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J. Van Honk - One of the best experts on this subject based on the ideXlab platform.
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the human Basolateral Amygdala is indispensable for social experiential learning
Current Biology, 2019Co-Authors: Lisa A Rosenberger, David Terburg, Dan J. Stein, J. Van Honk, Christoph Eisenegger, Michael Naef, Jorique FourieAbstract:Summary Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [ 1 ]. We learn about others’ trustworthiness through trial and error during repeated interactions [ 2 ]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the Basolateral Amygdala (BLA) in social experiential learning [ 3 , 4 ]. The human BLA has undergone a reorganization with massive expansion relative to other Amygdala nuclei [ 5 ], and there is no translational research on its role in experiential learning. The human Amygdala is traditionally researched as a single structure [ 6 ], neglecting the sub-nuclei’s structural und functional differences [ 7 ], which might explain inconsistent findings in research on social interactions [ 8 , 9 ]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning.
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translational neuroscience of Basolateral Amygdala lesions studies of urbach wiethe disease
Journal of Neuroscience Research, 2016Co-Authors: N. Koen, David Terburg, Barak Morgan, Dan J. Stein, J. Fourie, Ron Stoop, J. Van HonkAbstract:Urbach-Wiethe disease (UWD) is an extremely rare autosomal recessive disorder characterized by mutations in the extracellular matrix protein 1 gene on chromosome 1. Typical clinical manifestations include voice hoarseness in early infancy and neuropsychiatric, laryngeal, and dermatological pathologies later in life. Neuroimaging studies have revealed a pattern of brain calcification often but not exclusively leading to selective bilateral Amygdala damage. A large body of work on Amygdala lesions in rodents exists, generally employing a subregion model focused on the Basolateral Amygdala (BLA) and the central-medial Amygdala. However, human work usually considers the Amygdala as a unified structure, not only complicating the translation of animal findings to humans but also providing a unique opportunity for further research. To compare data from rodent models with human cases and to complement existing data from Europe and North America, a series of investigations was undertaken on UWD subjects with selective BLA damage in the Namaqualand region, South Africa. This review presents key findings from this work, including fear processing, social-economic behavior, and emotional conflict processing. Our findings are broadly consistent with and support rodent models of selective BLA lesions and show that the BLA is integral to processing sensory stimuli and exhibits inhibitory regulation of responses to unconditioned innate fear stimuli. Furthermore, our findings suggest that the human BLA mediates calculative-instrumental economic behaviors and may compromise working memory via competition for attentional resources between the BLA salience detection system and the dorsolateral prefrontal cortex working memory system.
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impaired acquisition of classically conditioned fear potentiated startle reflexes in humans with focal bilateral Basolateral Amygdala damage
Social Cognitive and Affective Neuroscience, 2015Co-Authors: David Terburg, Barak Morgan, Dan J. Stein, J. Van Honk, Floris KlumpersAbstract:Based on studies in rodents, the Basolateral Amygdala (BLA) is considered a key site for experience-dependent neural plasticity underlying the acquisition of conditioned fear responses. In humans, very few studies exist of subjects with selective Amygdala lesions and those studies have only implicated the Amygdala more broadly leaving the role of Amygdala sub-regions underexplored. We tested a rare sample of subjects (N ¼ 4) with unprecedented focal bilateral BLA lesions due to a genetic condition called Urbach–Wiethe disease. In a classical delay fear conditioning experiment, these subjects showed impaired acquisition of conditioned fear relative to a group of matched control subjects (N ¼ 10) as measured by fear-potentiation of the defensive eye-blink startle reflex. After the experiment, the BLA-damaged cases showed normal declarative memory of the conditioned association. Our findings provide new evidence that the human BLA is essential to drive fast classically conditioned defensive reflexes.
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generous economic investments after Basolateral Amygdala damage
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: J. Van Honk, David Terburg, Dan J. Stein, Christoph Eisenegger, Barak MorganAbstract:Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The Amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the Basolateral Amygdala (BLA) subserves instrumental behaviors and regulates the central-medial Amygdala, which subserves impulsive behaviors. The human Amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial Amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.
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Paradoxical facilitation of working memory after Basolateral Amygdala damage.
Public Library of Science (PLoS), 2026Co-Authors: Barak Morgan, David Terburg, Helena B Thornton, Dan J. Stein, J. Van HonkAbstract:Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up Amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the Amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which Amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral Basolateral Amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective Basolateral Amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining Amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical functional facilitation effect
David Terburg - One of the best experts on this subject based on the ideXlab platform.
