation behaviour with obtained memory measures. We randomly assigned 32 male and 31 female participants to a control or a stress condition consisting of the Trier Social Stress Test (TSST), a public speaking paradigm causing social evaluative threat. In an established 'friendly' control condition (f-TSST) participants talk to a friendly committee. During both conditions, the committee members used ten office items (central objects) while another ten objects were present without being used (peripheral objects). Participants wore eye tracking glasses recording their fixations. On the next day, participants performed free recall and recognition tasks involving the objects present the day before. Stressed participants showed enhanced memory for central objects, accompanied by longer fixation times and larger fixation amounts on these objects. Contrasting this, fixation towards the committee faces showed the reversed pattern; here, control participants exhibited longer fixations. Fixation indices and memory measures were, however, not correlated with each other. Psychosocial stress is associated with altered fixation behaviour. Longer fixation on objects related to the stressful situation may reflect enhanced encoding, whereas diminished face fixation suggests gaze avoidance of aversive, socially threatening stimuli. Modified visual exploration should be considered in future stress research, in particular when focussing on memory for a stressful episode. Copyright © 2017 Elsevier Inc. All rights reserved.

Olfactory modulation by dopamine in the context of aversive learning

PubMed Central

Riffell, Jeffrey A.; Martin, Joshua P.; Gage, Stephanie L.; Nighorn, Alan J.

2012-01-01

The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing. PMID:22552185

Aging process alters hippocampal and cortical secretase activities of Wistar rats.

PubMed

Bertoldi, Karine; Cechinel, Laura Reck; Schallenberger, Bruna; Meireles, Louisiana; Basso, Carla; Lovatel, Gisele Agustini; Bernardi, Lisiane; Lamers, Marcelo Lazzaron; Siqueira, Ionara Rodrigues

2017-01-15

A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging. Copyright © 2016 Elsevier B.V. All rights reserved.

Anxiety promotes memory for mood-congruent faces but does not alter loss aversion

PubMed Central

Charpentier, Caroline J.; Hindocha, Chandni; Roiser, Jonathan P.; Robinson, Oliver J.

2016-01-01

Pathological anxiety is associated with disrupted cognitive processing, including working memory and decision-making. In healthy individuals, experimentally-induced state anxiety or high trait anxiety often results in the deployment of adaptive harm-avoidant behaviours. However, how these processes affect cognition is largely unknown. To investigate this question, we implemented a translational within-subjects anxiety induction, threat of shock, in healthy participants reporting a wide range of trait anxiety scores. Participants completed a gambling task, embedded within an emotional working memory task, with some blocks under unpredictable threat and others safe from shock. Relative to the safe condition, threat of shock improved recall of threat-congruent (fearful) face location, especially in highly trait anxious participants. This suggests that threat boosts working memory for mood-congruent stimuli in vulnerable individuals, mirroring memory biases in clinical anxiety. By contrast, Bayesian analysis indicated that gambling decisions were better explained by models that did not include threat or treat anxiety, suggesting that: (i) higher-level executive functions are robust to these anxiety manipulations; and (ii) decreased risk-taking may be specific to pathological anxiety. These findings provide insight into the complex interactions between trait anxiety, acute state anxiety and cognition, and may help understand the cognitive mechanisms underlying adaptive anxiety. PMID:27098489

Anxiety promotes memory for mood-congruent faces but does not alter loss aversion.

PubMed

Charpentier, Caroline J; Hindocha, Chandni; Roiser, Jonathan P; Robinson, Oliver J

2016-04-21

Pathological anxiety is associated with disrupted cognitive processing, including working memory and decision-making. In healthy individuals, experimentally-induced state anxiety or high trait anxiety often results in the deployment of adaptive harm-avoidant behaviours. However, how these processes affect cognition is largely unknown. To investigate this question, we implemented a translational within-subjects anxiety induction, threat of shock, in healthy participants reporting a wide range of trait anxiety scores. Participants completed a gambling task, embedded within an emotional working memory task, with some blocks under unpredictable threat and others safe from shock. Relative to the safe condition, threat of shock improved recall of threat-congruent (fearful) face location, especially in highly trait anxious participants. This suggests that threat boosts working memory for mood-congruent stimuli in vulnerable individuals, mirroring memory biases in clinical anxiety. By contrast, Bayesian analysis indicated that gambling decisions were better explained by models that did not include threat or treat anxiety, suggesting that: (i) higher-level executive functions are robust to these anxiety manipulations; and (ii) decreased risk-taking may be specific to pathological anxiety. These findings provide insight into the complex interactions between trait anxiety, acute state anxiety and cognition, and may help understand the cognitive mechanisms underlying adaptive anxiety.

Framing effects under cognitive load: the role of working memory in risky decisions.

PubMed

Whitney, Paul; Rinehart, Christa A; Hinson, John M

2008-12-01

Framing effects occur in a wide range of laboratory and natural decision contexts, but the underlying processes that produce framing effects are not well understood. We explored the role of working memory (WM) in framing by manipulating WM loads during risky decisions. After starting with a hypothetical stake of money, participants were then presented a lesser amount that they could keep for certain (positive frame) or lose for certain (negative frame). They made a choice between the sure amount and a gamble in which they could either keep or lose all of the original stake. On half of the trials, the choice was made while maintaining a concurrent WM load of random letters. In both load and no-load conditions, we replicated the typical finding of risk aversion with positive frames and risk seeking with negative frames. In addition, people made fewer decisions to accept the gamble under conditions of higher cognitive load. The data are congruent with a dual-process reasoning framework in which people employ a heuristic to make satisfactory decisions with minimal effort.

Reducing involuntary memory by interfering consolidation of stressful auditory information: A pilot study.

PubMed

Tabrizi, Fara; Jansson, Billy

2016-03-01

Intrusive emotional memories were induced by aversive auditory stimuli and modulated with cognitive tasks performed post-encoding (i.e., during consolidation). A between-subjects design was used with four conditions; three consolidation-interference tasks (a visuospatial and two verbal interference tasks) and a no-task control condition. Forty-one participants listened to a soundtrack depicting traumatic scenes (e.g., police brutality, torture and rape). Immediately after listening to the soundtrack, the subjects completed a randomly assigned task for 10 min. Intrusions from the soundtrack were reported in a diary during the following seven-day period. In line with a modality-specific approach to intrusion modulation, auditory intrusions were reduced by verbal tasks compared to both a no-task and a visuospatial interference task.. The study did not control for individual differences in imagery ability which may be a feature in intrusion development. The results provide an increased understanding of how intrusive mental images can be modulated which may have implications for preventive treatment.. Copyright © 2015 Elsevier Ltd. All rights reserved.

Taste Aversions Conditioned by the Aversiveness of Insulin and Formalin: Role of CS Specificity

ERIC Educational Resources Information Center

Domjan, Michael; Levy, Carolyn J.

1977-01-01

Experimenters in the past have reported that when insulin is used as the unconditioned stimulus (US), rats will learn an aversion to a sodium chloride but not a sucrose solution, whereas with formalin as the US, they will learn an aversion to a sucrose but not a saline solution. The present experiments failed to confirm these findings. (Editor)

The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

PubMed

Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

2008-04-01

Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

Off-vertical rotation produces conditioned taste aversion and suppressed drinking in mice

NASA Technical Reports Server (NTRS)

Fox, R. A.; Lauber, A. H.; Daunton, N. G.; Phillips, M.; Diaz, L.

1984-01-01

The effects of off-vertical rotation upon the intake of tap water immediately after rotation and upon conditioned taste aversion were assessed in mice with the tilt of the rotation axis varying from 5 to 20 deg from the earth-vertical. Conditioned taste aversion occurred in all mice that were rotated, but the intake of tap water was suppressed only in mice that were rotated at 15 or 20 deg of tilt. The greater suppression of tap-water intake and the stronger conditioned aversion in the mouse as the angle of tilt was increased in this experiment are consistent with predictions from similar experiments with human subjects, where motion sickness develops more rapidly as the angle of tilt is increased. It was suggested that off-vertical rotation may be a useful procedure for insuring experimental control over vestibular stimulation in animal studies of motion sickness.

A pilot study of loss aversion for drug and non-drug commodities in cocaine users.

PubMed

Strickland, Justin C; Beckmann, Joshua S; Rush, Craig R; Stoops, William W

2017-11-01

Numerous studies in behavioral economics have demonstrated that individuals are more sensitive to the prospect of a loss than a gain (i.e., loss aversion). Although loss aversion has been well described in "healthy" populations, little research exists in individuals with substance use disorders. This gap is notable considering the prominent role that choice and decision-making play in drug use. The purpose of this pilot study was to evaluate loss aversion in active cocaine users. Current cocaine users (N=38; 42% female) participated in this within-subjects laboratory pilot study. Subjects completed a battery of tasks designed to assess loss aversion for drug and non-drug commodities under varying risk conditions. Standardized loss aversion coefficients (λ) were compared to theoretically and empirically relevant normative values (i.e., λ=2). Compared to normative loss aversion coefficient values, a precise and consistent decrease in loss aversion was observed in cocaine users (sample λ≈1). These values were observed across drug and non-drug commodities as well as under certain and risky conditions. These data represent the first systematic study of loss aversion in cocaine-using populations and provide evidence for equal sensitivity to losses and gains or loss equivalence. Futures studies should evaluate the specificity of these effects to a history of cocaine use as well as the impact of manipulations of loss aversion on drug use to determine how this phenomenon may contribute to intervention development efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

Aversive Learning and Trait Aggression Influence Retaliatory Behavior.

PubMed

Molapour, Tanaz; Lindström, Björn; Olsson, Andreas

2016-01-01

In two experiments (n = 35, n = 34), we used a modified fear-conditioning paradigm to investigate the role of aversive learning in retaliatory behavior in social context. Participants first completed an initial aversive learning phase in which the pairing of a neutral conditioned stimulus (CS; i.e., neutral face) with a naturally aversive unconditioned stimulus (US; electric shock) was learned. Then they were given an opportunity to interact (i.e., administer 0-2 shocks) with the same faces again, during a Test phase. In Experiment 2, we used the same paradigm with the addition of online trial-by-trial ratings (e.g., US expectancy and anger) to examine the role of aversive learning, anger, and the learned expectancy of receiving punishment more closely. Our results indicate that learned aversions influenced future retaliation in a social context. In both experiments, participants showed largest skin conductance responses (SCRs) to the faces paired with one or two shocks, demonstrating successful aversive learning. Importantly, participants administered more shocks to the faces paired with the most number of shocks when the opportunity was given during test. Also, our results revealed that aggressive traits (Buss and Perry Aggression scale) were associated with retaliation only toward CSs associated with aversive experiences. These two experiments show that aggressive traits, when paired with aversive learning experiences enhance the likelihood to act anti-socially toward others.

The ontogeny of ethanol aversion.

PubMed

Saalfield, Jessica; Spear, Linda

2016-03-15

Recent work has suggested separate developmental periods within the broader framework of adolescence, with data suggesting distinct alterations and vulnerabilities within these intervals. While previous research has suggested reduced sensitivity to the aversive effects of alcohol in adolescence relative to adults, a more detailed ontogeny of this effect has yet to be conducted. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion. The current study aimed to determine the ontogeny of ethanol aversion by utilizing a conditioned taste aversion procedure at six different ages to test the hypothesis that the transitions into, through, and out of adolescence are associated with ontogenetic alterations in sensitivity to the aversive properties of ethanol. Non-deprived animals given Boost® as the conditioned stimulus (CS) were used in Experiment 1, whereas Experiment 2 used water-restricted animals provided with a saccharin/sucrose solution as the CS. In both experiments, an attenuated sensitivity to the aversive properties of ethanol was evident in adolescents compared to adults, although more age differences were apparent in water deprived animals than when a highly palatable CS was given to ad libitum animals. Overall, the data suggest an attenuated sensitivity to the aversive properties of ethanol that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. Copyright © 2016 Elsevier Inc. All rights reserved.

Aversive Learning and Trait Aggression Influence Retaliatory Behavior

PubMed Central

Molapour, Tanaz; Lindström, Björn; Olsson, Andreas

2016-01-01

In two experiments (n = 35, n = 34), we used a modified fear-conditioning paradigm to investigate the role of aversive learning in retaliatory behavior in social context. Participants first completed an initial aversive learning phase in which the pairing of a neutral conditioned stimulus (CS; i.e., neutral face) with a naturally aversive unconditioned stimulus (US; electric shock) was learned. Then they were given an opportunity to interact (i.e., administer 0–2 shocks) with the same faces again, during a Test phase. In Experiment 2, we used the same paradigm with the addition of online trial-by-trial ratings (e.g., US expectancy and anger) to examine the role of aversive learning, anger, and the learned expectancy of receiving punishment more closely. Our results indicate that learned aversions influenced future retaliation in a social context. In both experiments, participants showed largest skin conductance responses (SCRs) to the faces paired with one or two shocks, demonstrating successful aversive learning. Importantly, participants administered more shocks to the faces paired with the most number of shocks when the opportunity was given during test. Also, our results revealed that aggressive traits (Buss and Perry Aggression scale) were associated with retaliation only toward CSs associated with aversive experiences. These two experiments show that aggressive traits, when paired with aversive learning experiences enhance the likelihood to act anti-socially toward others. PMID:27375520

Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Mckenna, Susan

1991-01-01

The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

TRANSFER OF AVERSIVE RESPONDENT ELICITATION IN ACCORDANCE WITH EQUIVALENCE RELATIONS

PubMed Central

Valverde, Miguel RodrÍguez; Luciano, Carmen; Barnes-Holmes, Dermot

2009-01-01

The present study investigates the transfer of aversively conditioned respondent elicitation through equivalence classes, using skin conductance as the measure of conditioning. The first experiment is an attempt to replicate Experiment 1 in Dougher, Augustson, Markham, Greenway, and Wulfert (1994), with different temporal parameters in the aversive conditioning procedure employed. Match-to-sample procedures were used to teach 17 participants two 4-member equivalence classes. Then, one member of one class was paired with electric shock and one member of the other class was presented without shock. The remaining stimuli from each class were presented in transfer tests. Unlike the findings in the original study, transfer of conditioning was not achieved. In Experiment 2, similar procedures were used with 30 participants, although several modifications were introduced (formation of five-member classes, direct conditioning with several elements of each class, random sequences of stimulus presentation in transfer tests, reversal in aversive conditioning contingencies). More than 80% of participants who had shown differential conditioning also showed the transfer of function effect. Moreover, this effect was replicated within subjects for 3 participants. This is the first demonstration of the transfer of aversive respondent elicitation through stimulus equivalence classes with the presentation of transfer test trials in random order. The latter prevents the possibility that transfer effects are an artefact of transfer test presentation order. PMID:20119523

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats

PubMed Central

Sherrill, Luke K.; Berthold, Claire; Koss, Wendy A.; Juraska, Janice M.; Gulley, Joshua M.

2011-01-01

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol s aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0 g/kg ethanol in a binge-like pattern during postnatal days (PD) 35–45. In adulthood (> PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5 g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. PMID:21767576

Ventral, but not dorsal, hippocampus inactivation impairs reward memory expression and retrieval in contexts defined by proximal cues.

PubMed

Riaz, Sadia; Schumacher, Anett; Sivagurunathan, Seyon; Van Der Meer, Matthijs; Ito, Rutsuko

2017-07-01

The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well-established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal-based contextual memory processing in appetitively motivated tasks. Thus, the present study sought to investigate the individual roles of the dHPC and the vHPC in contextual biconditional discrimination (CBD) performance and memory retrieval. To this end, we examined the effects of transient post-acquisition pharmacological inactivation (using a combination of GABA A and GABA B receptor agonists muscimol and baclofen) of functionally distinct subregions of the HPC (CA1/CA3 subfields of the dHPC and vHPC) on CBD memory retrieval. Additional behavioral assays including novelty preference, light-dark box and locomotor activity test were also performed to confirm that the respective sites of inactivation were functionally silent. We observed robust deficits in CBD performance and memory retrieval following inactivation of the vHPC, but not the dHPC. Our data provides novel insight into the differential roles of the ventral and dorsal HPC in reward contextual processing, under conditions in which the context is defined by proximal cues. © 2017 Wiley Periodicals, Inc.

Stress and aversive learning in a wild vertebrate: the role of corticosterone in mediating escape from a novel stressor.

