Browsing by Subject "Extinction"
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Item Affective responses in cocaine-experienced rats reveal cue-induced drug craving and cocaine reward magnitude(2011-08) Maier, Esther Yvonne; Duvauchelle, Christine L.; Schallert, Timothy; Gonzales, Rueben A.; Gore, Andrea C.; Monfils, Marie H.The development and persistence of cocaine dependence are greatly influenced by emotional affect and cocaine associative learning. Cocaine is known to enhance nucleus accumbens (NAcc) dopamine, serve as a positive reinforcer and produce negative effects, such as anxiety that may influence cocaine intake behavior. In the first study, I investigated the effects of the anxiolytic, diazepam on NAcc dopamine levels and cocaine self-administration behavior. These are two factors associated with cocaine rewarding effects. Diazepam has no effect on NAcc dopamine, but affects cocaine self-administration. This supports the notion that decreasing the anxiogenic effects of cocaine increases the rewarding value in a dopamine independent manner. Therefore, increasing the aversive effects of cocaine might be a novel approach to fight cocaine dependence. In the second study, I studied cocaine-induced associative learning and changes in affect during cocaine conditioning and extinction. 50-kHz ultrasonic vocalizations (USVs) in rats are thought to reflect positive affect and occur upon appetitive stimuli and with cocaine delivery. First, I explored whether USVs might be elicited in anticipation of impending drug delivery. Shortly into conditioning, rats elicited USVs when placed in the cocaine-associated environment. USVs progressively increased, indicating a growing learned association between cocaine intake and cocaine-associated cues. This suggests that USVs may be a useful model for investigating cocaine craving and serve as a pharmacological target for interventions aimed to reduce cocaine craving and relapse. I then examined the effects of short-term deprivation of cocaine and cocaine cues on cocaine-conditioned USVs, which were both exaggerated after abstinence. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and increase the probability of relapse. Motivational aspects of cocaine were assessed comparing commonly measured lever response rate and locomotion with cocaine-induced USVs during cocaine administration and extinction. In agreement with prevailing findings, lever responding for cocaine and cocaine-induced locomotor activity increased across conditioning sessions. However, the number of USVs evoked in response to cocaine infusion decreased with cocaine experience. These findings suggest growing tolerance to the rewarding properties of cocaine. These studies underscore the value of USV assessment during drug dependence studies.Item An evaluation of resurgence of appropriate communicative responses in children with developmental disabilities(2011-08) Hoffman, Katherine J.; Falcomata, Terry S.; Ringdahl, JoelThe purpose of the current study was to evaluate the conditions under which resurgence of appropriate communicative responses (mands) would occur with children with developmental disabilities. The experimental preparation consisted of a sequence of conditions that included (a) the reinforcement of one mand (i.e., microswitch activation or card exchange) on a FR 1 schedule, (b) an extinction condition in which the mand was no longer reinforced, (c) the reinforcement of a second mand (i.e., microswitch activation or card exchange) on a FR 1 schedule, and (d) a test for resurgence of the first mand which consisted of placing the second mand on extinction. The results demonstrated resurgence of mands during 2 out of 3 tests for resurgence for one participant. Resurgence of mands was demonstrated during all three tests for resurgence with the second participant.Item How to achieve Extinction without killing yourself : the process of writing a screenplay(2010-08) Zisman, Noah Ira; Kelban, Stuart; Garrison, Andrew“How to Achieve Extinction Without Killing Yourself: The Process of Writing a Screenplay” examines the creative procedure of writing the sci-fi feature Extinction. It explores the step-by-step process of idea genesis through to the third draft.Item Nocturnal giants and brainy birds : ecological evolution across early avian divergences(2020-12-11) Torres, Christopher Robert; Clarke, Julia A.; Cannatella, David C.; Edwards, Scott; Hillis, David; Zakon, HaroldThe identification of fossilizable correlates to ecology is essential for estimating the biology of extinct organisms. Among birds, reconstructions of brain shape and wing shape can elucidate macroevolutionary patterns in sensory and locomotory ecology. Here, I use these data to estimate traits ancestral to the crown avian divergence that may have contributed to their exceptional survival of the end-Cretaceous extinction event, as well