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the human Basolateral Amygdala is indispensable for social experiential learning
Current Biology, 2019Co-Authors: Lisa A Rosenberger, David Terburg, Dan J. Stein, J. Van Honk, Christoph Eisenegger, Michael Naef, Jorique FourieAbstract:Summary Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [ 1 ]. We learn about others’ trustworthiness through trial and error during repeated interactions [ 2 ]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the Basolateral Amygdala (BLA) in social experiential learning [ 3 , 4 ]. The human BLA has undergone a reorganization with massive expansion relative to other Amygdala nuclei [ 5 ], and there is no translational research on its role in experiential learning. The human Amygdala is traditionally researched as a single structure [ 6 ], neglecting the sub-nuclei’s structural und functional differences [ 7 ], which might explain inconsistent findings in research on social interactions [ 8 , 9 ]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning.
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the Basolateral Amygdala is essential for rapid escape a human and rodent study
Cell, 2018Co-Authors: David Terburg, Barak Morgan, Estrella R Montoya, Floris Klumpers, Diego Scheggia, Rodrigo Trianadel Rio, Alexandru Cristian Ciobanu, Peter A Bos, Gion GiobellinaAbstract:Rodent research delineates how the Basolateral Amygdala (BLA) and central Amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species, an essential role for the BLA in the selection of active escape over passive freezing during exposure to imminent yet escapable threat (Timm). In response to Timm, BLA-damaged humans showed increased startle potentiation and BLA-silenced rats demonstrated increased startle potentiation, freezing, and reduced escape behavior as compared to controls. Neuroimaging in humans suggested that the BLA reduces passive defensive responses by inhibiting the brainstem via the CeA. Indeed, Timm conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient Timm responses in BLA-silenced rats. Our data reveal how the BLA, via the CeA, adaptively regulates escape behavior from imminent threat and that this mechanism is evolutionary conserved across rodents and humans.
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translational neuroscience of Basolateral Amygdala lesions studies of urbach wiethe disease
Journal of Neuroscience Research, 2016Co-Authors: N. Koen, David Terburg, Barak Morgan, Dan J. Stein, J. Fourie, Ron Stoop, J. Van HonkAbstract:Urbach-Wiethe disease (UWD) is an extremely rare autosomal recessive disorder characterized by mutations in the extracellular matrix protein 1 gene on chromosome 1. Typical clinical manifestations include voice hoarseness in early infancy and neuropsychiatric, laryngeal, and dermatological pathologies later in life. Neuroimaging studies have revealed a pattern of brain calcification often but not exclusively leading to selective bilateral Amygdala damage. A large body of work on Amygdala lesions in rodents exists, generally employing a subregion model focused on the Basolateral Amygdala (BLA) and the central-medial Amygdala. However, human work usually considers the Amygdala as a unified structure, not only complicating the translation of animal findings to humans but also providing a unique opportunity for further research. To compare data from rodent models with human cases and to complement existing data from Europe and North America, a series of investigations was undertaken on UWD subjects with selective BLA damage in the Namaqualand region, South Africa. This review presents key findings from this work, including fear processing, social-economic behavior, and emotional conflict processing. Our findings are broadly consistent with and support rodent models of selective BLA lesions and show that the BLA is integral to processing sensory stimuli and exhibits inhibitory regulation of responses to unconditioned innate fear stimuli. Furthermore, our findings suggest that the human BLA mediates calculative-instrumental economic behaviors and may compromise working memory via competition for attentional resources between the BLA salience detection system and the dorsolateral prefrontal cortex working memory system.
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impaired acquisition of classically conditioned fear potentiated startle reflexes in humans with focal bilateral Basolateral Amygdala damage
Social Cognitive and Affective Neuroscience, 2015Co-Authors: David Terburg, Barak Morgan, Dan J. Stein, J. Van Honk, Floris KlumpersAbstract:Based on studies in rodents, the Basolateral Amygdala (BLA) is considered a key site for experience-dependent neural plasticity underlying the acquisition of conditioned fear responses. In humans, very few studies exist of subjects with selective Amygdala lesions and those studies have only implicated the Amygdala more broadly leaving the role of Amygdala sub-regions underexplored. We tested a rare sample of subjects (N ¼ 4) with unprecedented focal bilateral BLA lesions due to a genetic condition called Urbach–Wiethe disease. In a classical delay fear conditioning experiment, these subjects showed impaired acquisition of conditioned fear relative to a group of matched control subjects (N ¼ 10) as measured by fear-potentiation of the defensive eye-blink startle reflex. After the experiment, the BLA-damaged cases showed normal declarative memory of the conditioned association. Our findings provide new evidence that the human BLA is essential to drive fast classically conditioned defensive reflexes.