PubMed

Thaker, Maria; Vanak, Abi T; Lima, Steven L; Hews, Diana K

2010-01-01

Elevated plasma corticosterone during stressful events is linked to rapid changes in behavior in vertebrates and can mediate learning and memory consolidation. We tested the importance of acute corticosterone elevation in aversive learning of a novel stressor by wild male eastern fence lizards (Sceloporus undulatus). We found that inhibiting corticosterone elevation (using metyrapone, a corticosterone synthesis blocker) during an encounter with a novel attacker impaired immediate escape responses and limited learning and recall during future encounters. In the wild and in outdoor enclosures, lizards whose acute corticosterone response was blocked by an earlier metyrapone injection did not alter their escape behavior during repeated encounters with the attacker. Control-injected (unblocked) lizards, however, progressively increased flight initiation distance and decreased hiding duration during subsequent encounters. Aversive responses were also initially higher for control lizards exposed to a higher intensity first attack. Further, we demonstrate a role of corticosterone elevation in recollection, since unblocked lizards had heightened antipredator responses 24-28 h later. Exogenously restoring corticosterone levels in metyrapone-injected lizards maintained aversive behaviors and learning at control (unblocked) levels. We suggest that the corticosterone mediation of antipredator behaviors and aversive learning is a critical and general mechanism for the behavioral flexibility of vertebrate prey.

PI3-kinase cascade has a differential role in acquisition and extinction of conditioned fear memory in juvenile and adult rats.

PubMed

Slouzkey, Ilana; Maroun, Mouna

2016-12-01

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory. Our results show that Akt phosphorylation is increased following acquisition of contextual fear learning in the BLA but not in the mPFC in adult and juvenile rats. Extinction learning was not associated with changes in Akt phosphorylation. Although there were no differences in the pattern of phosphorylation of Akt either in adult or juvenile rats, microinjection of the PI3K inhibitor, LY294002, into the BLA or mPFC elicited differential effects on fear memory acquisition and extinction, depending on the site and timing of the microinjection, as well as on the age of the animal. These results suggest that PI3K/Akt has a differential role in formation, retrieval, and extinction of contextual fear memory in juvenile and adult animals, and point to developmental differences between adult and juvenile rats in mechanisms of extinction. © 2016 Slouzkey and Maroun; Published by Cold Spring Harbor Laboratory Press.

Interaction of threat and verbal working memory in adolescents.

PubMed

Patel, Nilam; Vytal, Katherine; Pavletic, Nevia; Stoodley, Catherine; Pine, Daniel S; Grillon, Christian; Ernst, Monique

2016-04-01

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety-potentiated startle). The present work examines such threat-cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n-back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety-potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Low body temperature, time dilation, and long-trace conditioned flavor aversion in rats.

PubMed

Misanin, James R; Anderson, Matthew J; Christianson, John P; Collins, Michele M; Goodhart, Mark G; Rushanan, Scott G; Hinderliter, Charles F

2002-07-01

Conditioned flavor aversion was examined in Wistar-derived albino rats that were immersed in cold water for 0, 2.5, 5, or 10 min immediately following 10-min exposure to a.1% saccharin solution and given an intraperitoneal (i.p.) injection of 0.15 M lithium chloride (LiCl) either 90, 135, 180, or 225 min later. Cold water immersion for 2.5, 5, and 10 min led to body temperature decreases of approximately 4.5, 7, and 10 degrees C, respectively. Rats whose body temperatures were not reduced (0 min immersion) showed no saccharin aversion when the LiCl was delayed 90 min. Rats whose body temperatures were reduced 4.5, 7, and 10 degrees C displayed conditioned aversions at LiCl delays up to 135, 180, and 225 min, respectively. These results were interpreted in terms of a cold-induced slowing of a biochemical clock that may uniquely govern specific timing processes involved in associative learning over long delays, such as long-trace conditioned flavor aversion, learned safety, and certain types of learning that involve an extensive time lapse (e.g., extinction of fear). Copyright 2002 Elsevier Science (USA).

Distinct Contributions of Ventromedial and Dorsolateral Subregions of the Human Substantia Nigra to Appetitive and Aversive Learning

PubMed Central

Larsen, Tobias; Collette, Sven; Tyszka, Julian M.; Seymour, Ben; O'Doherty, John P.

2015-01-01

The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during appetitive learning has been well established. Less is known about the differential contribution of these midbrain regions to appetitive versus aversive learning, especially in humans. Here we scanned human participants with high-resolution fMRI focused on the SN and VTA while they participated in a sequential Pavlovian conditioning paradigm involving an appetitive outcome (a pleasant juice), as well as an aversive outcome (an unpleasant bitter and salty flavor). We found a degree of regional specialization within the SN: Whereas a region of ventromedial SN correlated with a temporal difference reward prediction error during appetitive Pavlovian learning, a dorsolateral area correlated instead with an aversive expected value signal in response to the most distal cue, and to a reward prediction error in response to the most proximal cue to the aversive outcome. Furthermore, participants' affective reactions to both the appetitive and aversive conditioned stimuli more than 1 year after the fMRI experiment was conducted correlated with activation in the ventromedial and dorsolateral SN obtained during the experiment, respectively. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts. SIGNIFICANCE STATEMENT The role of the substantia nigra (SN) and ventral tegmental area (VTA) in appetitive learning is well established, but less is known about their contribution to aversive compared with appetitive learning, especially in humans. We used high-resolution fMRI to measure activity in the SN and VTA while participants underwent higher-order Pavlovian learning. We found a regional specialization within the SN: a ventromedial area was selectively engaged during appetitive learning, and a dorsolateral area during aversive learning. Activity in these areas predicted affective reactions to appetitive and aversive conditioned stimuli over 1 year later. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts. PMID:26490862

"Incidental fear cues increase monetary loss aversion": Correction to Schulreich, Gerhardt, and Heekeren (2016).

PubMed

2016-12-01

Reports an error in "Incidental fear cues increase monetary loss aversion" by Stefan Schulreich, Holger Gerhardt and Hauke R. Heekeren ( Emotion , 2016[Apr], Vol 16[3], 402-412). In the current article, there was an error in the Study 2 portion of the article. The fourth paragraph of the Results section should read as follows: Performing the same analyses as in Study 1, we found an effect of incidental fear cues on decision behavior. Participants accepted fewer gambles in the fearful-face condition (32.77%) than in the neutral-face condition (33.96%), with Z = -2.187, p = .027, d = -0.998 in the Wilcoxon signed-ranks test and β = 0.012, SE = 0.0053, F(1, 21) = 4.434, p = .047, partial η² = .174 in the linear regression. This suggests increased risk aversion in the fearful-face condition. Concerning personality, however, there were no significant between-subjects effects or between-within interaction effects (all ps = .349). (The following abstract of the original article appeared in record 2015-52358-001.) In many everyday decisions, people exhibit loss aversion-a greater sensitivity to losses relative to gains of equal size. Loss aversion is thought to be (at least partly) mediated by emotional-in particular, fear-related-processes. Decision research has shown that even incidental emotions, which are unrelated to the decision at hand, can influence decision making. The effect of incidental fear on loss aversion, however, is thus far unclear. In two studies, we experimentally investigated how incidental fear cues, presented during (Study 1) or before (Study 2) choices to accept or reject mixed gambles over real monetary stakes, influence monetary loss aversion. We find that the presentation of fearful faces, relative to the presentation of neutral faces, increased risk aversion-an effect that could be attributed to increased loss aversion. The size of this effect was moderated by psychopathic personality: Fearless dominance, in particular its interpersonal facet, but not self-centered impulsivity, attenuated the effect of incidental fear cues on loss aversion, consistent with reduced fear reactivity. Together, these results highlight the sensitivity of loss aversion to the affective context. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Conditioning and aversion to toxic Solanum bonariense (naranjillo) leaves in calves

USDA-ARS?s Scientific Manuscript database

Solanum bonariense is a perennial poisonous shrub that induces cerebellar cortical degeneration when eaten by cattle. The aim of this research was to outline a protocol to induce a conditioned aversion to this plant. During the pre-conditioning period ten calves (126±12kg BW) were maintained at half...

ABA, AAB and ABC Renewal in Taste Aversion Learning

ERIC Educational Resources Information Center

Bernal-Gamboa, Rodolfo; Juarez, Yectivani; Gonzalez-Martin, Gabriela; Carranza, Rodrigo; Sanchez-Carrasco, Livia; Nieto, Javier

2012-01-01

Context renewal is identified when the conditioned response (CR) elicited by an extinguished conditioned stimulus (CS) reappears as a result of changing the contextual cues during the test. Two experiments were designed for testing contextual renewal in a conditioned taste aversion preparation. Experiment 1 assessed ABA and AAB context renewal,…

A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories

PubMed Central

Agis-Balboa, Roberto Carlos; Arcos-Diaz, Dario; Wittnam, Jessica; Govindarajan, Nambirajan; Blom, Kim; Burkhardt, Susanne; Haladyniak, Ulla; Agbemenyah, Hope Yao; Zovoilis, Athanasios; Salinas-Riester, Gabriella; Opitz, Lennart; Sananbenesi, Farahnaz; Fischer, Andre

2011-01-01

Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example, the expression of an aversive behaviour upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinction are only beginning to emerge. Here, we show that fear extinction initiates upregulation of hippocampal insulin-growth factor 2 (Igf2) and downregulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation, we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2 signalling during fear extinction. To this end, we show that fear extinction-induced IGF2/IGFBP7 signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. In conclusion, our data suggest that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. PMID:21873981

Elevated Responding to Safe Conditions as a Specific Risk Factor for Anxiety Versus Depressive Disorders: Evidence From a Longitudinal Investigation

PubMed Central

Craske, Michelle G.; Wolitzky–Taylor, Kate B.; Mineka, Susan; Zinbarg, Richard; Waters, Allison M.; Vrshek–Schallhorn, Suzanne; Epstein, Alyssa; Naliboff, Bruce; Ornitz, Edward

2013-01-01

The current study evaluated the degree to which startle reflexes (SRs) in safe conditions versus danger conditions were predictive of the onset of anxiety disorders. Specificity of these effects to anxiety disorders was evaluated in comparison to unipolar depressive disorders and with consideration of level of neuroticism. A startle paradigm was administered at baseline to 132 nondisordered adolescents as part of a longitudinal study examining risk factors for emotional disorders. Participants underwent a repetition of eight safe-danger sequences and were told that delivery of an aversive stimulus leading to a muscle contraction of the arm would occur only in the late part of danger conditions. One aversive stimulus occurred midway in the safe-danger sequences. Participants were assessed for the onset of anxiety and unipolar depressive disorders annually over the next 3 to 4 years. Larger SR magnitude during safe conditions following delivery of the aversive stimulus predicted the subsequent first onset of anxiety disorders. Moreover, prediction of the onset of anxiety disorders remained significant above and beyond the effects of comorbid unipolar depression, neuroticism, and subjective ratings of intensity of the aversive stimulus. In sum, elevated responding to safe conditions following an aversive stimulus appears to be a specific, prospective risk factor for the first onset of anxiety disorders. PMID:21988452

Chronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons.

PubMed

Barik, Jacques; Marti, Fabio; Morel, Carole; Fernandez, Sebastian P; Lanteri, Christophe; Godeheu, Gérard; Tassin, Jean-Pol; Mombereau, Cédric; Faure, Philippe; Tronche, François

2013-01-18

Repeated traumatic events induce long-lasting behavioral changes that are key to organism adaptation and that affect cognitive, emotional, and social behaviors. Rodents subjected to repeated instances of aggression develop enduring social aversion and increased anxiety. Such repeated aggressions trigger a stress response, resulting in glucocorticoid release and activation of the ascending dopamine (DA) system. We bred mice with selective inactivation of the gene encoding the glucocorticoid receptor (GR) along the DA pathway, and exposed them to repeated aggressions. GR in dopaminoceptive but not DA-releasing neurons specifically promoted social aversion as well as dopaminergic neurochemical and electrophysiological neuroadaptations. Anxiety and fear memories remained unaffected. Acute inhibition of the activity of DA-releasing neurons fully restored social interaction in socially defeated wild-type mice. Our data suggest a GR-dependent neuronal dichotomy for the regulation of emotional and social behaviors, and clearly implicate GR as a link between stress resiliency and dopaminergic tone.

A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models.

PubMed

Coghill, D R; Seth, S; Matthews, K

2014-07-01

Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning. The neuropsychological functioning of 83 medication-naive boys with well-characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks. Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)]. The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment.

Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.

PubMed

Anderson, R I; Agoglia, A E; Morales, M; Varlinskaya, E I; Spear, L P

2013-09-26

Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by nor-binaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Advantageous Inequity Aversion Does Not Always Exist: The Role of Determining Allocations Modulates Preferences for Advantageous Inequity.

PubMed

Li, Ou; Xu, Fuming; Wang, Lei

2018-01-01

Previous studies have shown that people would like to sacrifice benefits to themselves in order to avoid inequitable outcomes, not only when they receive less than others (disadvantageous inequity aversion) but also when they receive more (advantageous inequity aversion). This feature is captured by the theory of inequity aversion. The present study was inspired by what appears to be asymmetry in the research paradigm toward advantageous inequity aversion. Specifically, studies that supported the existence of advantageous inequity aversion always relied on the paradigm in which participants can determine allocations. Thus, it is interesting to know what would occur if participants could not determine allocations or simply passed judgment on predetermined allocations. To address this, a behavioral experiment ( N = 118) and a skin conductance response (SCR) experiment ( N = 29) were adopted to compare participants' preferences for advantageous inequity directly when allocations were determined and when allocations were predetermined in an allocating task. In the determined condition, participants could divide by themselves a sum of money between themselves and a matched person, whereas in the predetermined condition, they could simply indicate their satisfaction with an equivalent program-generated allocation. It was found that, compared with those in the determined condition, participants in the predetermined condition behaved as if they liked the advantageous inequity and equity to the same degree (Experiment One) and that the SCRs elicited by advantageous inequity had no differences from those elicited by equity, suggesting that participants did not feel negatively toward advantageous inequity in this situation (Experiment Two). The present study provided mutual corroboration (behavioral and electrophysiological data) to document that advantageous inequity aversion may differ as a function of the individual's role in determining allocations, and it would disappear if individual cannot determine allocations.

Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

PubMed

Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

2006-04-01

Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

PubMed

Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

2011-11-20

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.

Appetitive but not aversive olfactory conditioning modifies antennal movements in honeybees

PubMed Central

Cholé, Hanna; Junca, Pierre

2015-01-01

In honeybees, two olfactory conditioning protocols allow the study of appetitive and aversive Pavlovian associations. Appetitive conditioning of the proboscis extension response (PER) involves associating an odor, the conditioned stimulus (CS) with a sucrose solution, the unconditioned stimulus (US). Conversely, aversive conditioning of the sting extension response (SER) involves associating the odor CS with an electric or thermal shock US. Each protocol is based on the measure of a different behavioral response (proboscis versus sting) and both only provide binary responses (extension or not of the proboscis or sting). These limitations render the measure of the acquired valence of an odor CS difficult without testing the animals in a freely moving situation. Here, we studied the effects of both olfactory conditioning protocols on the movements of the antennae, which are crucial sensory organs for bees. As bees’ antennae are highly mobile, we asked whether their movements in response to an odorant change following appetitive or aversive conditioning and if so, do odor-evoked antennal movements contain information about the acquired valence of the CS? We implemented a tracking system for harnessed bees’ antennal movements based on a motion capture principle at a high frequency rate. We observed that differential appetitive conditioning had a strong effect on antennal movements. Bees responded to the reinforced odorant with a marked forward motion of the antennae and a strong velocity increase. Conversely, differential aversive conditioning had no associative effect on antennal movements. Rather than revealing the acquired valence of an odorant, antennal movements may represent a novel conditioned response taking place during appetitive conditioning and may provide a possible advantage to bees when foraging in natural situations. PMID:26572651

Neurobiology of anxiety disorders and implications for treatment.

PubMed

Garakani, Amir; Mathew, Sanjay J; Charney, Dennis S

2006-11-01

The neurobiology of the anxiety disorders, which include panic disorder, post-traumatic stress disorder (PTSD), and specific phobias, among others, has been clarified by advances in the field of classical or Pavlovian conditioning, and in our understanding of basic mechanisms of memory and learning. Fear conditioning occurs when a neutral conditioned stimulus (such as a tone) is paired with an aversive, or unconditioned stimulus (such as a footshock), and then in the absence of the unconditioned stimulus, causes a conditioned fear response. Preclinical studies have shown that the amygdala plays a key role in fear circuitry, and that abnormalities in amygdala pathways can affect the acquisition and expression of fear conditioning. Drugs such as glutamate N-methyl-D-aspartate (NMDA) antagonists, and blockers of voltage-gated calcium channels, in the amygdala, may block these effects. There is also preliminary evidence for the use of centrally acting beta-adrenergic antagonists, like propranolol, to inhibit consolidation of traumatic memories in PTSD. Finally, fear extinction, which entails new learning of fear inhibition, is central to the mechanism of effective anti-anxiety treatments. Several pharmacological manipulations, such as D-cycloserine, a partial NMDA agonist, have been found to facilitate extinction. Combining these medication approaches with psychotherapies that promote extinction, such as cognitive behavioral therapy (CBT), may offer patients with anxiety disorders a rapid and robust treatment with good durability of effect.