as to the basal divergences within Palaeognathae, a clade marked by repeated losses of flight and gigantism. First, I use digital brain reconstructions to investigate the evolution of palaeognath sensory ecology. I find relatively large olfactory bulbs in taxa occupying forested environments where visual cues used in foraging are likely to be limited. Elephant birds exhibited extremely reduced or obsolete optic lobes, a condition only observed among extant birds in nocturnal taxa. I interpret these results as evidence for nocturnality among elephant birds. Next, I reconstruct the wing of an exceptionally preserved specimen of the Early Eocene lithornithid Calciavis grandei. Lithornithids are stem flying palaeognaths, and investigations of properties of their wings informs estimation of ancestral traits in Palaeognathae. My comparison of flight parameters estimated for Calciavis with representatives from across Aves show that it was likely capable of sustained flight and migratory behavior, consistent with previous hypotheses the ancestors of extant palaeognath lineages may also have been capable of sustained flight. Finally, I use data from a new, nearly complete skull of Late Cretaceous (~70 Ma) near-crown bird Ichthyornis to interrogate hypotheses proposed to explain patterns of dinosaur survivorship of the end-Cretaceous mass extinction and reassess bird body size evolution. These hypotheses demand identification of traits unique to survivors in Aves. However, identification of such traits is complicated by data available from stem birds. Ichthyornis exhibited a wulst and segmented palate, features with controversial evolutionary timing. The origin of Aves is marked by larger, highly flexed brains indicating selection for relatively large telencephela and eyes but were not uniquely small bodied. Sensory system differences, potentially linked to these shifts, may help explain avian survivorship relative to other dinosaurs.Item Presentation: The Rock that Changed the World(Environmental Science Institute, 2008-03-02) Environmental Science Institute; Gulick, SeanItem Temporal factors and ensemble coding of contextual fear and extinction memories in the hippocampus(2018-10-10) Lacagnina, Anthony Frank; Drew, Michael R., Ph. D.; Mauk, Michael D; Monfils, Marie H; Zemelman, Boris V; Maren, StephenFearful experiences create long-term memories that involve acquiring a negative association to the surrounding context. Exposure to the same context at a later time elicits a fearful response, but this learned behavior will diminish in the absence of threat, a process known as extinction. Extinguished fear often relapses; thus, a better understanding of the behavioral and neural mechanisms that influence how fear and extinction memories are acquired and expressed is crucial to develop better therapies. The goals of the experiments in this dissertation were to understand the temporal factors and ensemble coding mechanisms that govern the enhancement or suppression of contextual fear learning. First, we investigated the influence of postshock context exposure in contextual fear conditioning (CFC). We found that prolonging the amount of postshock context exposure reduced conditioned fear. The reduction was more effective than an equivalent amount of context exposure the following day, but required low levels of freezing during the postshock period. Thus, unique mechanisms may play a role in attenuating context fear depending on the timing of the exposure and the emotional state of the animal. Next, we determined if the interval between context pre-exposure and conditioning affected one-trial CFC. Increasing the time between pre-exposure and conditioning by at least 1 h led to enhanced conditioned fear, indicative of a trial spacing effect. Spacing the sessions increased reactivation of CA3 ensembles associated with fear acquisition, suggesting this may be a potential neural correlate of the spacing effect. Finally, we investigated the neural mechanisms governing expression of competitive fear and extinction memories in the dentate gyrus (DG), a region known to play an important role in acquiring both fear and extinction memories. Using an activity-dependent neural tagging system, we demonstrate that extinction training suppresses reactivation of fear-associated DG neurons, while activating a unique population of extinction-associated DG neurons. Optogenetically silencing extinction-associated neurons impairs extinction memory retrieval, while silencing fear-associated neurons prevents spontaneous recovery of fear. Our results suggest that extinction training creates a unique DG extinction engram whose activity is necessary for extinction expression. We hypothesize that interactions between the fear and extinction engrams in the DG govern the expression of fear and extinction memoriesItem The influence of exercise on persistence of