Browsing by Subject "hippocampus"
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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 Regular treadmill exercise prevents sleep deprivation-induced impairment of hippocampal-dependent memory and synaptic plasticity(2012-04-19) Zagaar, Munder; Alkadhi, Karim; Eriksen, Jason; Salim, Samina; Grill, Raymond; Alcantara, AdrianaABSTRACT Study Objectives: Evidence suggests that regular exercise can protect against learning and memory impairment in the presence of insults such as stroke and neurodegeneration. The purpose of this study was to determine the effect of regular exercise on hippocampus-dependent learning and memory impairment associated with sleep deprivation. Experimental Design: We investigated the effects of 4 weeks of regular treadmill exercise on learning and memory impairment in 24 hour sleep-deprived rats. Sleep deprivation was accomplished using the columns-in-water model. We tested the effects of exercise and/or sleep deprivation using three approaches: the radial arm water maze (RAWM) task to test spatial learning and memory performance; electrophysiological recording in the Cornu Ammonis (CA1) and dentate gyrus (DG) areas of the hippocampus to measure synaptic plasticity; and western blot analysis to quantify the levels of key signaling molecules that are related to memory and synaptic plasticity. Results: In the RAWM, regular exercise prevented the sleep deprivation-induced impairment of spatial learning, short-term memory, and early-phase long-term potentiation (E-LTP) in both CA1 and DG areas. In correlation, exercise prevented the sleep deprivation-associated decrease in basal levels of phosphorylated and total calcium/calmodulin-dependent protein kinase II (P/total-CaMKII) and brain-derived neurotrophic factor (BDNF). High frequency stimulation (HFS), which increased the P-CaMKII and BDNF levels in normal animals, did not change these levels in sleep-deprived rats but did increase levels of the phosphatase calcineurin. In contrast, exercise increased BDNF and P-CaMKII levels in exercised/sleep-deprived rats, probably by preventing increases in calcineurin levels, thus maintaining appropriate P-CaMKII levels. Regular exercise also prevented the sleep deprivation-induced impairment of long-term memory and late-phase LTP. In correlation, exercise increased the basal levels of phosphorylated cAMP response element binding protein (P-CREB) and total-CREB as well as P/total- mitogen activated protein kinase (MAPK/ERK) in CA1 and DG areas of sleep-deprived rats. Also, exercise allowed multiple HFS to increase the levels of BDNF and P/total-CREB during L-LTP expression in sleep-deprived rats. Conclusions: These findings suggest that sleep deprivation impairs both the CA1 and DG areas whereas exercise prevents this impairment. Regular exercise exerts a protective effect against sleep deprivation-induced impairment probably by inducing BDNF expression, which can positively modulate basal and/or stimulated levels of P-CaMKII, P-CREB, P-MAPK/ERK and calcineurin. As a result, exercise-induced BDNF could contribute to the restoration of hippocampus-dependent learning and memory as well as LTP in both CA1 and DG areas.