Lesions of the entorhinal cortex or fornix disrupt the context-dependence of fear extinction in rats.

PubMed

Ji, Jinzhao; Maren, Stephen

2008-12-12

Recent studies have shown that the hippocampus is critical for the context-dependent expression of extinguished fear memories. Here we used Pavlovian fear conditioning in rats to explore whether the entorhinal cortex and fornix, which are the major cortical and subcortical interfaces of the hippocampus, are also involved in the context-dependence of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock (unconditional stimulus or US) in one context, rats received an extinction session in which the CS was presented without the US in another context. Conditional fear to the CS was then tested in either the extinction context or a third familiar context; freezing behavior served as the index of fear. Sham-operated rats exhibited little conditional freezing to the CS in the extinction context, but showed a robust renewal of fear when tested outside of the extinction context. In contrast, rats with neurotoxic lesions in the entorhinal cortex or electrolytic lesions in the fornix did not exhibit a renewal of fear when tested outside the extinction context. Impairments in freezing behavior to the auditory CS were not able to account for the observed results, insofar as rats with either entorhinal cortex or fornix lesions exhibited normal freezing behavior during the conditioning session. Thus, contextual memory retrieval requires not only the hippocampus proper, but also its cortical and subcortical interfaces.

Electrical Stimulation of Lateral Habenula during Learning: Frequency-Dependent Effects on Acquisition but Not Retrieval of a Two-Way Active Avoidance Response

PubMed Central

Wetzel, Wolfram; Scheich, Henning; Ohl, Frank W.

2013-01-01

The lateral habenula (LHb) is an epithalamic structure involved in signaling reward omission and aversive stimuli, and it inhibits dopaminergic neurons during motivated behavior. Less is known about LHb involvement in the acquisition and retrieval of avoidance learning. Our previous studies indicated that brief electrical stimulation of the LHb, time-locked to the avoidance of aversive footshock (presumably during the positive affective “relief” state that occurs when an aversive outcome is averted), inhibited the acquisition of avoidance learning. In the present study, we used the same paradigm to investigate different frequencies of LHb stimulation. The effect of 20 Hz vs. 50 Hz vs. 100 Hz stimulation was investigated during two phases, either during acquisition or retrieval in Mongolian gerbils. The results indicated that 50 Hz, but not 20 Hz, was sufficient to produce a long-term impairment in avoidance learning, and was somewhat more effective than 100 Hz in this regard. None of the stimulation parameters led to any effects on retrieval of avoidance learning, nor did they affect general motor activity. This suggests that, at frequencies in excess of the observed tonic firing rates of LHb neurons (>1–20 Hz), LHb stimulation may serve to interrupt the consolidation of new avoidance memories. However, these stimulation parameters are not capable of modifying avoidance memories that have already undergone extensive consolidation. PMID:23840355

Motion Sickness-Induced Food Aversions in the Squirrel Monkey

NASA Technical Reports Server (NTRS)

Roy, M. Aaron; Brizzee, Kenneth R.

1979-01-01

Conditioned aversions to colored, flavored water were established in Squirrel monkeys (Saimiri sciureus) by following consumption with 90 min of simultaneous rotational and vertical stimulation. The experimental group (N= 13) drank significantly less of the green, almond-flavored test solution than did the control group (N=14) during three post-treatment preference testing days. Individual differences were noted in that two experimental monkeys readily drank the test solution after rotational stimulation. Only two of the experimental monkeys showed emesis during rotation, yet 10 monkeys in this group developed an aversion. These results suggest that: (1) motion sickness can be readily induced in Squirrel monkeys with simultaneous rotational and vertical stimulation, and (2) that conditioned food aversions are achieved in the absence of emesis in this species.

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

PubMed Central

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes. PMID:21960964

Attraction under Aversive Conditions: Misattributions or Fear-Reduction?

ERIC Educational Resources Information Center

Miller, Rowland S.

Interpersonal attraction appears to increase under aversive conditions. Two distinct theories suggest that attraction results from either misattribution or fear reduction. To investigate the effects of misattribution and fear reduction on attraction, 36 male college students were ostensibly exposed to an electromagnetic field while an attractive…

Preventing the return of fear memories with postretrieval extinction: A human study using a burst of white noise as an aversive stimulus.

PubMed

Fernandez-Rey, Jose; Gonzalez-Gonzalez, Daniel; Redondo, Jaime

2018-06-07

Standard extinction procedures seem to imply an inhibition of the fear response, but not a modification of the original fear-memory trace, which remains intact (Bouton, 2002, 2004). Typically, the behavioral procedure used to modify this trace is the so-called postretrieval extinction, consisting of fear-memory reactivation followed by extinction applied within the reconsolidation window. However, the application of this technique yields mixed results, probably due to a series of boundary conditions that limit the effectiveness of postretrieval-extinction effects. In this study a number of potential, and hitherto unexplored, moderators of such effects are considered. Using an interval of 48 hr between extinction and re-extinction, the findings show a spontaneous recovery similar to that found in studies that use a 24-hr interval. Also, the use of intervals of 10 and 20 min between reactivation and extinction led to a similar fear return. Finally, the burst of white noise used as an unconditioned stimulus (US) here was shown to be as effective as the electric shock normally used in the study of fear-memory reconsolidation. These findings suggest that postretrieval extinction is an effective behavioral technique for modifying the original fear memory and for the elimination of the fear return. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Flavour exposures after conditioned aversion or preference trigger different brain processes in anaesthetised pigs.

PubMed

Gaultier, A; Meunier-Salaün, M C; Malbert, C H; Val-Laillet, D

2011-11-01

We describe the behavioural consequences of conditioned flavour aversion and preference in pigs and have investigated the brain circuits involved in the representation of flavours with different hedonic values. The study was performed on eight 30-kg pigs. (i) Animals were negatively conditioned to an F- flavour added to a meal followed by LiCl intraduodenal (i.d.) injection, and positively conditioned to an F+ flavour added to a meal followed by NaCl i.d. injection. F+ and F- were thyme or cinnamon flavours. After each conditioning, the behavioural activities were recorded; (ii) One and 5 weeks later, animals were subjected to three two-choice food tests to investigate their preferences between F+, F- and a novel flavour (O); and (iii) Anaesthetised animals were subjected to three SPECT brain imaging sessions: control situation (no flavour) and exposure to F+ and to F-. The negative reinforcement induced a physical malaise and visceral illness. After a positive reinforcement, animals showed playing or feeding motivation and quietness. F+ was significantly preferred over O and F-, and O was significantly preferred over F-. Both F- and F+ induced some metabolic differences in neural circuits involved in sensory associative processes, learning and memory, emotions, reward and feeding motivation. Exposure to F+ induced a higher activity in corticolimbic and reward-related areas, while F- induced a deactivation of the basal nuclei and limbic thalamic nuclei. This study reveals the unconscious cognitive dimension evoked by food flavours according to the individual experience, and highlights the importance of the food sensory image on hedonism and anticipatory eating behaviour. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Memory reconsolidation may be disrupted by a distractor stimulus presented during reactivation

PubMed Central

Crestani, Ana Paula; Zacouteguy Boos, Flávia; Haubrich, Josué; Ordoñez Sierra, Rodrigo; Santana, Fabiana; Molina, Johanna Marcela Duran; Cassini, Lindsey de Freitas; Alvares, Lucas de Oliveira; Quillfeldt, Jorge Alberto

2015-01-01

Memories can be destabilized by the reexposure to the training context, and may reconsolidate into a modified engram. Reconsolidation relies on some particular molecular mechanisms involving LVGCCs and GluN2B-containing NMDARs. In this study we investigate the interference caused by the presence of a distractor - a brief, unanticipated stimulus that impair a fear memory expression - during the reactivation session, and tested the hypothesis that this disruptive effect relies on a reconsolidation process. Rats previously trained in the contextual fear conditioning (CFC) were reactivated in the presence or absence of a distractor stimulus. In the test, groups reactivated in the original context with distractor displayed a reduction of the freezing response lasting up to 20 days. To check for the involvement of destabilization / reconsolidation mechanisms, we studied the effect of systemic nimodipine (a L-VGCC blocker) or intra-CA1 ifenprodil (a selective GluN2B/NMDAR antagonist) infused right before the reactivation session. Both treatments were able to prevent the disruptive effect of distraction. Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon. Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way. PMID:26328547

Repeatable aversion across threat types is linked with life-history traits but is dependent on how aversion is measured.

PubMed

Davidson, Gabrielle L; Reichert, Michael S; Crane, Jodie M S; O'Shea, William; Quinn, John L

2018-02-01

Personality research suggests that individual differences in risk aversion may be explained by links with life-history variation. However, few empirical studies examine whether repeatable differences in risk avoidance behaviour covary with life-history traits among individuals in natural populations, or how these links vary depending on the context and the way risk aversion is measured. We measured two different risk avoidance behaviours (latency to enter the nest and inspection time) in wild great tits ( Parus major ) in two different contexts-response to a novel object and to a predator cue placed at the nest-box during incubation---and related these behaviours to female reproductive success and condition. Females responded equally strongly to both stimuli, and although both behaviours were repeatable, they did not correlate. Latency to enter was negatively related to body condition and the number of offspring fledged. By contrast, inspection time was directly explained by whether incubating females had been flushed from the nest before the trial began. Thus, our inferences on the relationship between risk aversion and fitness depend on how risk aversion was measured. Our results highlight the limitations of drawing conclusions about the relevance of single measures of a personality trait such as risk aversion.

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase.

PubMed

Fuertig, René; Azzinnari, Damiano; Bergamini, Giorgio; Cathomas, Flurin; Sigrist, Hannes; Seifritz, Erich; Vavassori, Stefano; Luippold, Andreas; Hengerer, Bastian; Ceci, Angelo; Pryce, Christopher R

2016-05-01

Psychosocial stress is a major risk factor for mood and anxiety disorders, in which excessive reactivity to aversive events/stimuli is a major psychopathology. In terms of pathophysiology, immune-inflammation is an important candidate, including high blood and brain levels of metabolites belonging to the kynurenine pathway. Animal models are needed to study causality between psychosocial stress, immune-inflammation and hyper-reactivity to aversive stimuli. The present mouse study investigated effects of psychosocial stress as chronic social defeat (CSD) versus control-handling (CON) on: Pavlovian tone-shock fear conditioning, activation of the kynurenine pathway, and efficacy of a specific inhibitor (IDOInh) of the tryptophan-kynurenine catabolising enzyme indoleamine 2,3-dioxygenase (IDO1), in reversing CSD effects on the kynurenine pathway and fear. CSD led to excessive fear learning and memory, whilst repeated oral escitalopram (antidepressant and anxiolytic) reversed excessive fear memory, indicating predictive validity of the model. CSD led to higher blood levels of TNF-α, IFN-γ, kynurenine (KYN), 3-hydroxykynurenine (3-HK) and kynurenic acid, and higher KYN and 3-HK in amygdala and hippocampus. CSD was without effect on IDO1 gene or protein expression in spleen, ileum and liver, whilst increasing liver TDO2 gene expression. Nonetheless, oral IDOInh reduced blood and brain levels of KYN and 3-HK in CSD mice to CON levels, and we therefore infer that CSD increases IDO1 activity by increasing its post-translational activation. Furthermore, repeated oral IDOInh reversed excessive fear memory in CSD mice to CON levels. IDOInh reversal of CSD-induced hyper-activity in the kynurenine pathway and fear system contributes significantly to the evidence for a causal pathway between psychosocial stress, immune-inflammation and the excessive fearfulness that is a major psychopathology in stress-related neuropsychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Event-related potential components as measures of aversive conditioning in humans.

PubMed

Bacigalupo, Felix; Luck, Steven J

2018-04-01

For more than 60 years, the gold standard for assessing aversive conditioning in humans has been the skin conductance response (SCR), which arises from the activation of the peripheral nervous system. Although the SCR has been proven useful, it has some properties that impact the kinds of questions it can be used to answer. In particular, the SCR is slow, reaching a peak 4-5 s after stimulus onset, and it decreases in amplitude after a few trials (habituation). The present study asked whether the late positive potential (LPP) of the ERP waveform could be a useful complementary method for assessing aversive conditioning in humans. The SCR and LPP were measured in an aversive conditioning paradigm consisting of three blocks in which one color was paired with a loud noise (CS+) and other colors were not paired with the noise (CS-). Participants also reported the perceived likelihood of being exposed to the noise for each color. Both SCR and LPP were significantly larger on CS+ trials than on CS- trials. However, SCR decreased steeply after the first conditioning block, whereas LPP and self-reports were stable over blocks. These results indicate that the LPP can be used to assess aversive conditioning and has several useful properties: (a) it is a direct response of the central nervous system, (b) it is fast, with an onset latency of 300 ms, (c) it does not habituate over time. © 2017 Society for Psychophysiological Research.

Conditioning food aversions to Ipomoea carnea var. Fistulosa in sheep

USDA-ARS?s Scientific Manuscript database

Ipomoea carnea is a toxic plant in Brazil that often poisons sheep. Conditioned food aversion may be a tool to reduce intoxication problems in grazing sheep. Fifteen sheep were adapted to consume I. carnea for 36 days. Subsequently sheep were randomly divided into three groups of five sheep each. ...

Conditioned flavor aversion and location avoidance in hamsters from toxic extract of tall larkspur (Delphinium barbeyi)

USDA-ARS?s Scientific Manuscript database

Studies were conducted to address conditioned flavour aversion (CFA) and place avoidance learning in hamsters given injections of alkaloid extracts from tall larkspur (Delphinium barbeyi), to determine if larkspur had reinforcing or negative properties sufficient to cause place avoidance or preferen...

Conditioned Taste Aversion Is Enhanced When the Unconditioned Stimulus Is Presented in a Different Context

ERIC Educational Resources Information Center

Ishii, Kiyoshi; Iguchi, Yoshio; Fukumoto, Kazuya; Nakayasu, Tomohiro

2008-01-01

Using a conditioned taste aversion procedure with rats as the subjects, two experiments examined the effect of presenting a conditioned stimulus (CS saccharin solution) in one context followed by an unconditioned stimulus (US LiCl) in a different context. Experiment 1 showed that animals which received the above-mentioned procedure (Group D)…

Measurements of Chlorpyrifos Levels in Forager Bees and Comparison with Levels that Disrupt Honey Bee Odor-Mediated Learning Under Laboratory Conditions.

PubMed

Urlacher, Elodie; Monchanin, Coline; Rivière, Coraline; Richard, Freddie-Jeanne; Lombardi, Christie; Michelsen-Heath, Sue; Hageman, Kimberly J; Mercer, Alison R

2016-02-01

Chlorpyrifos is an organophosphate pesticide used around the world to protect food crops against insects and mites. Despite guidelines for chlorpyrifos usage, including precautions to protect beneficial insects, such as honeybees from spray drift, this pesticide has been detected in bees in various countries, indicating that exposure still occurs. Here, we examined chlorpyrifos levels in bees collected from 17 locations in Otago, New Zealand, and compared doses of this pesticide that cause sub-lethal effects on learning performance under laboratory conditions with amounts of chlorpyrifos detected in the bees in the field. The pesticide was detected at 17 % of the sites sampled and in 12 % of the colonies examined. Amounts detected ranged from 35 to 286 pg.bee(-1), far below the LD50 of ~100 ng.bee(-1). We detected no adverse effect of chlorpyrifos on aversive learning, but the formation and retrieval of appetitive olfactory memories was severely affected. Chlorpyrifos fed to bees in amounts several orders of magnitude lower than the LD50, and also lower than levels detected in bees, was found to slow appetitive learning and reduce the specificity of memory recall. As learning and memory play a central role in the behavioral ecology and communication of foraging bees, chlorpyrifos, even in sublethal doses, may threaten the success and survival of this important insect pollinator.

Spatio-temporal dynamics of brain mechanisms in aversive classical conditioning: high-density event-related potential and brain electrical tomography analyses.