fear(2017-07-24) Roquet, Rheall Florene; Monfils, Marie-H.; Lee, Hongjoo J; Jones, Theresa A; Powers, Mark BPavlovian fear conditioning has been used for almost a century to better understand how fear is acquired and remembered, as well as to find ways to augment the learning and memory process to change memories and create new competitive memories, in an investigation to reduce the persistence of fear. The current work set out to determine if acute and/or chronic exercise could reduce persistence of fear. First, after early life fear exposure (at post-natal day 17 [P17] or 25 [P25]) rats were given a chronic regimen of exercise during late adolescence to determine if exercise could influence memory recall or fear learning (or re-learning) in adulthood. Results indicate a difference in memory based on age of fear exposure, such that rats conditioned at P25 but not P17 show increased levels of freezing when tested in adulthood. While P17 conditioned rats, do not show a fear memory, increases in the average distance run did predict less freezing during the retention test, suggesting an influence on generalized anxiety rather than fear memory directly. Conversely, irrespective of early P25 condition, exercise produced a similar negative correlation on the fear response after adult fear learning; such that increased distances run predicted lower levels of freezing. Following these tests of chronic exercise, acute 30-minutes and 3-hours of exercise prior to extinction/exposure were shown not to enhance reductions in fear on either long-term memory or fear relapse tests, for neither cued nor contextual fear paradigms. Finally, a meta-analytical approach was employed to disentangle when and under what conditions exercise could enhance fear extinction, but also its influence on other Pavlovian and operant extinction models within the literature. Results indicate that exercise significantly enhanced reductions in responding for operant but not Pavlovian models, with different moderators under both models. Interestingly, it was found that exercising after Pavlovian extinction was critical to larger reductions in responding over extinction alone, which may account for the lack of enhancement seen in my previous findings. Taken together the potential for exercise to reduce the persistence of fear may depend on the timing of application and whether you’re targeting learning or memory.Item Ventral hippocampal regulation of contextual fear and extinction memory(2023-12) Brockway, Emma Taylor; Drew, Michael R.; Colgin, Laura L; Dunsmoor, Joseph E; Zemelman, Boris V; Maren, StephenFear learning creates long-term memories through which predictive cues or the context surrounding the fearful event acquire negative associations. Later exposure to these stimuli elicits a fearful response, but this learned response will diminish in the absence of threat, a process known as extinction. Extinction does not abolish fear memory, but instead creates a separate memory of safety. The hippocampus is thought to be a hub for competition of the expression of these two opposing memories. Neural ensemble representations of contextual fear and extinction memories are distinct in the hippocampus, but how these memories are processed to influence recall and behavior is not known. These experiments sought to investigate activity in the ventral CA1 and subiculum (vHP), where projections to other fear and extinction related structures are located, to better understand how the hippocampus influences the expression and suppression of fear behavior. First, we investigated whether activity among vHP projections to the BLA and IL differed during context fear and extinction recall. We found that fear recall causes more activation of projections to BLA compared to IL, while extinction recall results in the opposite pattern of more activation of projections to IL than BLA. This shows that the ventral hippocampus is sensitive to the valence of contextual memory, and signals to relevant brain regions based on that valence. Next, we sought to selectively inhibit the projections from vHP to BLA and IL to test if these projections are indeed necessary for further recall of these memories. These manipulations were unsuccessful in impairing recall. Finally, we stimulated SST interneurons in vHP or IL to induce feed-forward inhibition. We found that stimulating vHP SST interneurons impaired fear recall, reducing fear behavior, and impaired extinction learning, resulting in higher fear behavior in a later test. This result demonstrates the vHP’s role in both context fear expression and suppression. Increasing inhibition in the IL did not affect context fear or extinction recall but did impair auditory cue extinction. Overall, these results provide evidence that vHP activity modulates context memory in a valence dependent way through connections to other fear related regions.