2004 — 2006 |
Parsons, Ryan G |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Reconsolidation of Fear Memory @ University of Wisconsin Milwaukee
DESCRIPTION (provided by applicant): The long-term goal of this project is to understand how the brain stabilizes memories after they have been retrieved. Using rats, this project will focus on the contribution of transcriptional and translational processes during the periods following retrieval of stored memory. The contribution of these processes will be elucidated using two main approaches. The first approach is to use targeted infusion of drugs that prevent either protein (translation) or mRNA (transcription) synthesis into brain regions known to be involved in fear conditioning. The second approach is to use antisense oligodeoxynucleotides (ODNs) to examine the role that specific proteins play in stabilizing memory after retrieval. These goals will be achieved with a series of experiments. In these experiments rats will be trained to fear a neutral conditional stimulus (CS) paired with an unconditional stimulus (UCS). A day later, animals will be "reminded" of this association with short presentations of CS, and drug infusions will immediately follow. Memory will be assessed the final day by longer exposures to the CS. These experiments will answer questions about which brain areas and molecular processes contribute to the stabilization of fear memory after retrieval and, in general, should reveal the physiological underpinnings of how memory changes after retrieval.
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0.966 |
2010 — 2012 |
Parsons, Ryan |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
The Maintenance of Fear Memories in the Amygdala
DESCRIPTION (provided by applicant): Pavlovian fear conditioning has proved to be a useful model for the study of the cellular mechanisms of fear learning and memory. Considerable progress has been made in understanding the neural mechanisms that support this form of learning, but very little is known about how fear memories persist in the face of protein turnover. The amygdala is thought to be critical to the acquisition and storage of fear memory, but how this occurs at the cellular level has yet to have been fully answered. Recent studies suggest that protein kinase M zeta (PKM6) becomes persistently active following learning and may support synaptic activity underlying the maintenance of long-term memories. The work in this proposal is designed to explore several questions about how fear memories are maintained in the amygdala. We will test if the deficits in memory following PKM6 inhibition are permanent and if amygdala-dependent fear memories rely on PKM6 activity regardless of the age of the memory. We will also test the hypothesis that the maintenance of fear memory in the amygdala is supported by the trafficking of GluR2 containing 1-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors, which is thought to be controlled by PKM6. Finally, we will use lentiviral vectors to determine if neurons that are involved in the initial acquisition of fear memory are the same cells that use PKM6 to maintain the memory. The long-term goal of the work in this proposal is to reach a better understanding of the fundamental issue of how memories are stored in the brain. The work in this proposal is potentially very useful in coming to a full understanding of how various organic amnesias and psychopathologies develop and persist. PUBLIC HEALTH RELEVANCE: The long-term goal of the work in this proposal is to reach a better understanding of the fundamental issue of how memories are stored in the brain. The work in this proposal is potentially very useful in coming to a full understanding of how various organic amnesias and psychopathologies develop and persist.
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0.915 |
2011 |
Parsons, Ryan G |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Maintenance of Fear Memories in the Amygdala
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Recent studies suggest that protein kinase M zeta (PKM[unreadable]) becomes persistently active following learning and may support synaptic activity underlying the permanent storage of long-term memories. If this is the case, inhibiting PKM[unreadable] in the amygdala should permanently erase fearful long-term memories. The work over the last year tested whether PKM[unreadable] inhibition in the amygdala permanently disrupts fear memory by assessing memory at various intervals after PKM[unreadable] blockade. Although the expression of fear memory was disrupted when the inhibitor was applied shortly before testing, it had no effect when rats were tested with longer retention intervals. These results suggest that PKM[unreadable] inhibition does not erase memory, but temporarily disrupts expression of memory. The long-term goal of the work in this proposal is to reach a better understanding of the fundamental issue of how memories are stored in the brain. The work in this project is potentially very useful in coming to a full understanding of how various organic amnesias and psychopathologies develop and persist.
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1 |
2020 |
Parsons, Ryan G |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Ion Channel Plasticity and Aversive Memory Priming @ State University New York Stony Brook
Project Summary The acquisition and persistence of an aversive memory is a central component of fear-based disorders such as post-traumatic stress disorder. Pavlovian fear conditioning uses neutral cues that predict the occurrence of an aversive event, typically a mild electric shock. After pairings of the cue with shock, organisms will exhibit behaviors that are consistent with the expression of fear, and which we measure to infer that learning has taken place. This form of learning is widely used as a model system for studying how fear-based memories are formed, and the study of fear conditioning has yielded detailed knowledge regarding the cellular and molecular mechanisms necessary for fear memory formation. Much of this work has used training procedures in which memories were acquired in isolation from other controlled experiences. However, memories are not normally acquired in isolation from other experiences, and in fact can be influenced by prior experiences. As an example, our previous studies have showed that prior fear conditioning can facilitate the acquisition of new fears when another cue is presented and paired with shock hours or days later. Given the profound influence of prior experience, identifying the mechanisms by which past experience impacts later learning is essential to our understanding of learning and memory. Our long-term goal is to understand the neurobiological mechanisms that allow prior fear conditioning to alter subsequent fear learning. The objective in this proposal is to determine whether or not changes in the expression of specific ion channel proteins are required for the ability of the initial experience to prime subsequent learning, memory formation for an initial experience, or both processes. Our hypothesis is that changes in expression of sodium channels containing the 1-beta subunit, and Kv4.2 potassium channels, play a specific role in the priming of future learning, but are not required for memory formation or the expression of fear behavior. To achieve this objective, we will combine behavioral studies, with protein and RNA expression analysis, and site-specific RNA interference. In specific Aim 1, we will test if the ability of an initial fear conditioning trial to prime later learning depends on altered expression of sodium channels containing the 1-beta subunit in the basolateral amygdala. In specific Aim 2, we will test the involvement of the Kv4.2 potassium channel. This project is focused on describing the neural mechanisms that allow prior experience prime future memory formation. The basic information gained here has implications for the etiology of fear-based disorders and ultimately may open up new avenues for their treatment.
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1 |