PubMed

Pizzagalli, Diego A; Greischar, Lawrence L; Davidson, Richard J

2003-01-01

Social cognition, including complex social judgments and attitudes, is shaped by individual learning experiences, where affect often plays a critical role. Aversive classical conditioning-a form of associative learning involving a relationship between a neutral event (conditioned stimulus, CS) and an aversive event (unconditioned stimulus, US)-represents a well-controlled paradigm to study how the acquisition of socially relevant knowledge influences behavior and the brain. Unraveling the temporal unfolding of brain mechanisms involved appears critical for an initial understanding about how social cognition operates. Here, 128-channel ERPs were recorded in 50 subjects during the acquisition phase of a differential aversive classical conditioning paradigm. The CS+ (two fearful faces) were paired 50% of the time with an aversive noise (CS upward arrow + /Paired), whereas in the remaining 50% they were not (CS upward arrow + /Unpaired); the CS- (two different fearful faces) were never paired with the noise. Scalp ERP analyses revealed differences between CS upward arrow + /Unpaired and CS- as early as approximately 120 ms post-stimulus. Tomographic source localization analyses revealed early activation modulated by the CS+ in the ventral visual pathway (e.g. fusiform gyrus, approximately 120 ms), right middle frontal gyrus (approximately 176 ms), and precuneus (approximately 240 ms). At approximately 120 ms, the CS- elicited increased activation in the left insula and left middle frontal gyrus. These findings not only confirm a critical role of prefrontal, insular, and precuneus regions in aversive conditioning, but they also suggest that biologically and socially salient information modulates activation at early stages of the information processing flow, and thus furnish initial insight about how affect and social judgments operate.

Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

PubMed Central

Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

2015-01-01

Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be—in part—due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID:26191015

Ambiguity aversion and household portfolio choice puzzles: Empirical evidence*

PubMed Central

Dimmock, Stephen G.; Kouwenberg, Roy; Mitchell, Olivia S.; Peijnenburg, Kim

2017-01-01

We test the relation between ambiguity aversion and five household portfolio choice puzzles: nonparticipation in equities, low allocations to equity, home-bias, own-company stock ownership, and portfolio under-diversification. In a representative US household survey, we measure ambiguity preferences using custom-designed questions based on Ellsberg urns. As theory predicts, ambiguity aversion is negatively associated with stock market participation, the fraction of financial assets in stocks, and foreign stock ownership, but it is positively related to own-company stock ownership. Conditional on stock ownership, ambiguity aversion is related to portfolio under-diversification, and during the financial crisis, ambiguity-averse respondents were more likely to sell stocks. PMID:28458446

Ambiguity aversion and household portfolio choice puzzles: Empirical evidence.

PubMed

Dimmock, Stephen G; Kouwenberg, Roy; Mitchell, Olivia S; Peijnenburg, Kim

2016-03-01

We test the relation between ambiguity aversion and five household portfolio choice puzzles: nonparticipation in equities, low allocations to equity, home-bias, own-company stock ownership, and portfolio under-diversification. In a representative US household survey, we measure ambiguity preferences using custom-designed questions based on Ellsberg urns. As theory predicts, ambiguity aversion is negatively associated with stock market participation, the fraction of financial assets in stocks, and foreign stock ownership, but it is positively related to own-company stock ownership. Conditional on stock ownership, ambiguity aversion is related to portfolio under-diversification, and during the financial crisis, ambiguity-averse respondents were more likely to sell stocks.

Drug-induced conditioned place preference and aversion in mice.

PubMed

Cunningham, Christopher L; Gremel, Christina M; Groblewski, Peter A

2006-01-01

This protocol describes the equipment and methods used to establish conditioned place preference (CPP) or aversion (CPA). Place conditioning is a form of Pavlovian conditioning routinely used to measure the rewarding or aversive motivational effects of objects or experiences (e.g., abused drugs). Here, we present a place conditioning procedure that has been used extensively to study the motivational effects of ethanol and other abused drugs in mice. This protocol involves three phases: (i) habituation (or a pretest), (ii) conditioning of an association between the drug and a tactile or visual stimulus and (iii) a test that offers a choice between the drug-associated cue and a neutral cue. If the drug has motivational significance, mice will spend significantly more time (CPP) or less time (CPA) in proximity to the drug-associated cue. Potential problems in the design and interpretation of place conditioning studies are discussed. A typical experiment lasts 2 weeks.

Does Risk Aversion Affect Transmission and Generation Planning? A Western North America Case Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munoz, Francisco; van der Weijde, Adriaan Hendrik; Hobbs, Benjamin F.

Here, we investigate the effects of risk aversion on optimal transmission and generation expansion planning in a competitive and complete market. To do so, we formulate a stochastic model that minimizes a weighted average of expected transmission and generation costs and their conditional value at risk (CVaR). We also show that the solution of this optimization problem is equivalent to the solution of a perfectly competitive risk-averse Stackelberg equilibrium, in which a risk-averse transmission planner maximizes welfare after which risk-averse generators maximize profits. Furthermore, this model is then applied to a 240-bus representation of the Western Electricity Coordinating Council, inmore » which we examine the impact of risk aversion on levels and spatial patterns of generation and transmission investment. Although the impact of risk aversion remains small at an aggregate level, state-level impacts on generation and transmission investment can be significant, which emphasizes the importance of explicit consideration of risk aversion in planning models.« less

Does Risk Aversion Affect Transmission and Generation Planning? A Western North America Case Study

DOE PAGES

Munoz, Francisco; van der Weijde, Adriaan Hendrik; Hobbs, Benjamin F.; ...

2017-04-07

Here, we investigate the effects of risk aversion on optimal transmission and generation expansion planning in a competitive and complete market. To do so, we formulate a stochastic model that minimizes a weighted average of expected transmission and generation costs and their conditional value at risk (CVaR). We also show that the solution of this optimization problem is equivalent to the solution of a perfectly competitive risk-averse Stackelberg equilibrium, in which a risk-averse transmission planner maximizes welfare after which risk-averse generators maximize profits. Furthermore, this model is then applied to a 240-bus representation of the Western Electricity Coordinating Council, inmore » which we examine the impact of risk aversion on levels and spatial patterns of generation and transmission investment. Although the impact of risk aversion remains small at an aggregate level, state-level impacts on generation and transmission investment can be significant, which emphasizes the importance of explicit consideration of risk aversion in planning models.« less

Attenuation and cross-attenuation in taste-aversion learning in the rat: Studies with ionizing radiation, lithium chloride, and ethanol. Scientific report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1989-01-01

The pre-exposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride, and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired pre-exposures to lithium chloride blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiationmore » or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.« less

Roles of Octopamine and Dopamine Neurons for Mediating Appetitive and Aversive Signals in Pavlovian Conditioning in Crickets

PubMed Central

Mizunami, Makoto; Matsumoto, Yukihisa

2017-01-01

Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of “blocking” and “auto-blocking” phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals. PMID:29311961

Roles of Octopamine and Dopamine Neurons for Mediating Appetitive and Aversive Signals in Pavlovian Conditioning in Crickets.

PubMed

Mizunami, Makoto; Matsumoto, Yukihisa

2017-01-01

Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of "blocking" and "auto-blocking" phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals.

Stress enables reinforcement-elicited serotonergic consolidation of fear memory

PubMed Central

Baratta, Michael V.; Kodandaramaiah, Suhasa B.; Monahan, Patrick E.; Yao, Junmei; Weber, Michael D.; Lin, Pei-Ann; Gisabella, Barbara; Petrossian, Natalie; Amat, Jose; Kim, Kyungman; Yang, Aimei; Forest, Craig R.; Boyden, Edward S.; Goosens, Ki A.

2015-01-01

Background Prior exposure to stress is a risk factor for developing post-traumatic stress disorder (PTSD) in response to trauma, yet the mechanisms by which this occurs are unclear. Using a rodent model of stress-based susceptibility to PTSD, we investigated the role of serotonin in this phenomenon. Methods Adult mice were exposed to repeated immobilization stress or handling, and the role of serotonin in subsequent fear learning was assessed using pharmacological manipulation and western blot detection of serotonin receptors, measurements of serotonin, high-speed optogenetic silencing, and behavior. Results Both dorsal raphe serotonergic activity during aversive reinforcement and amygdala serotonin 2c receptor (5-HT2CR) activity during memory consolidation are necessary for stress enhancement of fear memory, but neither process affects fear memory in unstressed mice. Additionally, prior stress increases amygdala sensitivity to serotonin by promoting surface expression of 5-HT2CR without affecting tissue levels of serotonin in the amygdala. We also show that the serotonin that drives stress enhancement of associative cued fear memory can arise from paired or unpaired footshock, an effect not predicted by theoretical models of associative learning. Conclusion Stress bolsters the consequences of aversive reinforcement, not by simply enhancing the neurobiological signals used to encode fear in unstressed animals, but rather by engaging distinct mechanistic pathways. These results reveal that predictions from classical associative learning models do not always hold for stressed animals, and suggest that 5-HT2CR blockade may represent a promising therapeutic target for psychiatric disorders characterized by excessive fear responses such as that observed in PTSD. PMID:26248536

Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment

PubMed Central

Birmes, Philippe; Ferry, Barbara

2018-01-01

Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the “city-like” test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans. PMID:29352277

Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.

PubMed

Villain, Hélène; Benkahoul, Aïcha; Birmes, Philippe; Ferry, Barbara; Roullet, Pascal

2018-01-01

Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the "city-like" test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.

Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

PubMed

Goodfellow, Molly J; Lindquist, Derick H

2014-09-01

In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock. © 2014 Wiley Periodicals, Inc.

Cocaine Drives Aversive Conditioning via Delayed Activation of Dopamine-Responsive Habenular and Midbrain Pathways

PubMed Central

Good, Cameron H.; Rowley, Courtney S.; Xu, Sheng-ping; Wang, Huikun; Burnham, Nathan W.; Hoffman, Alexander F.; Lupica, Carl R.; Ikemoto, Satoshi

2013-01-01

Many strong rewards, including abused drugs, also produce aversive effects that are poorly understood. For example, cocaine can produce aversive conditioning after its rewarding effects have dissipated, consistent with opponent process theory, but the neural mechanisms involved are not well known. Using electrophysiological recordings in awake rats, we found that some neurons in the lateral habenula (LHb), where activation produces aversive conditioning, exhibited biphasic responses to single doses of intravenous cocaine, with an initial inhibition followed by delayed excitation paralleling cocaine's shift from rewarding to aversive. Recordings in LHb slice preparations revealed similar cocaine-induced biphasic responses and further demonstrated that biphasic responses were mimicked by dopamine, that the inhibitory phase depended on dopamine D2-like receptors, and that the delayed excitation persisted after drug washout for prolonged durations consistent with findings in vivo. c-Fos experiments further showed that cocaine-activated LHb neurons preferentially projected to and activated neurons in the rostromedial tegmental nucleus (RMTg), a recently identified target of LHb axons that is activated by negative motivational stimuli and inhibits dopamine neurons. Finally, pharmacological excitation of the RMTg produced conditioned place aversion, whereas cocaine-induced avoidance behaviors in a runway operant paradigm were abolished by lesions of LHb efferents, lesions of the RMTg, or by optogenetic inactivation of the RMTg selectively during the period when LHb neurons are activated by cocaine. Together, these results indicate that LHb/RMTg pathways contribute critically to cocaine-induced avoidance behaviors, while also participating in reciprocally inhibitory interactions with dopamine neurons. PMID:23616555

Lesions of the rat nucleus basalis magnocellularis disrupt appetitive-to-aversive transfer learning.

PubMed

Butt, A E; Schultz, J A; Arnold, L L; Garman, E E; George, C L; Garraghty, P E

2003-01-01

Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.

Animal models.

PubMed

Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Prefrontal/accumbal catecholamine system processes high motivational salience

PubMed Central

Puglisi-Allegra, Stefano; Ventura, Rossella

2012-01-01

Motivational salience regulates the strength of goal seeking, the amount of risk taken, and the energy invested from mild to extreme. Highly motivational experiences promote highly persistent memories. Although this phenomenon is adaptive in normal conditions, experiences with extremely high levels of motivational salience can promote development of memories that can be re-experienced intrusively for long time resulting in maladaptive outcomes. Neural mechanisms mediating motivational salience attribution are, therefore, very important for individual and species survival and for well-being. However, these neural mechanisms could be implicated in attribution of abnormal motivational salience to different stimuli leading to maladaptive compulsive seeking or avoidance. We have offered the first evidence that prefrontal cortical norepinephrine (NE) transmission is a necessary condition for motivational salience attribution to highly salient stimuli, through modulation of dopamine (DA) in the nucleus accumbens (NAc), a brain area involved in all motivated behaviors. Moreover, we have shown that prefrontal-accumbal catecholamine (CA) system determines approach or avoidance responses to both reward- and aversion-related stimuli only when the salience of the unconditioned stimulus (UCS) is high enough to induce sustained CA activation, thus affirming that this system processes motivational salience attribution selectively to highly salient events. PMID:22754514

Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

PubMed Central

Noble, Emily E.; Mavanji, Vijayakumar; Little, Morgan R.; Billington, Charles J.; Kotz, Catherine M.; Wang, ChuanFeng

2014-01-01

Background Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for seven weeks of exercise intervention. Results Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. PMID:24755094

Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.

PubMed

Noble, Emily E; Mavanji, Vijayakumar; Little, Morgan R; Billington, Charles J; Kotz, Catherine M; Wang, ChuanFeng

2014-10-01

Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7 weeks of exercise intervention. Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. Published by Elsevier Inc.

Role of the Bed Nucleus of the Stria Terminalis in Aversive Learning and Memory

ERIC Educational Resources Information Center

Goode, Travis D.; Maren, Stephen

2017-01-01

Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and for coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, and freezing behavior). The bed nucleus of the stria terminalis (BNST) is a critical interface between the "affective…

RSK2 Signaling in Brain Habenula Contributes to Place Aversion Learning

ERIC Educational Resources Information Center

Darcq, Emmanuel; Koebel, Pascale; Del Boca, Carolina; Pannetier, Solange; Kirstetter, Anne-Sophie; Garnier, Jean-Marie; Hanauer, Andre; Befort, Katia; Kieffer, Brigitte L.

2011-01-01

RSK2 is a Ser/Thr kinase acting in the Ras/MAPK pathway. "Rsk2" gene deficiency leads to the Coffin-Lowry Syndrome, notably characterized by cognitive deficits. We found that "mrsk2" knockout mice are unable to associate an aversive stimulus with context in a lithium-induced conditioned place aversion task requiring both high-order cognition and…

Dine or dash? Turbulence inhibits blue crab navigation in attractive-aversive odor plumes by altering signal structure encoded by the olfactory pathway.

PubMed

Weissburg, Marc; Atkins, Lorin; Berkenkamp, Kimberly; Mankin, Danielle

2012-12-01

Blue crabs can distinguish and navigate to attractive (food) odors even when aversive odors (injured crab metabolites) are released nearby. Blue crabs in these conditions detect the aversive odor and avoid it, but find the attractive source with nearly the same success rate as when the attractive source is presented alone. Spatially and temporally distinct odor filaments appear to signal to foragers that the two odor sources are not co-located, and hence navigating to the attractive odor entails an acceptable risk of predation. However, environmentally produced turbulence suppresses tracking by homogenizing the two odors; blue crabs fail to track to the attractive source when the aversive source is present, even though turbulence does not substantially inhibit tracking to the attractive source alone. Removal of sensory input from aesthetascs on the antennules, but not chemosensors on the legs, rescues navigation to attractive-aversive dual plumes in turbulent conditions. These results suggest that mixing in the natural environment may amplify the effects of predators by suppressing tracking to food odors when aversive cues are present, and that the olfactory pathway mediates the response.

Extended lowered body temperature increases the effective CS-US interval in conditioned taste aversion for adult rats.

PubMed

Hinderliter, Charles F; Goodhart, Mark; Anderson, Matthew J; Misanin, James R

2002-06-01

Assuming body temperature correlates with metabolic activities, rate of body temperature recovery was manipulated to assess effects on long-trace conditioning in a conditioned taste-aversion paradigm. Following 10 min. access to a .1% saccharin solution and then 10 min. immersion in 0-0.5 degrees C water, two groups of 16 Wistar-derived, 81-113 day-old, male albino rats received either saline or lithium chloride injections 3 hr. later. These two groups were subdivided on basis of warming rate during the 3-hr. interval. Half of the rats recovered at room temperature (20 degrees to 21 degrees C), and half recovered in an incubator maintained at 30 degrees C. Maintaining a lowered body temperature between the conditioned stimulus and unconditioned stimulus allowed an association to be made at 3 hr., an interval that normally does not support conditioning. In contrast, lowering body temperature and then inducing a fast warming rate did not produce evidence of an aversion. It is suggested that maintaining a low body temperature over the interval between the presentation of the conditioned stimulus and unconditioned stimulus slows a metabolic clock that extends the measured interval at which associations can be made using conditioned taste-aversion procedures.