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generous economic investments after Basolateral Amygdala damage
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: J. Van Honk, David Terburg, Dan J. Stein, Christoph Eisenegger, Barak MorganAbstract:Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The Amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the Basolateral Amygdala (BLA) subserves instrumental behaviors and regulates the central-medial Amygdala, which subserves impulsive behaviors. The human Amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial Amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.
Michela Gallagher - One of the best experts on this subject based on the ideXlab platform.
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rapid associative encoding in Basolateral Amygdala depends on connections with orbitofrontal cortex
Neuron, 2005Co-Authors: Michael P Saddoris, Michela Gallagher, Geoffrey SchoenbaumAbstract:Certain goal-directed behaviors depend upon interactions between Basolateral Amygdala (ABL) and orbitofrontal cortex (OFC). Here we describe neurophysiological evidence of this cooperative function. We recorded from ABL in intact and OFC-lesioned rats during learning of odor discrimination problems and reversals. During learning, rats with ipsilateral OFC lesions exhibited a marked decline in the proportion of ABL neurons that fired differentially during cue sampling both before and after reversal and in the proportion of neurons that reversed odor preference when the odor-outcome associations were reversed. This decline appeared to reflect a loss of rapid flexibility in cue selectivity that characterized activity in intact rats. In addition, lesioned rats had fewer neurons that fired in anticipation of the predicted outcome during a delay period after responding but before outcome delivery. These findings support a role for OFC in facilitating the encoding of information about expected outcomes in ABL.
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rats with Basolateral Amygdala lesions show normal increases in conditioned stimulus processing but reduced conditioned potentiation of eating
Behavioral Neuroscience, 2001Co-Authors: Peter C Holland, Tammy Hatfield, Michela GallagherAbstract:Rats with neurotoxic lesions of Basolateral Amygdala (ABL) and control rats showed comparable enhancement of attentional processing of a visual stimulus when its predictive value was altered. In contrast, lesioned rats showed less potentiation of eating than did control rats when food was available during presentations of a conditioned stimulus that was previously paired with food. When considered together with previous data, these results indicate a double dissociation between effects of lesions of the ABL and of the Amygdala central nucleus on phenomena related to attentional processing and the acquisition of motivational value.
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neural encoding in orbitofrontal cortex and Basolateral Amygdala during olfactory discrimination learning
The Journal of Neuroscience, 1999Co-Authors: Geoffrey Schoenbaum, Andrea A Chiba, Michela GallagherAbstract:Orbitofrontal cortex (OFC) is part of a network of structures involved in adaptive behavior and decision making. Interconnections between OFC and Basolateral Amygdala (ABL) may be critical for encoding the motivational significance of stimuli used to guide behavior. Indeed, much research indicates that neurons in OFC and ABL fire selectively to cues based on their associative significance. In the current study recordings were made in each region within a behavioral paradigm that allowed comparison of the development of associative encoding over the course of learning. In each recording session, rats were presented with novel odors that were informative about the outcome of making a response and had to learn to withhold a response after sampling an odor that signaled a negative outcome. In some cases, reversal training was performed in the same session as the initial learning. Ninety-six of the 328 neurons recorded in OFC and 60 of the 229 neurons recorded in ABL exhibited selective activity during evaluation of the odor cues after learning had occurred. A substantial proportion of those neurons in ABL developed selective activity very early in training, and many reversed selectivity rapidly after reversal. In contrast, those neurons in OFC rarely exhibited selective activity during odor evaluation before the rats reached the criterion for learning, and far fewer reversed selectivity after reversal. The findings support a model in which ABL encodes the motivational significance of cues and OFC uses this information in the selection and execution of an appropriate behavioral strategy.
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orbitofrontal cortex and Basolateral Amygdala encode expected outcomes during learning
Nature Neuroscience, 1998Co-Authors: Geoffrey Schoenbaum, Andrea A Chiba, Michela GallagherAbstract:Reciprocal connections between the orbitofrontal cortex and the Basolateral nucleus of the Amygdala may provide a critical circuit for the learning that underlies goal-directed behavior. We examined neural activity in rat orbitofrontal cortex and Basolateral Amygdala during instrumental learning in an olfactory discrimination task. Neurons in both regions fired selectively during the anticipation of rewarding or aversive outcomes. This selective activity emerged early in training, before the rats had learned reliably to avoid the aversive outcome. The results support the concept that the Basolateral Amygdala and orbitofrontal cortex cooperate to encode information that may be used to guide goal-directed behavior.
