1,721,022 research outputs found
Basolateral amygdala circuits in detailed associative reward memory
Get PDFTo make good decisions we often rely on detailed associative memories to infer the availability of prospective rewards from predictive cues within the environment. These stimulus-outcome relationships are essential elements of our cognitive map that links specific outcomes to antecedent cues and the specific actions needed to obtain them. This internal model enables us to project into the future, anticipate the consequences of our actions and adapt our behaviors accordingly (i.e., model-based decision making). The research presented here investigated neural circuitry mediating the encoding and subsequent retrieval of outcome-specific reward memories. Targeted optical manipulation and recording methods revealed the basolateral amygdala (BLA) as a central hub for detailed stimulus-outcome associations. The BLA was robustly activated by the delivery of distinct food outcomes preceded by auditory stimuli and this activity was necessary for encoding sensory-specific cue-reward memories. This function was supported by modulatory inputs from ventral tegmental dopamine neurons (VTADA). Optically manipulating VTADABLA axonal terminals during Pavlovian conditioning and in a novel Pavlovian blocking paradigm revealed these inputs are both necessary and sufficient to drive outcome-specific learning. Excitatory projections from the lateral orbitofrontal cortex (lOFC) were also essential for facilitating the BLA in encoding these associations. Moreover, reciprocal lOFCBLAlOFC connections formed an encoding and retrieval circuit. Associative memories are complex, containing information about stimuli, motivational state, outcome identity, value, etc. A pathway-specific serial disconnection revealed that the component of the associative memory that was encoded through activation of lOFCBLA projections was the same as that which was later accessed through BLAlOFC projections to enable cue motivated adaptive reward seeking. Collectively, these data uncover neural substrates for detailed associative reward memories that enable model-based decision making.
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The Interaction of Nucleus Accumbens Core Acetylcholine and Dopamine in Motivated Reward Seeking
Get PDFReward-seeking behaviors can be guided by both internal and external factors. Dopaminergic signaling within the nucleus accumbens core (NAc) has been heavily implicated in reward-related learning and motivation. However, it was unclear what dopaminergic release profile occurs with learning a sequence of actions in which sustained motivation is required to complete the task and procure a reward. Investigation revealed a ramp-like profile that corresponded with learning and motivational aspects of the task. In addition to self-guided reward seeking, external cues that predict reward are also capable of motivating reward seeking. NAc dopamine signaling has been highly implicated in this as well, but additional modulators within the NAc, such as acetylcholine, are poorly understood. Therefore, I investigated the role of the NAc cholinergic system in regulating cue-motived reward seeking. Results suggest that the cholinergic system acts as a regulatory gate over cue-motivated reward seeking, with increases in activity suppressing, and decreases augmenting, this behavior. Additionally, evidence indicates that the NAc cholinergic system provides this suppressatory gate on cue-motivated behavior, at least in part, via terminal modulation of dopamine release
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Neural and Behavioral Correlates of Adaptive and Maladaptive Behavior
Get PDFFor many years, researchers have worked to understand the nuances of behavior, from understanding how the brain fundamentally makes decisions to meet our needs, to how our behavior can become maladaptive, leading us to forgo our basic needs and develop dependence on drugs. Understanding the basic neural systems that underlie reward-related decision making, including how reward-paired stimuli inform reward pursuit decisions, can help clarify what changes occur in the brain following opioid exposure, and how those changes drive drug pursuit and decision making biased towards drugs and away from adaptive rewards. The research presented here discusses potential pathways involved in reward valuation and decision making, and a behavioral model to study decision making between natural and drug rewards. Using pathway-specific chemogenetic inactivation during a memory retrieval task, I have shown that projections between the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) may be critical for using environmental stimuli to make reward value predictions to guide reward behavior. Rats with inactivation of BLA axon terminals in the ACC, and ACC terminals in the BLA, showed deficits in using the recently updated value of one of two food rewards to guide their behavior during an extinction probe test. Further investigation of these pathways using alternative methods, including optogenetic and/or dual viral intersectional chemogenetic approaches, will clarify the roles of these pathways.