The Influence of Prior Handling on the Effective CS-US Interval in Long-Trace Taste-Aversion Conditioning in Rats

ERIC Educational Resources Information Center

Hinderliter, Charles F.; Andrews, Amy; Misanin, James R.

2012-01-01

In conditioned taste aversion (CTA), a taste, the conditioned stimulus (CS), is paired with an illness-inducing stimulus, the unconditioned stimulus (US), to produce CS-US associations at very long (hours) intervals, a result that appears to violate the law of contiguity. The specific length of the maximum effective trace interval that has been…

AAB and ABA Renewal as a Function of the Number of Extinction Trials in Conditioned Taste Aversion

ERIC Educational Resources Information Center

Rosas, Juan M.; Garcia-Gutierrez, Ana; Callejas-Aguilera, Jose E.

2007-01-01

Three experiments explored renewal in conditioned taste aversion after different amounts of extinction. In Experiment 1, three groups of rats received a single conditioning trial where a saccharin solution was paired with LiCl, followed by 3 extinction trials, and a two-trial test. Groups differed in the context where they received each of the…

Neural Correlates of Appetitive-Aversive Interactions in Pavlovian Fear Conditioning

ERIC Educational Resources Information Center

Nasser, Helen M.; McNally, Gavan P.

2013-01-01

We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive-aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS)-food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of…

Conditioned food aversion to control poisoning by Ipomoea carnea subsp. fistulosa in goats

USDA-ARS?s Scientific Manuscript database

Ipomoea carnea is a toxic plant often ingested by livestock in Brazil. Three experiments were conducted to determine if conditioned food aversion was effective in reducing goats’ consumption of I. carnea. In the fi rst experiment, 10 mildly intoxicated goats that had been eating I. carnea were avert...

Temporary Basolateral Amygdala Lesions Disrupt Acquisition of Socially Transmitted Food Preferences in Rats

ERIC Educational Resources Information Center

Fontanini, Alfredo; Katz, Donald B.; Wang, Yunyan

2006-01-01

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in…

Conditioned suppression, punishment, and aversion

NASA Technical Reports Server (NTRS)

Orme-Johnson, D. W.; Yarczower, M.

1974-01-01

The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model.

PubMed

Pautassi, Ricardo M; Nizhnikov, Michael E; Spear, Norman E

2009-06-01

The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects.

Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model

PubMed Central

Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.

2009-01-01

The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects. PMID:19428502

Investigating the Predictive Value of Functional MRI to Appetitive and Aversive Stimuli: A Pattern Classification Approach.

PubMed

McCabe, Ciara; Rocha-Rego, Vanessa

2016-01-01

Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder.

Learning shapes the aversion and reward responses of lateral habenula neurons

PubMed Central

Wang, Daqing; Li, Yi; Feng, Qiru; Guo, Qingchun; Zhou, Jingfeng; Luo, Minmin

2017-01-01

The lateral habenula (LHb) is believed to encode negative motivational values. It remains unknown how LHb neurons respond to various stressors and how learning shapes their responses. Here, we used fiber-photometry and electrophysiology to track LHb neuronal activity in freely-behaving mice. Bitterness, pain, and social attack by aggressors intensively excite LHb neurons. Aversive Pavlovian conditioning induced activation by the aversion-predicting cue in a few trials. The experience of social defeat also conditioned excitatory responses to previously neutral social stimuli. In contrast, fiber photometry and single-unit recordings revealed that sucrose reward inhibited LHb neurons and often produced excitatory rebound. It required prolonged conditioning and high reward probability to induce inhibition by reward-predicting cues. Therefore, LHb neurons can bidirectionally process a diverse array of aversive and reward signals. Importantly, their responses are dynamically shaped by learning, suggesting that the LHb participates in experience-dependent selection of behavioral responses to stressors and rewards. DOI: http://dx.doi.org/10.7554/eLife.23045.001 PMID:28561735

Genotype Modulates Age-Related Alterations in Sensitivity to the Aversive Effects of Ethanol: An 8 Inbred Strain Analysis of Conditioned Taste Aversion

PubMed Central

Moore, Eileen M.; Forrest, Robert D.; Boehm, Stephen L.

2012-01-01

Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Thus far there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in 8 inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1h. Immediately following access mice were administered ethanol (0, 1.5, 2.25, 3g/kg, ip). This procedure was repeated in 72h intervals for a total of 5 CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. PMID:23171343

Reconciling the role of serotonin in behavioral inhibition and aversion: acute tryptophan depletion abolishes punishment-induced inhibition in humans

PubMed Central

Crockett, Molly J.; Clark, Luke; Robbins, Trevor W.

2009-01-01

The neuromodulator serotonin has been implicated in a large number of affective and executive functions, but its precise contribution to motivation remains unclear. One influential hypothesis has implicated serotonin in aversive processing; another has proposed a more general role for serotonin in behavioral inhibition. Since behavioral inhibition is a pre-potent reaction to aversive outcomes, it has been a challenge to reconcile these two accounts. Here, we show that serotonin is critical for punishment-induced inhibition, but not overall motor response inhibition or reporting aversive outcomes. We used acute tryptophan depletion to temporarily lower brain serotonin in healthy human volunteers as they completed a novel task designed to obtain separate measures of motor response inhibition, punishment-induced inhibition, and sensitivity to aversive outcomes. Following a placebo treatment, participants were slower to respond under punishment conditions, compared to reward conditions. Tryptophan depletion abolished this punishment-induced inhibition, without affecting overall motor response inhibition or the ability to adjust response bias in line with punishment contingencies. The magnitude of reduction in punishment-induced inhibition depended on the degree to which tryptophan depletion reduced plasma tryptophan levels. These findings extend and clarify previous research on the role of serotonin in aversive processing and behavioral inhibition, and fit with current theorizing on serotonin's involvement in predicting aversive outcomes. PMID:19776285

The "memory kinases": roles of PKC isoforms in signal processing and memory formation.

PubMed

Sun, Miao-Kun; Alkon, Daniel L

2014-01-01

The protein kinase C (PKC) isoforms, which play an essential role in transmembrane signal conduction, can be viewed as a family of "memory kinases." Evidence is emerging that they are critically involved in memory acquisition and maintenance, in addition to their involvement in other functions of cells. Deficits in PKC signal cascades in neurons are one of the earliest abnormalities in the brains of patients suffering from Alzheimer's disease. Their dysfunction is also involved in several other types of memory impairments, including those related to emotion, mental retardation, brain injury, and vascular dementia/ischemic stroke. Inhibition of PKC activity leads to a reduced capacity of many types of learning and memory, but may have therapeutic values in treating substance abuse or aversive memories. PKC activators, on the other hand, have been shown to possess memory-enhancing and antidementia actions. PKC pharmacology may, therefore, represent an attractive area for developing effective cognitive drugs for the treatment of many types of memory disorders and dementias. © 2014 Elsevier Inc. All rights reserved.

Examining Object Location and Object Recognition Memory in Mice

PubMed Central

Vogel-Ciernia, Annie; Wood, Marcelo A.

2014-01-01

Unit Introduction The ability to store and recall our life experiences defines a person's identity. Consequently, the loss of long-term memory is a particularly devastating part of a variety of cognitive disorders, diseases and injuries. There is a great need to develop therapeutics to treat memory disorders, and thus a variety of animal models and memory paradigms have been developed. Mouse models have been widely used both to study basic disease mechanisms and to evaluate potential drug targets for therapeutic development. The relative ease of genetic manipulation of Mus musculus has led to a wide variety of genetically altered mice that model cognitive disorders ranging from Alzheimer's disease to autism. Rodents, including mice, are particularly adept at encoding and remembering spatial relationships, and these long-term spatial memories are dependent on the medial temporal lobe of the brain. These brain regions are also some of the first and most heavily impacted in disorders of human memory including Alzheimer's disease. Consequently, some of the simplest and most commonly used tests of long-term memory in mice are those that examine memory for objects and spatial relationships. However, many of these tasks, such as Morris water maze and contextual fear conditioning, are dependent upon the encoding and retrieval of emotionally aversive and inherently stressful training events. While these types of memories are important, they do not reflect the typical day-to-day experiences or memories most commonly affected in human disease. In addition, stress hormone release alone can modulate memory and thus obscure or artificially enhance these types of tasks. To avoid these sorts of confounds, we and many others have utilized tasks testing animals’ memory for object location and novel object recognition. These tasks involve exploiting rodents’ innate preference for novelty, and are inherently not stressful. In this protocol we detail how memory for object location and object identity can be used to evaluate a wide variety of mouse models and treatments. PMID:25297693

An overview of translationally informed treatments for PTSD: animal models of Pavlovian fear conditioning to human clinical trials

PubMed Central

Bowers, Mallory E.; Ressler, Kerry J.

2015-01-01

Posttraumatic stress disorder (PTSD) manifests after exposure to a traumatic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect dysregulation of the fear system likely caused by poor fear inhibition/extinction, increased generalization, and/or enhanced consolidation or acquisition of fear. These phenotypes can be modeled in animal subjects using Pavlovian fear conditioning, allowing investigation of the underlying neurobiology of normative and pathological fear. Pre-clinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory, which have informed the development of therapies used in human clinical trials. In this review, we discuss the evidence for a number of established and emerging pharmacotherapies and device-based treatments for PTSD that have been developed via a bench to bedside translational model. PMID:26238379

Juvenile stress potentiates aversive 22-kHz ultrasonic vocalizations and freezing during auditory fear conditioning in adult male rats.

PubMed

Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Wöhr, Markus

2012-09-01

Traumatic experiences that occur during adolescence can render individuals vulnerable to mood and anxiety disorders. A model in juvenile rats (age: 27-29 days) was developed previously to study the long-term effects of adolescent stress exposure on behaviour and physiology. This paradigm, termed juvenile stress, involves subjecting juvenile rats to different stressors on consecutive days over a 3-day period. Here, we investigated the effects of the juvenile stress paradigm on freezing behaviour and aversive 22-kHz ultrasonic vocalizations (USVs) during auditory fear conditioning in adult male rats (age: 68-90 days). We found that rats previously subjected to juvenile stress increased aversive 22-kHz USVs (total calls and time spent calling) compared with controls during fear-conditioning training. The acoustic USV parameters between control and juvenile stress rats were largely equivalent, including duration, peak frequency and amplitude. While rats did not differ in freezing behaviour during fear conditioning, juvenile stress rats exhibited greater cue-conditioned freezing upon testing 24 h later. Our results show that juvenile stress elicited different long-term changes in freezing and aversive USVs during fear conditioning. Furthermore, they highlight the importance of assessing USVs to detect experience-dependent differences between control and stress-exposed animals which are not detectable by measuring visible behaviour.

Ventral Pallidum Encodes Contextual Information and Controls Aversive Behaviors.

PubMed

Saga, Yosuke; Richard, Augustin; Sgambato-Faure, Véronique; Hoshi, Eiji; Tobler, Philippe N; Tremblay, Léon

2017-04-01

Successful avoidance of aversive outcomes is crucial for the survival of animals. Although accumulating evidence indicates that an indirect pathway in the basal ganglia is involved in aversive behavior, the ventral pallidum (VP), which is an important component of this pathway, has so far been implicated primarily in appetitive behavior. In this study, we used single-cell recordings and bicuculline (GABAA antagonist) injections to elucidate the role of VP both in the encoding of aversive context and in active avoidance. We found 2 populations of neurons that were preferentially activated by appetitive and aversive conditioned stimuli (CSs). In addition, VP showed appetitive and aversive outcome anticipatory activities. These activity patterns indicate that VP is involved in encoding and maintaining CS-induced aversive contextual information. Furthermore, the disturbance of VP activity by bicuculline injection increased the number of error trials in aversive trials. In particular, the subjects released the response bar prematurely, showed no response at all, or failed to avoid the aversive outcome. Overall, these results suggest that VP plays a central role in controlling CS-induced negative motivation to produce avoidance behavior. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Attenuation and cross-attenuation in taste aversion learning in the rat: Studies with ionizing radiation, lithium chloride and ethanol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1988-12-01

The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO)more » disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.« less

Attenuation and cross-attenuation in taste aversion learning in the rat: studies with ionizing radiation, lithium chloride and ethanol.

PubMed

Rabin, B M; Hunt, W A; Lee, J

1988-12-01

The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO) disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.

The differential role of cortical protein synthesis in taste memory formation and persistence

NASA Astrophysics Data System (ADS)

Levitan, David; Gal-Ben-Ari, Shunit; Heise, Christopher; Rosenberg, Tali; Elkobi, Alina; Inberg, Sharon; Sala, Carlo; Rosenblum, Kobi

2016-05-01

The current dogma suggests that the formation of long-term memory (LTM) is dependent on protein synthesis but persistence of the memory trace is not. However, many of the studies examining the effect of protein synthesis inhibitors (PSIs) on LTM persistence were performed in the hippocampus, which is known to have a time-dependent role in memory storage, rather than the cortex, which is considered to be the main structure to store long-term memories. Here we studied the effect of PSIs on LTM formation and persistence in male Wistar Hola (n⩾5) rats by infusing the protein synthesis inhibitor, anisomycin (100 μg, 1 μl), into the gustatory cortex (GC) during LTM formation and persistence in conditioned taste aversion (CTA). We found that local anisomycin infusion to the GC before memory acquisition impaired LTM formation (P=8.9E-5), but had no effect on LTM persistence when infused 3 days post acquisition (P=0.94). However, when we extended the time interval between treatment with anisomycin and testing from 3 days to 14 days, LTM persistence was enhanced (P=0.01). The enhancement was on the background of stable and non-declining memory, and was not recapitulated by another amnesic agent, APV (10 μg, 1 μl), an N-methyl-D-aspartate receptor antagonist (P=0.54). In conclusion, CTA LTM remains sensitive to the action of PSIs in the GC even 3 days following memory acquisition. This sensitivity is differentially expressed between the formation and persistence of LTM, suggesting that increased cortical protein synthesis promotes LTM formation, whereas decreased protein synthesis promotes LTM persistence.

Disentangling the Effects of Context Change and Context Familiarity on Latent Inhibition with a Conditioned Taste Aversion Procedure

ERIC Educational Resources Information Center

De la Casa, L. G.; Mena, A.; Orgaz, A.; Fernandez, A.

2013-01-01

Contextual specificity of Latent Inhibition (LI) has been demonstrated using an ample range of experimental procedures. Context dependence has not been consistently obtained, however, when LI has been induced using a Conditioned Taste Aversion (CTA) procedure. This paper presents two experiments designed to analyze whether the context plays the…

Conditioned food aversion to control outbreaks of intoxication by Ipomoea carnea and Turbina cordata in goats

USDA-ARS?s Scientific Manuscript database

Conditioned food aversion is used to train livestock to avoid the ingestion of toxic plants. This technique was used to control Turbina cordata poisoning in goats in one farm, and to control Ipomoea carnea subsp. istulosa poisoning in another farm. The goats were penned at night and the next mornin...

Infantile Amnesia: A Critical Period of Learning to Learn and Remember

PubMed Central

Travaglia, Alessio

2017-01-01

Infantile amnesia, the inability of adults to recollect early episodic memories, is associated with the rapid forgetting that occurs in childhood. It has been suggested that infantile amnesia is due to the underdevelopment of the infant brain, which would preclude memory consolidation, or to deficits in memory retrieval. Although early memories are inaccessible to adults, early-life events, such as neglect or aversive experiences, can greatly impact adult behavior and may predispose individuals to various psychopathologies. It remains unclear how a brain that rapidly forgets, or is not yet able to form long-term memories, can exert such a long-lasting and important influence. Here, with a particular focus on the hippocampal memory system, we review the literature and discuss new evidence obtained in rats that illuminates the paradox of infantile amnesia. We propose that infantile amnesia reflects a developmental critical period during which the learning system is learning how to learn and remember. PMID:28615475

The effects of continuous and intermittent ethanol exposure in adolesence on the aversive properties of ethanol during adulthood.