Barry J Everitt - One of the best experts on this subject based on the ideXlab platform.
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The CB1 Receptor Antagonist AM251 Impairs Reconsolidation of Pavlovian Fear Memory in the Rat Basolateral Amygdala
Neuropsychopharmacology, 2014Co-Authors: Patrizia Ratano, Barry J Everitt, Amy L MiltonAbstract:We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the Basolateral Amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABA_A receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.
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differential roles of the prefrontal cortical subregions and Basolateral Amygdala in compulsive cocaine seeking and relapse after voluntary abstinence in rats
European Journal of Neuroscience, 2013Co-Authors: Yann Pelloux, Jennifer E Murray, Barry J EverittAbstract:Compulsive drug use and a persistent vulnerability to relapse are key features of addiction. Imaging studies have suggested that these features may result from deficits in prefrontal cortical structure and function, and thereby impaired top-down inhibitory control over limbic–striatal mechanisms of drug-seeking behaviour. We tested the hypothesis that selective damage to distinct subregions of the prefrontal cortex, or to the Amygdala, after a short history of cocaine taking would: (i) result in compulsive cocaine seeking at a time when it would not usually be displayed; or (ii) facilitate relapse to drug seeking after abstinence. Rats with selective, bilateral excitotoxic lesions of the Basolateral Amygdala or anterior cingulate, prelimbic, infralimbic, orbitofrontal or anterior insular cortices were trained to self-administer cocaine under a seeking–taking chained schedule. Intermittent mild footshock punishment of the cocaine-seeking response was then introduced. No prefrontal cortical lesion affected the ability of rats to withhold their seeking responses. However, rats with lesions to the Basolateral Amygdala increased their cocaine-seeking responses under punishment and were impaired in their acquisition of conditioned fear. Following a 7-day abstinence period, rats were re-exposed to the drug-seeking environment for assessment of relapse in the absence of punishment or cocaine. Rats with prelimbic cortex lesions showed decreased seeking responses during relapse, whereas those with anterior insular cortex lesions showed an increase. Combined, these results show that acute impairment of prefrontal cortical function does not result in compulsive cocaine seeking after a short history of self-administering cocaine, but further implicates subregions of the prefrontal cortex in relapse.
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The Basolateral Amygdala and nucleus accumbens core mediate dissociable aspects of drug memory reconsolidation.
Learn Mem, 2010Co-Authors: Florence R M Théberge, Amy L Milton, David Belin, Jonathan L C Lee, Barry J EverittAbstract:A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the Basolateral Amygdala in the reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intraBasolateral Amygdala zif268 ASO infusions at memory reactivation impaired the reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intraBasolateral Amygdala zif268 ASO infusions. These results suggest that both the Basolateral Amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where reconsolidation of a cue-drug memory occurs. However reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.
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excitotoxic lesions of the Basolateral Amygdala impair the acquisition of cocaine seeking behaviour under a second order schedule of reinforcement
Psychopharmacology, 1996Co-Authors: Rachel B Whitelaw, Trevor W. Robbins, Athina Markou, Barry J EverittAbstract:In these experiments we sought to establish the intravenous (IV) self-administration of cocaine under a second-order schedule of reinforcement in order: (i) to obtain reliable, drug-free levels of responding with cocaine as a reinforcer, and (ii) to enable investigation of the neural mechanisms by which arbitrary cues gain motivational salience and, as conditioned reinforcers, control over drug-seeking behaviour. Initially, each infusion of cocaine was made contingent upon a response on one of two identical levers and was paired with a 20-s light conditioned stimulus (CS). Responses on the second lever were recorded, but had no programmed consequence. When rats acquired stable rates of self-administration, a second-order schedule of the type FRx(FRy:S) was introduced, with values of “x” being increased progressively to 10 and then “y” from 2 through 8. Priming (i.e. non-contingent) infusions of cocaine were never given. Once the first infusion was obtained under the second-order schedule, further infusions were made contingent on each response (to a maximum of ten infusions/day). Each stage was repeated daily until the first infusion of each session was achieved within a 5-min criterion. Rats with bilateral, excitotoxic lesions of the Basolateral Amygdala readily acquired the IV self-administration of cocaine under a continuous reinforcement schedule, initially administering more infusions and maintaining a slightly elevated level of self-administration than controls. Despite increased numbers of CS/drug pairings, Basolateral Amygdala-lesioned rats were severely impaired in the acquisition of the second-order schedule of IV cocaine reinforcement. Lesioned rats showed a cocaine dose-response function that was shifted upwards relative to control subjects. There was no significant difference between drug-naive Amygdala-lesioned and control animals in the locomotor response to intraperitoneal injections of cocaine. These experiments indicate the feasibility and utility of second-order schedules in studying the neurobehavioural basis of cocaine-seeking behaviour. They suggest a dissociation in the neural mechanisims underlying cocaine-taking and cocaine seeking behaviour, and demonstrate the potential importance of the Basolateral Amygdala in the processes by which previously neutral stimuli gain control over drug-seeking behaviour.
