Browsing by Subject "extinction"
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Item Multiple memory systems and extinction: the neurobiological basis of latent extinction(2009-05-15) Gabriele, AmandaUnderstanding the neural mechanisms underlying the extinction of maladaptive behaviors has become increasingly relevant. Extinction, or the reduction of a response due to lack of reinforcement, is believed to be ?new learning.? Most extinction paradigms involve the performance of the previously reinforced response in the absence of reinforcement in order for extinction to occur. Conversely, latent extinction is a cognitive form of learning in which the previously rewarded response is not made during extinction training. However, until now the neurobiological basis of latent extinction has remained unknown. This dissertation has three aims to examine the neurobiological basis of latent extinction. Previous research has shown latent extinction to be impaired following hippocampal inactivation and the goal of Aim 1 was to examine other neural systems potentially involved in latent extinction through examination of brain structures such as the dorsal striatum, medial prefrontal cortex, and basolateral amygdala. Additionally, the neurochemical basis of latent extinction is unidentified; therefore Aim 2 addressed this question, specifically investigating the glutamatergic system through both NMDA receptor agonism and antagonism. Finally, understanding latent extinction may be useful for the extinction of drug addiction. Aim 3 was to examine some clinical implications for the extinction of drug addiction utilizing latent extinction following maze running for an oral cocaine reward. Reversible neural inactivation studies using the sodium channel blocker bupivacaine demonstrated a selective impairment of response extinction following dorsal striatum inactivation, but no effect on either latent or response extinction following medial prefrontal cortex or basolateral amygdala inactivation. These results, coupled with previous data from our lab demonstrate a double dissociation for extinction behavior. Further, peripheral NMDA receptor agonism with D-cyloserine enhances latent extinction and intra-hippocampal NMDA receptor antagonism with AP5 impairs latent extinction, identifying a role for the glutamatergic system in latent extinction. Finally, oral cocaine administration during acquisition selectively impairs latent extinction indicating that drug use affects the relive use of multiple memory systems during extinction. Overall, the multiple memory systems theory and latent extinction provide a framework with which to further understand the neural mechanisms of extinction behavior.Item Reversible Inactivation of the Bed Nucleus of the Stria Terminalis Blocks Reinstatement But Not Renewal of Extinguished Fear(2014-12-08) Kim, Janice JThe bed nucleus of the stria terminalis (BNST) is thought to be involved in the expression of fear to shock-associated contexts, but not to discrete conditional stimuli (CSs) paired with shock. Because context plays an important role in the extinction and relapse of fear, we sought to examine the contribution of the BNST to two different relapse phenomena: renewal and reinstatement. In the renewal experiment, male Long-Evans rats received 5 tone-shock trials for conditioning in ?context A?; 24 hours later they received 45 tone?alone (extinction) trials in either ?context B? or ?context C?. Ten minutes prior to a retrieval test (5 tone-alone trials), rats were infused with either selective agonist for GABAA receptors, muscimol or vehicle in the BNST. In the reinstatement experiment, rats underwent a similar procedure, but were presented with an unsignaled ?reminder? shock in the extinction context to reinstate fear. As before, we examined the influence of muscimol inactivation of the BNST during a retrieval testing 24-hours after the reinstatement shock. In the reinstatement test, rats with muscimol infusion showed significantly less freezing than did rats with vehicle infusion. In contrast, BNST inactivation did not attenuate the renewal of fear to an extinguished CS outside the extinction context. These data indicate that the BNST is involved in forms of fear relapse that depend on direct associations of the test context with an aversive US.