PubMed

Diaz-Granados, Jaime L; Graham, Danielle L

2007-12-01

Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol. The present study was designed to examine whether ethanol exposure, continuous versus intermittent, during the adolescent developmental period would alter the aversive properties of ethanol in adult C3H mice. Periadolescent (PD28) male C3H mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion conditioning was carried out on both ethanol pre-exposed and ethanol-naive animals using a 1-trial, 1-flavor taste-conditioning procedure. Ethanol exposure during the periadolescent period significantly attenuated a subsequent ethanol-induced conditioned taste aversion, as compared with control animals. Adult animals exposed to chronic ethanol vapor during adolescence showed less of an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent exposure to ethanol vapor during periadolescence produced a greater attenuation. It is suggested that ethanol exposure during the periadolescent period results in long-term neurobehavioral changes, which lessen a conditioned aversion to ethanol in adulthood. It is suggested that this age-related effect may underlie the increased susceptibility to alcohol-related problems which is negatively correlated with the age of onset for alcohol abuse.

Chronic pain induces generalized enhancement of aversion

PubMed Central

Zhang, Qiaosheng; Manders, Toby; Tong, Ai Phuong; Yang, Runtao; Garg, Arpan; Martinez, Erik; Zhou, Haocheng; Dale, Jahrane; Goyal, Abhinav; Urien, Louise; Yang, Guang; Chen, Zhe; Wang, Jing

2017-01-01

A hallmark feature of chronic pain is its ability to impact other sensory and affective experiences. It is notably associated with hypersensitivity at the site of tissue injury. It is less clear, however, if chronic pain can also induce a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs. Here, we showed that chronic pain in one limb in rats increased the aversive response to acute pain stimuli in the opposite limb, as assessed by conditioned place aversion. Interestingly, neural activities in the anterior cingulate cortex (ACC) correlated with noxious intensities, and optogenetic modulation of ACC neurons showed bidirectional control of the aversive response to acute pain. Chronic pain, however, altered acute pain intensity representation in the ACC to increase the aversive response to noxious stimuli at anatomically unrelated sites. Thus, chronic pain can disrupt cortical circuitry to enhance the aversive experience in a generalized anatomically nonspecific manner. DOI: http://dx.doi.org/10.7554/eLife.25302.001 PMID:28524819

Five-year-olds do not show ambiguity aversion in a risk and ambiguity task with physical objects.

PubMed

Li, Rosa; Roberts, Rachel C; Huettel, Scott A; Brannon, Elizabeth M

2017-07-01

Ambiguity aversion arises when a decision maker prefers risky gambles with known probabilities over equivalent ambiguous gambles with unknown probabilities. This phenomenon has been consistently observed in adults across a large body of empirical work. Evaluating ambiguity aversion in young children, however, has posed methodological challenges because probabilistic representations appropriate for adults might not be understood by young children. Here, we established a novel method for representing risk and ambiguity with physical objects that overcomes previous methodological limitations and allows us to measure ambiguity aversion in young children. We found that individual 5-year-olds exhibited consistent choice preferences and, as a group, exhibited no ambiguity aversion in a task that evokes ambiguity aversion in adults. Across individuals, 5-year-olds exhibited greater variance in ambiguity preferences compared with adults tested under similar conditions. This suggests that ambiguity aversion is absent during early childhood and emerges over the course of development. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat.

PubMed

Di Scala, G; Mana, M J; Jacobs, W J; Phillips, A G

1987-01-01

Stimulation of the periaqueductal grey (PAG) has been used to support aversive conditioning in a variety of species with several experimental paradigms. However, it has not been clearly demonstrated whether the behavioral changes produced by PAG stimulation in these paradigms are mediated by associative or nonassociative mechanisms. The present studies demonstrate that electrical stimulation of the PAG in the rat may be used to support associative learning in a Pavlovian paradigm. In each experiment, a fully controlled conditional emotional response (CER) procedure was used to examine the unconditional aversive properties of PAG stimulation. In Experiment 1a, weak associative conditioning was observed when a light CS was paired with PAG stimulation over 6 conditioning trials. In Experiment 1b, robust associative conditioning was obtained with a light CS when 18 conditioning trials were used. In Experiment 2, robust associative conditioning was demonstrated with a tone CS when 6 conditioning trials were used. The results parallel those found when other aversive stimuli are used as a UCS (e.g., footshock or intraorbital air puff), and because the present experiments included the proper control procedures the results clearly indicate that the behavioral changes produced by PAG stimulation are mediated by associative Pavlovian learning mechanisms rather than nonassociative mechanisms such as sensitization or pseudoconditioning. The present technique may be useful for assessing the neuroanatomical and neurochemical substrates underlying the aversive effects of brain-stimulation, and for screening the effects of drugs on the conditional and unconditional responses produced by such stimulation.

Lesions of the Lateral Habenula Increase Voluntary Ethanol Consumption and Operant Self-Administration, Block Yohimbine-Induced Reinstatement of Ethanol Seeking, and Attenuate Ethanol-Induced Conditioned Taste Aversion

PubMed Central

Schwager, Andrea L.; Sinclair, Michael S.; Tandon, Shashank; Taha, Sharif A.

2014-01-01

The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug. PMID:24695107

Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.

PubMed

Haack, Andrew K; Sheth, Chandni; Schwager, Andrea L; Sinclair, Michael S; Tandon, Shashank; Taha, Sharif A

2014-01-01

The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

Clozapine and Olanzapine Exhibit an Intrinsic Anxiolytic Property in Two Conditioned Fear Paradigms: Contrast with Haloperidol and Chlordiazepoxide

PubMed Central

Mead, Alexa; Li, Ming; Kapur, Shitij

2008-01-01

Psychotic fear and anxiety disturbances are seen at a relatively high frequency in patients with schizophrenia. Atypical antipsychotics are believed to show superior efficacy in reducing these symptoms. However, clinical and preclinical evidence regarding their anxiolytic efficacy has been mixed. In this study, we evaluated the possible anxiolytic property of two atypicals clozapine and olanzapine and compared them with typical haloperidol and chlordiazepoxide (a prototype of sedative-anxiolytic drug) in two preclinical models of fear. In Experiment 1, we used a fear-induced passive avoidance and conditioned place aversion paradigm and examined the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc) and chlordiazepoxide (10 mg/kg, ip). In Experiments 2 and 3, we used a two-way active avoidance conditioning paradigm and further compared the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc), chlordiazepoxide (10 mg/kg, ip) and three doses of olanzapine (0.5, 1.0, and 2.0 mg/kg, sc). Results show that clozapine and chlordiazepoxide, but not haloperidol, significantly attenuated the shock conditioning-induced place aversion, decreased the amount of defecations and the number of the 22 kHz vocalizations. Clozapine also reduced the shock conditioning-induced hyperthermia. Similar to clozapine, olanzapine also significantly decreased the amount of defecations and reduced the shock conditioning-induced hyperthermia, but it did not inhibit the 22 kHz vocalizations. This study demonstrates that clozapine and olanzapine possess an intrinsic anxiolytic property, which is not attributable to its superior anti-“psychotic” effect or its favorable effects on motor functions or learning and memory processes. These findings also suggest that the combined use of passive avoidance and active avoidance conditioning models can be useful in better differentiating typical and atypical antipsychotics as well as anxiolytics. PMID:18547622

Dopaminergic neurons write and update memories with cell-type-specific rules

PubMed Central

Aso, Yoshinori; Rubin, Gerald M

2016-01-01

Associative learning is thought to involve parallel and distributed mechanisms of memory formation and storage. In Drosophila, the mushroom body (MB) is the major site of associative odor memory formation. Previously we described the anatomy of the adult MB and defined 20 types of dopaminergic neurons (DANs) that each innervate distinct MB compartments (Aso et al., 2014a, 2014b). Here we compare the properties of memories formed by optogenetic activation of individual DAN cell types. We found extensive differences in training requirements for memory formation, decay dynamics, storage capacity and flexibility to learn new associations. Even a single DAN cell type can either write or reduce an aversive memory, or write an appetitive memory, depending on when it is activated relative to odor delivery. Our results show that different learning rules are executed in seemingly parallel memory systems, providing multiple distinct circuit-based strategies to predict future events from past experiences. DOI: http://dx.doi.org/10.7554/eLife.16135.001 PMID:27441388

Processing speed and memory mediate age-related differences in decision making.

PubMed

Henninger, Debra E; Madden, David J; Huettel, Scott A

2010-06-01

Decision making under risk changes with age. Increases in risk aversion with age have been most commonly characterized, although older adults may be risk seeking in some decision contexts. An important, and unanswered, question is whether these changes in decision making reflect a direct effect of aging or, alternatively, an indirect effect caused by age-related changes in specific cognitive processes. In the current study, older adults (M = 71 years) and younger adults (M = 24 years) completed a battery of tests of cognitive capacities and decision-making preferences. The results indicated systematic effects of age upon decision quality-with both increased risk seeking and increased risk aversion observed in different tasks-consistent with prior studies. Path analyses, however, revealed that age-related effects were mediated by individual differences in processing speed and memory. When those variables were included in the model, age was no longer a significant predictor of decision quality. The authors conclude that the reduction in decision quality and associated changes in risk preferences commonly ascribed to aging are instead mediated by age-related changes in underlying cognitive capacities. (c) 2010 APA, all rights reserved

Peer effects in risk aversion.

PubMed

Balsa, Ana I; Gandelman, Néstor; González, Nicolás

2015-01-01

We estimate peer effects in risk attitudes in a sample of high school students. Relative risk aversion is elicited from surveys administered at school. Identification of peer effects is based on parents not being able to choose the class within the school of their choice, and on the use of instrumental variables conditional on school-grade fixed effects. We find a significant and quantitatively large impact of peers' risk attitudes on a male individual's coefficient of risk aversion. Specifically, a one standard deviation increase in the group's coefficient of risk aversion increases an individual's risk aversion by 43%. Our findings shed light on the origin and stability of risk attitudes and, more generally, on the determinants of economic preferences. © 2014 Society for Risk Analysis.

Worry-inducing stimuli in an aversive Go/NoGo task enhance reactive control in individuals with lower trait-anxiety.

PubMed

Leue, Anja; Rodilla, Carmen Cano; Beauducel, André

2017-04-01

This study relates predictions on reactive and proactive cognitive control to findings on anxious apprehension/worry and ERN/Ne. We investigated whether worry-inducing stimuli in an aversive performance setting lead to a more pronounced increase of the ERN/Ne in individuals with lower anxious apprehension/worry. We also explored the N2 amplitude in the context of worry-inducing stimuli. Fifty-eight participants performed an extended Go/NoGo task. A neutral or fearful face was presented at the beginning of each trial, with the fearful face as a worry-inducing, distracting stimulus. In an aversive feedback condition, aversive feedback was provided for false or too slow responses. We found a more pronounced decrease of the ERN/Ne after worry-inducing stimuli compared to neutral stimuli in participants with lower anxious apprehension/worry. Moreover, less pronounced N2 amplitudes were associated with shorter reaction times in the aversive feedback condition. Implications for future research on error monitoring and trait-anxiety are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving Dental Experiences by Using Virtual Reality Distraction: A Simulation Study

PubMed Central

Tanja-Dijkstra, Karin; Pahl, Sabine; P. White, Mathew; Andrade, Jackie; Qian, Cheng; Bruce, Malcolm; May, Jon; Moles, David R.

2014-01-01

Dental anxiety creates significant problems for both patients and the dental profession. Some distraction interventions are already used by healthcare professionals to help patients cope with unpleasant procedures. The present study is novel because it a) builds on evidence that natural scenery is beneficial for patients, and b) uses a Virtual Reality (VR) representation of nature to distract participants. Extending previous work that has investigated pain and anxiety during treatment, c) we also consider the longer term effects in terms of more positive memories of the treatment, building on a cognitive theory of memory (Elaborated Intrusions). Participants (n = 69) took part in a simulated dental experience and were randomly assigned to one of three VR conditions (active vs. passive vs. control). In addition, participants were distinguished into high and low dentally anxious according to a median split resulting in a 3×2 between-subjects design. VR distraction in a simulated dental context affected memories a week later. The VR distraction had effects not only on concurrent experiences, such as perceived control, but longitudinally upon the vividness of memories after the dental experience had ended. Participants with higher dental anxiety (for whom the dental procedures were presumably more aversive) showed a greater reduction in memory vividness than lower dental-anxiety participants. This study thus suggests that VR distractions can be considered as a relevant intervention for cycles of care in which people’s previous experiences affect their behaviour for future events. PMID:24621518

Enhanced startle responsivity 24 hours after acute stress exposure.

PubMed

Herten, Nadja; Otto, Tobias; Adolph, Dirk; Pause, Bettina M; Kumsta, Robert; Wolf, Oliver T

2016-10-01

Cortisol release in a stressful situation can be beneficial for memory encoding and memory consolidation. Stimuli, such as odors, related to the stressful episode may successfully cue memory contents of the stress experience. The current investigation aimed at testing the potency of stress to influence startle responsivity 24 hr later and to implicitly reactivate emotional memory traces triggered by an odor involved. Participants were assigned to either a stress (Trier Social Stress Test [TSST]) or control (friendly TSST [f-TSST]) condition featuring an ambient odor. On the next day, participants underwent an auditory startle paradigm while their eyeblink reflex was recorded by an electrooculogram. Three different olfactory stimuli were delivered, one being the target odor presented the day before. Additionally, negative, positive, and pictures of the committee members were included for comparing general startle responsivity and fear-potentiated startle. Participants of the stress group demonstrated an enhanced startle response across all stimuli compared to participants of the control group. There were no specific effects with regard to the target odor. The typical fear-potentiated startle response occurred. Stressed participants tended to rate the target odor more aversive than control participants. Odor recognition memory did not differ between the groups, suggesting an implicit effect on odor valence. Our results show that acute stress exposure enhances startle responsivity 24 hr later. This effect might be caused by a shift of amygdala function causing heightened sensitivity, but lower levels of specificity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Improving dental experiences by using virtual reality distraction: a simulation study.

PubMed

Tanja-Dijkstra, Karin; Pahl, Sabine; White, Mathew P; Andrade, Jackie; Qian, Cheng; Bruce, Malcolm; May, Jon; Moles, David R

2014-01-01

Dental anxiety creates significant problems for both patients and the dental profession. Some distraction interventions are already used by healthcare professionals to help patients cope with unpleasant procedures. The present study is novel because it a) builds on evidence that natural scenery is beneficial for patients, and b) uses a Virtual Reality (VR) representation of nature to distract participants. Extending previous work that has investigated pain and anxiety during treatment, c) we also consider the longer term effects in terms of more positive memories of the treatment, building on a cognitive theory of memory (Elaborated Intrusions). Participants (n = 69) took part in a simulated dental experience and were randomly assigned to one of three VR conditions (active vs. passive vs. control). In addition, participants were distinguished into high and low dentally anxious according to a median split resulting in a 3×2 between-subjects design. VR distraction in a simulated dental context affected memories a week later. The VR distraction had effects not only on concurrent experiences, such as perceived control, but longitudinally upon the vividness of memories after the dental experience had ended. Participants with higher dental anxiety (for whom the dental procedures were presumably more aversive) showed a greater reduction in memory vividness than lower dental-anxiety participants. This study thus suggests that VR distractions can be considered as a relevant intervention for cycles of care in which people's previous experiences affect their behaviour for future events.

Preexposure to salty and sour taste enhances conditioned taste aversion to novel sucrose

PubMed Central

Flores, Veronica L.; Moran, Anan; Bernstein, Max

2016-01-01

Conditioned taste aversion (CTA) is an intensively studied single-trial learning paradigm whereby animals are trained to avoid a taste that has been paired with malaise. Many factors influence the strength of aversion learning; prominently studied among these is taste novelty—the fact that preexposure to the taste conditioned stimulus (CS) reduces its associability. The effect of exposure to tastes other than the CS has, in contrast, received little investigation. Here, we exposed rats to sodium chloride (N) and citric acid (C), either before or within a conditioning session involving novel sucrose (S). Presentation of this taste array within the conditioning session weakened the resultant S aversion, as expected. The opposite effect, however, was observed when exposure to the taste array was provided in sessions that preceded conditioning: such experience enhanced the eventual S aversion—a result that was robust to differences in CS delivery method and number of tastes presented in conditioning sessions. This “non-CS preexposure effect” scaled with the number of tastes in the exposure array (experience with more stimuli was more effective than experience with fewer) and with the amount of exposure sessions (three preexposure sessions were more effective than two). Together, our results provide evidence that exposure and experience with the realm of tastes changes an animal's future handling of even novel tastes. PMID:27084929

Effects of voluntary and treadmill exercise on spontaneous withdrawal signs, cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats.