Pathways involved in reward valuation for adaptive rewards (e.g. food) likely contribute to drug reward valuations and, in turn, contribute to decision making processes that may drive the development of substance dependence. Further, stress and trauma are also known to contribute to substance use disorders. To study how trauma may influence drug-related behavior, I developed a novel food vs. opioid (fentanyl) decision making task to overcome several limitations of canonical drug self-administration studies, combined with stress-enhanced fear learning (SEFL), a well-established rodent model of posttraumatic stress disorder (PTSD). While I did not detect effects of SEFL on opioid behavior, the results suggest several future directions to address the known human PTSD-opioid use disorder comorbidity in preclinical models that can then inform development of behavioral interventions and pharmacotherapies
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How Diet Can Alter Reward-Seeking Behavior
Get PDFThe epidemic of chronic, preventable diseases such as obesity and diabetes remain a serious health concern, driven largely by 1) changes in the global food supply as the consumption of nutritive foods decreases and that of highly refined and processed foods increases, and 2) a subsequent inability to limit food consumption appropriately. While obesity remains at the forefront of preventable diseases, recent evidence suggests that it is strongly associated with insulin resistance and type 2 diabetes, so much so that the phrase “diabesity” has been coined to emphasize their comorbidity. Growing evidence suggests that the foods we eat can have serious consequences not just in the periphery (e.g., weight gain), but can alter our neurochemistry and behavior as well. The experiments presented here probe this issue in two parts. First, we examine whether a junk food diet can alter the use of external and internal cues to guide reward seeking behavior. To this end, we used general and outcome-specific Pavlovian-to-instrumental transfer (PIT) tests to probe incentive motivation and decision making, respectively, and a test of outcome devaluation to examine the sensitivity of reward seeking to a decrease in outcome value, after either intermittent or ad libitum junk food exposure. We found that intermittent junk food exposure disrupts general and outcome-specific PIT, promoting reward seeking in response to cues only loosely paired with reward and inconsistent with outcomes predicted by the cue. Ad libitum junk food exposure suppresses reward seeking during a general PIT test, and disrupts outcome-specific PIT similarly to intermittent junk food exposure. Junk food exposure also disrupts the ability of internal, interoceptive cues about satiety state to adjust reward seeking in a test of outcome devaluation, irrespective of the pattern of junk food exposure.We also examined whether an insulin-disrupting high fructose diet would alter incentive motivation in a general PIT test. We used fast-scan cyclic voltammetry to examine dopamine signaling during the PIT test, and in anesthetized animals to further assess dopamine reuptake kinetics. We found that insulin resistant rats were behaviorally and neurochemically sensitive to both reward-paired and “neutral” cues, demonstrating increased reward seeking and phasic dopamine release in response to both types of cues. We also found that dopamine reuptake was prolonged in insulin resistant rats, and that treatment with the insulin receptor sensitizing drug pioglitazone normalized reuptake and incentive motivation
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Amygdala-cortical circuits in associative reward memory retrieval
Get PDFAdaptive decision making requires the accurate anticipation or expectation of rewarding events. To survive in our environment, we must retrieve and use detailed associative memories of reward-predictive cues and actions taken to reach a goal to inform and guide our decisions. Often times, this cognitive process and underlying neural mechanisms can go awry, leading to maladaptive reward representation and improper choice behavior. Here, we elucidate the basic brain mechanisms of reward-expectation guided behaviors by employing neuroanatomical tracing alongside targeted pharmacological and chemogenetic manipulations of neural circuitry. The data presented here reveal novel contributions of a basolateral amygdala (BLA) opioid receptor system and of specific amygdala-cortical projection pathways to cue-guided behavior.First, we reveal that the endogenous activation of mu-, but not delta-opioid receptors in the BLA are needed for a reward-predictive cue to guide action selection. BLA mu-opioid receptor antagonism did not disrupt the ability of a reward itself to influence actions, suggesting a selective role for this receptor in mediating cue-outcome memory retrieval. Next, we sought to understand the role of the BLA within a larger neural network, so we first used anterograde and retrograde tract tracers to anatomically map populations of BLA projection neurons to the medial (mOFC) and lateral (lOFC) orbitofrontal cortices, and also identified reciprocal overlap in BLA-OFC (orbitofrontal) circuitry within the frontal cortex. We found spatially distinct populations of BLA→mOFC and BLA→lOFC neurons and dense overlap between OFC cell bodies and BLA terminals in the mOFC and lOFC. Thereafter, we causally manipulated pathways within the BLA-OFC network using a novel projection-specific chemogenetic approach during a series of behavioral tasks designed to assess the retrieval and use of cue- and action-outcome memories. BLA→lOFC projections were required for cue-guided action selection and responding according to a reward’s current value, while BLA→mOFC projections were only required for the latter. Much like the BLA→lOFC pathway, mOFC→BLA projections were needed for reward-predictive cues to guide action selection, and for such cues to influence responding according to a reward’s current value. lOFC inputs to the BLA were not needed for cue-guided action selection, and no projection was found to be necessary for action selection based on a reward’s current value. Taken together, these data provide evidence that distinct projection pathways in the BLA-OFC network coordinate unique and overlapping aspects of reward expectation-guided behaviors, particularly when these behaviors are informed by reward-predictive environmental cues. Often times, mental illness is characterized by improper reward expectation or foresight because patients are deficient in mentally representing anticipated rewards and in reward valuation. Therefore, the findings presented in this work may contribute to our understanding and treatment of psychiatric disease, such as addiction, and suggest that they may arise due to dysfunctional amygdala-OFC circuits
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The basolateral amygdala in reward learning and addiction.
Get PDFSophisticated behavioral paradigms partnered with the emergence of increasingly selective techniques to target the basolateral amygdala (BLA) have resulted in an enhanced understanding of the role of this nucleus in learning and using reward information. Due to the wide variety of behavioral approaches many questions remain on the circumscribed role of BLA in appetitive behavior. In this review, we integrate conclusions of BLA function in reward-related behavior using traditional interference techniques (lesion, pharmacological inactivation) with those using newer methodological approaches in experimental animals that allow in vivo manipulation of cell type-specific populations and neural recordings. Secondly, from a review of appetitive behavioral tasks in rodents and monkeys and recent computational models of reward procurement, we derive evidence for BLA as a neural integrator of reward value, history, and cost parameters. Taken together, BLA codes specific and temporally dynamic outcome representations in a distributed network to orchestrate adaptive responses. We provide evidence that experiences with opiates and psychostimulants alter these outcome representations in BLA, resulting in long-term modified action
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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