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Differential effects of excitotoxic lesions of the Basolateral Amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of D-amphetamine
Behavioural brain research, 1993Co-Authors: Lindsay H. Burns, Trevor W. Robbins, Barry J EverittAbstract:Abstract The experiments reported here have investigated the impact on reward-related processes of lesioning the Basolateral Amygdala, ventral subiculum and prelimbic cortex which represent the major limbic sources of afferents to the ventral striatum. The results showed that, while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. However, there were important differences between the effects of Basolateral Amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completely abolished the locomotor response to intra-accumbens infusions of d -amphetamine, in addition to blocking the potentiative effect of the same treatment on responding with conditioned reinforcement. Lesions of the Basolateral Amygdala, by contrast, reduced the control over behaviour by a conditioned reinforcer, but not the potentiation of that control by intra-accumbens d -amphetamine except at the highest dose. Moreover, the locomotor response to d -amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected by Amygdala lesions over the dose range blocked by ventral subiculum lesions. The results suggest a rather selective effect of Amygdala-ventral striatal interactions on processes subserving conditioned reinforcement and a more fundamental influence of ventral subiculum-ventral striatal interactions in mediating the psychomotor stimulant effects of d -amphetamine.
Floris Klumpers - One of the best experts on this subject based on the ideXlab platform.
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the Basolateral Amygdala is essential for rapid escape a human and rodent study
Cell, 2018Co-Authors: David Terburg, Barak Morgan, Estrella R Montoya, Floris Klumpers, Diego Scheggia, Rodrigo Trianadel Rio, Alexandru Cristian Ciobanu, Peter A Bos, Gion GiobellinaAbstract:Rodent research delineates how the Basolateral Amygdala (BLA) and central Amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species, an essential role for the BLA in the selection of active escape over passive freezing during exposure to imminent yet escapable threat (Timm). In response to Timm, BLA-damaged humans showed increased startle potentiation and BLA-silenced rats demonstrated increased startle potentiation, freezing, and reduced escape behavior as compared to controls. Neuroimaging in humans suggested that the BLA reduces passive defensive responses by inhibiting the brainstem via the CeA. Indeed, Timm conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient Timm responses in BLA-silenced rats. Our data reveal how the BLA, via the CeA, adaptively regulates escape behavior from imminent threat and that this mechanism is evolutionary conserved across rodents and humans.
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impaired acquisition of classically conditioned fear potentiated startle reflexes in humans with focal bilateral Basolateral Amygdala damage
Social Cognitive and Affective Neuroscience, 2015Co-Authors: David Terburg, Barak Morgan, Dan J. Stein, J. Van Honk, Floris KlumpersAbstract:Based on studies in rodents, the Basolateral Amygdala (BLA) is considered a key site for experience-dependent neural plasticity underlying the acquisition of conditioned fear responses. In humans, very few studies exist of subjects with selective Amygdala lesions and those studies have only implicated the Amygdala more broadly leaving the role of Amygdala sub-regions underexplored. We tested a rare sample of subjects (N ¼ 4) with unprecedented focal bilateral BLA lesions due to a genetic condition called Urbach–Wiethe disease. In a classical delay fear conditioning experiment, these subjects showed impaired acquisition of conditioned fear relative to a group of matched control subjects (N ¼ 10) as measured by fear-potentiation of the defensive eye-blink startle reflex. After the experiment, the BLA-damaged cases showed normal declarative memory of the conditioned association. Our findings provide new evidence that the human BLA is essential to drive fast classically conditioned defensive reflexes.