PubMed

Mokhtari-Zaer, Amin; Ghodrati-Jaldbakhan, Shahrbanoo; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Akhavan, Maziar M; Bandegi, Ahmad Reza; Rashidy-Pour, Ali

2014-09-01

Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Prepared stimuli enhance aversive learning without weakening the impact of verbal instructions

PubMed Central

2018-01-01

Fear-relevant stimuli such as snakes and spiders are thought to capture attention due to evolutionary significance. Classical conditioning experiments indicate that these stimuli accelerate learning, while instructed extinction experiments suggest they may be less responsive to instructions. We manipulated stimulus type during instructed aversive reversal learning and used quantitative modeling to simultaneously test both hypotheses. Skin conductance reversed immediately upon instruction in both groups. However, fear-relevant stimuli enhanced dynamic learning, as measured by higher learning rates in participants conditioned with images of snakes and spiders. Results are consistent with findings that dissociable neural pathways underlie feedback-driven and instructed aversive learning. PMID:29339561

Cognitive Decline Is Associated with Risk Aversion and Temporal Discounting in Older Adults without Dementia

PubMed Central

James, Bryan D.; Boyle, Patricia A.; Yu, Lei; Han, S. Duke; Bennett, David A.

2015-01-01

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that subtle age-related changes in cognition can detrimentally affect individual preferences that are critical for maintaining health and well being. PMID:25838074

Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

PubMed

James, Bryan D; Boyle, Patricia A; Yu, Lei; Han, S Duke; Bennett, David A

2015-01-01

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that subtle age-related changes in cognition can detrimentally affect individual preferences that are critical for maintaining health and well being.

Further evidence for conditioned taste aversion induced by forced swimming.

PubMed

Masaki, Takahisa; Nakajima, Sadahiko

2005-01-31

A series of experiments with rats reported that aversion to a taste solution can be established by forced swimming in a water pool. Experiment 1 demonstrated that correlation of taste and swimming is a critical factor for this phenomenon, indicating associative (i.e., Pavlovian) nature of this learning. Experiment 2 showed that this learning obeys the Pavlovian law of strength, by displaying a positive relationship between the duration of water immersion in training and the taste aversion observed in subsequent testing. Experiment 3 revealed that swimming rather than being wet is the critical agent, because a water shower did not endow rats with taste aversion. Experiment 4 found that taste aversion was a positive function of water level of the pools in training (0, 12 or 32 cm). These results, taken together, suggest that energy expenditure caused by physical exercise might be involved in the development of taste aversion.

Taste-aversion learning produced by combined treatment with subthreshold radiation and lithium chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1987-01-01

These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste-aversion learning. The first experiment determined the threshold for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr or each other. The resultsmore » are discussed in terms of the implications of these findings for understanding the nature of the unconditional stimuli leading to the acquisition of a conditioned taste aversion.« less

Aversive Learning of Colored Lights in Walking Honeybees

PubMed Central

Kirkerud, Nicholas H.; Schlegel, Ulrike; Giovanni Galizia, C.

2017-01-01

The honeybee has been established as an important model organism in studies on visual learning. So far the emphasis has been on appetitive conditioning, simulating floral discrimination, and homing behavior, where bees perform exceptionally well in visual discrimination tasks. However, bees in the wild also face dangers, and recent findings suggest that what is learned about visual percepts is highly context dependent. A stimulus that follows an unpleasant period, is associated with the feeling of relief- or safety in humans and animals, thus acquiring a positive meaning. Whether this is also the case in honeybees is still an open question. Here, we conditioned bees aversively in a walking arena where each half was illuminated by light of a specific wavelength and intensity, one of which was combined with electric shocks. In this paradigm, the bees' preferences to the different lights were modified through nine conditioning trials, forming robust escape, and avoidance behaviors. Strikingly, we found that while 465 nm (human blue) and 590 nm (human yellow) lights both could acquire negative valences (inducing avoidance response), 525 nm (human green) light could not. This indicates that green light holds an innate meaning of safety which is difficult to overrule even through intensive aversive conditioning. The bees had slight initial preferences to green over the blue and the yellow lights, which could be compensated by adjusting light intensity. However, this initial bias played a minor role while the chromatic properties were the most salient characteristics of the light stimuli during aversive conditioning. Moreover, bees could learn the light signaling safety, revealing the existence of a relief component in aversive operant conditioning, similar to what has been observed in other animals. PMID:28588460

Genotype modulates age-related alterations in sensitivity to the aversive effects of ethanol: an eight inbred strain analysis of conditioned taste aversion.

PubMed

Moore, E M; Forrest, R D; Boehm, S L

2013-02-01

Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Currently there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in eight inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T(+) tf/J, C3H/HeJ and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1 h. Immediately following access mice were administered ethanol (0, 1.5, 2.25 and 3 g/kg, ip). This procedure was repeated in 72 h intervals for a total of five CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Systemic 5-Bromo-2-Deoxyuridine Induces Conditioned Flavor Aversion and C-Fos in the Visceral Neuraxis

ERIC Educational Resources Information Center

Kimbrough, Adam; Kwon, Bumsup; Eckel, Lisa A.; Houpt, Thomas A.

2011-01-01

5-bromo-2-deoxyuridine (BrdU) is often used in studies of adult neurogenesis and olfactory learning, but it can also have toxic effects on highly proliferative tissue. We found that pairing Kool-Aid flavors with acute systemic injections of BrdU induced strong conditioned flavor aversions. Intermittent injections during Kool-Aid-glucose…

Forward conditioning with wheel running causes place aversion in rats.

PubMed

Masaki, Takahisa; Nakajima, Sadahiko

2008-09-01

Backward pairings of a distinctive chamber as a conditioned stimulus and wheel running as an unconditioned stimulus (i.e., running-then-chamber) can produce a conditioned place preference in rats. The present study explored whether a forward conditioning procedure with these stimuli (i.e., chamber-then-running) would yield place preference or aversion. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, but confinement in the other was not. After four repetitions of this treatment (i.e., differential conditioning), a choice preference test was given in which the rat had free access to both chambers. This choice test showed that the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, a 60-min running opportunity after confinement in a distinctive chamber caused conditioned aversion to that chamber after four paired trials. This result was discussed with regard to the opponent-process theory of motivation.

Neural Correlates of Decision-Making Under Ambiguity and Conflict.

PubMed

Pushkarskaya, Helen; Smithson, Michael; Joseph, Jane E; Corbly, Christine; Levy, Ifat

2015-01-01

HIGHLIGHTS We use a simple gambles design in an fMRI study to compare two conditions: ambiguity and conflict.Participants were more conflict averse than ambiguity averse.Ambiguity aversion did not correlate with conflict aversion.Activation in the medial prefrontal cortex correlated with ambiguity level and ambiguity aversion.Activation in the ventral striatum correlated with conflict level and conflict aversion. Studies of decision making under uncertainty generally focus on imprecise information about outcome probabilities ("ambiguity"). It is not clear, however, whether conflicting information about outcome probabilities affects decision making in the same manner as ambiguity does. Here we combine functional magnetic resonance imaging (fMRI) and a simple gamble design to study this question. In this design the levels of ambiguity and conflict are parametrically varied, and ambiguity and conflict gambles are matched on expected value. Behaviorally, participants avoided conflict more than ambiguity, and attitudes toward ambiguity and conflict did not correlate across participants. Neurally, regional brain activation was differentially modulated by ambiguity level and aversion to ambiguity and by conflict level and aversion to conflict. Activation in the medial prefrontal cortex was correlated with the level of ambiguity and with ambiguity aversion, whereas activation in the ventral striatum was correlated with the level of conflict and with conflict aversion. These novel results indicate that decision makers process imprecise and conflicting information differently, a finding that has important implications for basic and clinical research.

Neural Correlates of Decision-Making Under Ambiguity and Conflict

PubMed Central

Pushkarskaya, Helen; Smithson, Michael; Joseph, Jane E.; Corbly, Christine; Levy, Ifat

2015-01-01

HIGHLIGHTS We use a simple gambles design in an fMRI study to compare two conditions: ambiguity and conflict.Participants were more conflict averse than ambiguity averse.Ambiguity aversion did not correlate with conflict aversion.Activation in the medial prefrontal cortex correlated with ambiguity level and ambiguity aversion.Activation in the ventral striatum correlated with conflict level and conflict aversion. Studies of decision making under uncertainty generally focus on imprecise information about outcome probabilities (“ambiguity”). It is not clear, however, whether conflicting information about outcome probabilities affects decision making in the same manner as ambiguity does. Here we combine functional magnetic resonance imaging (fMRI) and a simple gamble design to study this question. In this design the levels of ambiguity and conflict are parametrically varied, and ambiguity and conflict gambles are matched on expected value. Behaviorally, participants avoided conflict more than ambiguity, and attitudes toward ambiguity and conflict did not correlate across participants. Neurally, regional brain activation was differentially modulated by ambiguity level and aversion to ambiguity and by conflict level and aversion to conflict. Activation in the medial prefrontal cortex was correlated with the level of ambiguity and with ambiguity aversion, whereas activation in the ventral striatum was correlated with the level of conflict and with conflict aversion. These novel results indicate that decision makers process imprecise and conflicting information differently, a finding that has important implications for basic and clinical research. PMID:26640434

Playing it safe but losing anyway – serotonergic signaling of aversive outcomes in dorsomedial prefrontal cortex in the context of risk-aversion

PubMed Central

Macoveanu, Julian; Rowe, James B; Hornboll, Bettina; Elliott, Rebecca; Paulson, Olaf B; Knudsen, Gitte M; Siebner, Hartwig R

2015-01-01

Risk avoidance is an important determinant of human behavior. The neurotransmitter serotonin has long been implicated in processing aversive outcomes caused by risky decisions. However, it is unclear whether serotonin provides a neurobiological link between making a risk aversive decision and the response to an aversive outcome. Using pharmacological fMRI, we manipulated the availability of serotonin in healthy volunteers while performing a gambling task. The same group of participants was studied in three fMRI sessions: (i) during intravenous administration of the SSRI citalopram to increase the serotonergic tone, (ii) after acute tryptophan depletion (ATD) to reduce central serotonin levels, or (iii) without interventions. ATD and citalopran had opposite effects on outcome related activity in dorsomedial prefrontal cortex (dmPFC) and amygdala. Relative to the control condition, ATD increased and citalopram decreased the neural response to aversive outcomes in dmPFC. Conversely, ATD decreased and citalopram increased the neural response to aversive outcomes in left amygdala. Critically, these pharmacological effects were restricted to aversive outcomes that were caused by low-risk decision and led to a high missed reward. ATD and citalopram did not alter the neural response to positive outcomes in dmPFC, but relative to ATD, citalopram produced a bilateral increase in the amygdala response to large wins caused by high-risk choices. The results show a selective involvement of the serotonergic system in neocortical processing of aversive outcomes resulting from risk-averse decisions, thereby linking risk aversion and processing of aversive outcomes in goal-directed behaviors. PMID:23051938

Lesions of the medial prefrontal cortex cause maladaptive sexual behavior in male rats.

PubMed

Davis, Jon F; Loos, Maarten; Di Sebastiano, Andrea R; Brown, Jennifer L; Lehman, Michael N; Coolen, Lique M

2010-06-15

An inability to inhibit behaviors once they become maladaptive is a component of several psychiatric illnesses, and the medial prefrontal cortex (mPFC) was identified as a potential mediator of behavioral inhibition. The current study tested if the mPFC is involved in inhibition of sexual behavior when associated with aversive outcomes. Using male rats, effects of lesions of the infralimbic and prelimbic areas of the mPFC on expression of sexual behavior and ability to inhibit mating were tested using a paradigm of copulation-contingent aversion. Medial prefrontal cortex lesions did not alter expression of sexual behavior. In contrast, mPFC lesions completely blocked the acquisition of sex-aversion conditioning and lesioned animals continued to mate, in contrast to the robust behavioral inhibition toward copulation in mPFC intact male animals, resulting in only 22% of intact male animals continuing to mate. However, rats with mPFC lesions were capable of forming a conditioned place preference to sexual reward and conditioned place aversion for lithium chloride, suggesting that these lesions did not alter associative learning or sensitivity for lithium chloride. The current study indicates that animals with mPFC lesions are likely capable of forming the associations with aversive outcomes of their behavior but lack the ability to suppress seeking of sexual reward in the face of aversive consequences. These data may contribute to a better understanding of a common pathology underlying impulse control disorders, as compulsive sexual behavior has a high prevalence of comorbidity with psychiatric disorders and Parkinson's disease.

Sweet and bitter taste of ethanol in C57BL/6J and DBA2/J mouse strains.

PubMed

Blizard, David A

2007-01-01

Studies of inbred strains of rats and mice have suggested a positive association between strain variations in sweet taste and ethanol intake. However, strain associations by themselves are insufficient to support a functional link between taste and ethanol intake. We used conditioned taste aversion (CTA) to explore the sweet and bitter taste of ethanol and ability to detect sucrose, quinine and ethanol in C57BL/6J (B6) and DBA/2J (D2) mouse strains that are frequently used in alcohol research. The present study showed that C57BL/6J mice generalized taste aversions from sucrose and quinine solutions to 10% ethanol and, reciprocally, aversions to 10% ethanol generalized to each of these solutions presented separately. Only conditioned aversions to quinine generalized to ethanol in the DBA/2J strain but an aversion conditioned to ethanol did not generalize reciprocally to quinine. Thus, considering these two gustatory qualities, 10% ethanol tastes both sweet and bitter to B6 mice but only bitter to D2. Both strains were able to generalize taste aversions across different concentrations of the same compound. B6 were able to detect lower concentrations of quinine than D2 but both strains were able to detect sucrose and (in contrast to previous findings) ethanol at similar concentrations. The strain-dependent gustatory profiles for ethanol may make an important contribution to the understanding of the undoubtedly complex mechanisms influencing high ethanol preference of B6 and pronounced ethanol avoidance of D2 mice.

Conditioned taste aversion to ethanol in a social context: impact of age and sex.

PubMed

Morales, Melissa; Schatz, Kelcie C; Anderson, Rachel I; Spear, Linda P; Varlinskaya, Elena I

2014-03-15

Given that human adolescents place a high value on social interactions-particularly while consuming alcohol-the current study utilized a novel social drinking paradigm to examine rewarding and aversive properties of ethanol in non-water deprived rats that were housed and tested in groups of five same-sex littermates. On postnatal day P34 (adolescents) or P69 (adults), rats were habituated to the testing apparatus for 30 min. On the next day, animals were placed into the test apparatus and given 30 min access to a supersaccharin solution (3% sucrose; 0.125% saccharin), followed immediately by an intraperitoneal injection of ethanol (0, 0.25, 0.5, 1.0, 1.5 g/kg). Subsequent intake of the supersacharrin solution was assessed on three consecutive test days. Adolescent males were less sensitive to ethanol's aversive effects than adult males, with adolescent males maintaining an aversion on all three test days only at the 1.5 g/kg dose, whereas adults demonstrated aversions across test days to 1 and 1.5 g/kg. Adolescent females maintained aversions to 1 and 1.5 g/kg across days, whereas adult females continued to show an aversion to the 1.5 g/kg dose only. These opposite patterns of sensitivity that emerged among males and females at each age in the propensity to maintain an ethanol-induced taste aversion under social conditions may contribute to age- and sex-related differences in ethanol intake. Testing in social groups may be useful for future work when studying rodent models of adolescent alcohol use given the importance that human adolescents place on drinking in social settings. Copyright © 2014 Elsevier B.V. All rights reserved.

Anticipation of high arousal aversive and positive movie clips engages common and distinct neural substrates

PubMed Central

Carlson, Joshua M.; Rubin, Denis; Cha, Jiook; Mujica-Parodi, Lilianne

2015-01-01

The neural correlates of anxious anticipation have been primarily studied with aversive and neutral stimuli. In this study, we examined the effect of valence on anticipation by using high arousal aversive and positive stimuli and a condition of uncertainty (i.e. either positive or aversive). The task consisted of predetermined cues warning participants of upcoming aversive, positive, ‘uncertain’ (either aversive or positive) and neutral movie clips. Anticipation of all affective clips engaged common regions including the anterior insula, dorsal anterior cingulate cortex, thalamus, caudate, inferior parietal and prefrontal cortex that are associated with emotional experience, sustained attention and appraisal. In contrast, the nucleus accumbens and medial prefrontal cortex, regions implicated in reward processing, were selectively engaged during anticipation of positive clips (depicting sexually explicit content) and the mid-insula, which has been linked to processing aversive stimuli, was selectively engaged during anticipation of aversive clips (depicting graphic medical procedures); these three areas were also activated during anticipation of ‘uncertain’ clips reflecting a broad preparatory response for both aversive and positive stimuli. These results suggest that a common circuitry is recruited in anticipation of affective clips regardless of valence, with additional areas preferentially engaged depending on whether expected stimuli are negative or positive. PMID:24984958

Ethanol-Induced Effects on Sting Extension Response and Punishment Learning in the Western Honey Bee (Apis mellifera)

PubMed Central

Giannoni-Guzmán, Manuel A.; Giray, Tugrul; Agosto-Rivera, Jose Luis; Stevison, Blake K.; Freeman, Brett; Ricci, Paige; Brown, Erika A.; Abramson, Charles I.

2014-01-01

Acute ethanol administration is associated with sedation and analgesia as well as behavioral disinhibition and memory loss but the mechanisms underlying these effects remain to be elucidated. During the past decade, insects have emerged as important model systems to understand the neural and genetic bases of alcohol effects. However, novel assays to assess ethanol's effects on complex behaviors in social or isolated contexts are necessary. Here we used the honey bee as an especially relevant model system since bees are typically exposed to ethanol in nature when collecting standing nectar crop of flowers, and there is recent evidence for independent biological significance of this exposure for social behavior. Bee's inhibitory control of the sting extension response (SER) and a conditioned-place aversion assay were used to study ethanol effects on analgesia, behavioral disinhibition, and associative learning. Our findings indicate that although ethanol, in a dose-dependent manner, increases SER thresholds (analgesic effects), it disrupts the ability of honey bees to inhibit SER and to associate aversive stimuli with their environment. These results suggest that ethanol's effects on analgesia, behavioral disinhibition and associative learning are common across vertebrates and invertebrates. These results add to the use of honey bees as an ethanol model to understand ethanol's effects on complex, socially relevant behaviors. PMID:24988309

Motivational state controls the prediction error in Pavlovian appetitive-aversive interactions.

PubMed

Laurent, Vincent; Balleine, Bernard W; Westbrook, R Frederick

2018-01-01

Contemporary theories of learning emphasize the role of a prediction error signal in driving learning, but the nature of this signal remains hotly debated. Here, we used Pavlovian conditioning in rats to investigate whether primary motivational and emotional states interact to control prediction error. We initially generated cues that positively or negatively predicted an appetitive food outcome. We then assessed how these cues modulated aversive conditioning when a novel cue was paired with a foot shock. We found that a positive predictor of food enhances, whereas a negative predictor of that same food impairs, aversive conditioning. Critically, we also showed that the enhancement produced by the positive predictor is removed by reducing the value of its associated food. In contrast, the impairment triggered by the negative predictor remains insensitive to devaluation of its associated food. These findings provide compelling evidence that the motivational value attributed to a predicted food outcome can directly control appetitive-aversive interactions and, therefore, that motivational processes can modulate emotional processes to generate the final error term on which subsequent learning is based. Copyright © 2017 Elsevier Inc. All rights reserved.

Does ambiguity aversion influence the framing effect during decision making?

PubMed

Osmont, Anaïs; Cassotti, Mathieu; Agogué, Marine; Houdé, Olivier; Moutier, Sylvain

2015-04-01

Decision-makers present a systematic tendency to avoid ambiguous options for which the level of risk is unknown. This ambiguity aversion is one of the most striking decision-making biases. Given that human choices strongly depend on the options' presentation, the purpose of the present study was to examine whether ambiguity aversion influences the framing effect during decision making. We designed a new financial decision-making task involving the manipulation of both frame and uncertainty levels. Thirty-seven participants had to choose between a sure option and a gamble depicting either clear or ambiguous probabilities. The results revealed a clear preference for the sure option in the ambiguity condition regardless of frame. However, participants presented a framing effect in both the risk and ambiguity conditions. Indeed, the framing effect was bidirectional in the risk condition and unidirectional in the ambiguity condition given that it did not involve preference reversal but only a more extreme choice tendency.

Aversive workplace conditions and absenteeism: taking referent group norms and supervisor support into account.

PubMed

Biron, Michal; Bamberger, Peter

2012-07-01

Past research reveals inconsistent findings regarding the association between aversive workplace conditions and absenteeism, suggesting that other, contextual factors may play a role in this association. Extending contemporary models of absence, we draw from the social identity theory of attitude-behavior relations to examine how peer absence-related norms and leader support combine to explain the effect of aversive workplace conditions on absenteeism. Using a prospective design and a random sample of transit workers, we obtained results indicating that perceived job hazards and exposure to critical incidents are positively related to subsequent absenteeism, but only under conditions of more permissive peer absence norms. Moreover, this positive impact of peer norms on absenteeism is amplified among employees perceiving their supervisor to be less supportive and is attenuated to the point of nonsignificance among those viewing their supervisor as more supportive. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Interacting Brain Systems Modulate Memory Consolidation

PubMed Central

McIntyre, Christa K.; McGaugh, James L.; Williams, Cedric L.

2011-01-01

Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID:22085800

C. elegans positive butanone learning, short-term, and long-term associative memory assays.

PubMed

Kauffman, Amanda; Parsons, Lance; Stein, Geneva; Wills, Airon; Kaletsky, Rachel; Murphy, Coleen

2011-03-11

The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans navigates its environment through neuron-specific detection of food and chemical odors, and can associate nutritive states with chemical odors, temperature, and the pathogenicity of a food source. Here, we describe assays of C. elegans associative learning and short- and long-term associative memory. We modified an aversive olfactory learning paradigm to instead produce a positive response; the assay involves starving ~400 worms, then feeding the worms in the presence of the AWC neuron-sensed volatile chemoattractant butanone at a concentration that elicits a low chemotactic index (similar to Toroyama et al.). A standard population chemotaxis assay1 tests the worms' attraction to the odorant immediately or minutes to hours after conditioning. After conditioning, wild-type animals' chemotaxis to butanone increases ~0.6 Chemotaxis Index units, its "Learning Index". Associative learning is dependent on the presence of both food and butanone during training. Pairing food and butanone for a single conditioning period ("massed training") produces short-term associative memory that lasts ~2 hours. Multiple conditioning periods with rest periods between ("spaced training") yields long-term associative memory (<40 hours), and is dependent on the cAMP Response Element Binding protein (CREB), a transcription factor required for long-term memory across species. Our protocol also includes image analysis methods for quick and accurate determination of chemotaxis indices. High-contrast images of animals on chemotaxis assay plates are captured and analyzed by worm counting software in MatLab. The software corrects for uneven background using a morphological tophat transformation. Otsu's method is then used to determine a threshold to separate worms from the background. Very small particles are removed automatically and larger non-worm regions (plate edges or agar punches) are removed by manual selection. The software then estimates the size of single worm by ignoring regions that are above a specified maximum size and taking the median size of the remaining regions. The number of worms is then estimated by dividing the total area identified as occupied by worms by the estimated size of a single worm. We have found that learning and short- and long-term memory can be distinguished, and that these processes share similar key molecules with higher organisms. Our assays can quickly test novel candidate genes or molecules that affect learning and short- or long-term memory in C. elegans that are relevant across species.

Investigating the Predictive Value of Functional MRI to Appetitive and Aversive Stimuli: A Pattern Classification Approach

PubMed Central

McCabe, Ciara; Rocha-Rego, Vanessa

2016-01-01

Background Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. Method 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. Results The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Conclusions Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder. PMID:27870866

Increased levels of conditioned fear and avoidance behavior coincide with changes in phosphorylation of the protein kinase B (AKT) within the amygdala in a mouse model of extremes in trait anxiety.

PubMed

Yen, Yi-Chun; Mauch, Christoph P; Dahlhoff, Maik; Micale, Vincenzo; Bunck, Mirjam; Sartori, Simone B; Singewald, Nicolas; Landgraf, Rainer; Wotjak, Carsten T

2012-07-01

Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned fear. To gain further insights into the mechanisms underlying these phenomenona, we studied conditioned fear in mice originating form a bi-directional selective breeding approach, which is based on elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxiety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the basolateral amygdala 45 min after conditioning. No similar changes were observed after non-associative immediate shock presentations. Fear extinction of recent but not older fear memories was preserved. However, HAB mice were more prone to relapse of conditioned fear with the passage of time. HAB mice also displayed higher levels of contextual fear compared to NAB and LAB mice and exaggerated avoidance following step-down avoidance training. Interestingly, HAB mice showed lower and LAB mice higher levels of acoustic startle responses compared to NAB controls. The increase in arousal observed in LAB mice coincided with the general absence of conditioned freezing. Taken together, our results suggest that the genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic memories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking behavior seems to be associated with an increase in active coping styles. Our data imply changes in AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories. Copyright © 2012 Elsevier Inc. All rights reserved.

Hedonic and Nucleus Accumbens Neural Responses to a Natural Reward Are Regulated by Aversive Conditioning

ERIC Educational Resources Information Center

Roitman, Mitchell F.; Wheeler, Robert A.; Tiesinga, Paul H. E.; Roitman, Jamie D.; Carelli, Regina M.

2010-01-01

The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli. Learning can alter the hedonic valence of a given stimulus, and it remains unclear how the NAc encodes this shift. The present study examined whether the population response of NAc neurons to a taste stimulus is plastic using a conditioned taste aversion (CTA)…

Extinction of Conditioned Taste Aversion Depends on Functional Protein Synthesis but Not on NMDA Receptor Activation in the Ventromedial Prefrontal Cortex

ERIC Educational Resources Information Center

Akirav, Irit; Khatsrinov, Vicktoria; Vouimba, Rose-Marie; Merhav, Maayan; Ferreira, Guillaume; Rosenblum, Kobi; Maroun, Mouna

2006-01-01

We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin,…

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

PubMed

Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

2017-02-15

The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Relapse of Extinguished Fear after Exposure to a Dangerous Context Is Mitigated by Testing in a Safe Context

ERIC Educational Resources Information Center

Goode, Travis D.; Kim, Janice J.; Maren, Stephen

2015-01-01

Aversive events can trigger relapse of extinguished fear memories, presenting a major challenge to the long-term efficacy of therapeutic interventions. Here, we examined factors regulating the relapse of extinguished fear after exposure of rats to a dangerous context. Rats received unsignaled shock in a distinct context ("dangerous"…

Unpacking buyer-seller differences in valuation from experience: A cognitive modeling approach.

PubMed

Pachur, Thorsten; Scheibehenne, Benjamin

2017-12-01

People often indicate a higher price for an object when they own it (i.e., as sellers) than when they do not (i.e., as buyers)-a phenomenon known as the endowment effect. We develop a cognitive modeling approach to formalize, disentangle, and compare alternative psychological accounts (e.g., loss aversion, loss attention, strategic misrepresentation) of such buyer-seller differences in pricing decisions of monetary lotteries. To also be able to test possible buyer-seller differences in memory and learning, we study pricing decisions from experience, obtained with the sampling paradigm, where people learn about a lottery's payoff distribution from sequential sampling. We first formalize different accounts as models within three computational frameworks (reinforcement learning, instance-based learning theory, and cumulative prospect theory), and then fit the models to empirical selling and buying prices. In Study 1 (a reanalysis of published data with hypothetical decisions), models assuming buyer-seller differences in response bias (implementing a strategic-misrepresentation account) performed best; models assuming buyer-seller differences in choice sensitivity or memory (implementing a loss-attention account) generally fared worst. In a new experiment involving incentivized decisions (Study 2), models assuming buyer-seller differences in both outcome sensitivity (as proposed by a loss-aversion account) and response bias performed best. In both Study 1 and 2, the models implemented in cumulative prospect theory performed best. Model recovery studies validated our cognitive modeling approach, showing that the models can be distinguished rather well. In summary, our analysis supports a loss-aversion account of the endowment effect, but also reveals a substantial contribution of simple response bias.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

PubMed

Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Ceretta, Renan A; Dominguini, Diogo; Ferrari, Pâmela; Gubert, Carolina; Jornada, Luciano K; Budni, Josiane; Kapczinski, Flávio; Quevedo, João

2014-10-01

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis. © 2014 by the Society for Experimental Biology and Medicine.

PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

PubMed Central

Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.

2012-01-01

Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30–45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. PMID:22698870

Delta-9-tetrahydrocannabinol (THC) history fails to affect THC's ability to induce place preferences in rats.

PubMed

Hempel, Briana J; Wakeford, Alison G P; Clasen, Matthew M; Friar, Mary A; Riley, Anthony L

2016-05-01

In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats. The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg). THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC. The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of the hypothalamic-pituitary-adrenal axis in lithium-induced conditioned taste aversion learning.

PubMed

Jahng, Jeong Won; Lee, Jong-Ho

2015-12-05

Intraperitoneal injections (ip) of lithium chloride at large doses induce c-Fos expression in the brain regions implicated in conditioned taste aversion (CTA) learning, and also activate the hypothalamic-pituitary-adrenal (HPA) axis and increase the plasma corticosterone levels in rats. A pharmacologic treatment blunting the lithium-induced c-Fos expression in the brain regions, but not the HPA axis activation, induced CTA formation. Synthetic glucocorticoids at conditioning, but not glucocorticoid antagonist, attenuated the lithium-induced CTA acquisition. The CTA acquisition by ip lithium was not affected by adrenalectomy regardless of basal corticosterone supplement, but the extinction was delayed in the absence of basal corticosterone. Glucocorticoids overloading delayed the extinction memory formation of lithium-induced CTA. ip lithium consistently induced the brain c-Fos expression, the HPA activation and CTA formation regardless of the circadian activation of the HPA axis. Intracerebroventricular (icv) injections of lithium at day time also increased the brain c-Fos expression, activated the HPA axis and induced CTA acquisition. However, icv lithium at night, when the HPA axis shows its circadian activation, did not induce CTA acquisition nor activate the HPA axis, although it increased the brain c-Fos expression. These results suggest that the circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA learning in rats, and the HPA axis activation may be necessary for the central effect of lithium in CTA formation. Also, glucocorticoids may be required for a better extinction; however, increased glucocorticoids hinder both the acquisition and the extinction of lithium-induced CTA. Copyright © 2015. Published by Elsevier B.V.

Midbrain dopamine neurons signal aversion in a reward-context-dependent manner

PubMed Central

Matsumoto, Hideyuki; Tian, Ju; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2016-01-01

Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons’ responses to reward and punishment. When a single odor predicted both reward and punishment, dopamine neurons’ responses to that odor reflected the integrated value of both outcomes. Thus, in low reward contexts, dopamine neurons signal value prediction errors (VPEs) integrating information about both reward and aversion in a common currency. In contrast, in high reward contexts, dopamine neurons acquired a short-latency excitation to aversive events that masked their VPE signaling. Our results demonstrate the importance of considering the contexts to examine the representation in dopamine neurons and uncover different modes of dopamine signaling, each of which may be adaptive for different environments. DOI: http://dx.doi.org/10.7554/eLife.17328.001 PMID:27760002

Role of the area postrema in radiation-induced taste aversion learning and emesis in cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Chedester, A.L.

1986-01-01

The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved inmore » the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.« less

Taste aversion learning produced by combined treatment with subthreshold radiation and lithium chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1987-08-01

These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride didmore » produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.« less

Taste aversion learning produced by combined treatment with subthreshold radiation and lithium chloride.

PubMed

Rabin, B M; Hunt, W A; Lee, J

1987-08-01

These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.

Anticipation of high arousal aversive and positive movie clips engages common and distinct neural substrates.

PubMed

Greenberg, Tsafrir; Carlson, Joshua M; Rubin, Denis; Cha, Jiook; Mujica-Parodi, Lilianne

2015-04-01

The neural correlates of anxious anticipation have been primarily studied with aversive and neutral stimuli. In this study, we examined the effect of valence on anticipation by using high arousal aversive and positive stimuli and a condition of uncertainty (i.e. either positive or aversive). The task consisted of predetermined cues warning participants of upcoming aversive, positive, 'uncertain' (either aversive or positive) and neutral movie clips. Anticipation of all affective clips engaged common regions including the anterior insula, dorsal anterior cingulate cortex, thalamus, caudate, inferior parietal and prefrontal cortex that are associated with emotional experience, sustained attention and appraisal. In contrast, the nucleus accumbens and medial prefrontal cortex, regions implicated in reward processing, were selectively engaged during anticipation of positive clips (depicting sexually explicit content) and the mid-insula, which has been linked to processing aversive stimuli, was selectively engaged during anticipation of aversive clips (depicting graphic medical procedures); these three areas were also activated during anticipation of 'uncertain' clips reflecting a broad preparatory response for both aversive and positive stimuli. These results suggest that a common circuitry is recruited in anticipation of affective clips regardless of valence, with additional areas preferentially engaged depending on whether expected stimuli are negative or positive. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.