2005 — 2007 |
Pfeiffer, Brad E |
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.). |
Role of Fmrp in Synaptic Function and Plasticity @ University of Texas SW Med Ctr/Dallas
[unreadable] DESCRIPTION (provided by applicant): Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of function of the Fragile X Mental Retardation Protein (FMRP). Studies of FXS patients and mouse models of FXS suggest that FMRP is critical for proper synaptic function and plasticity. I propose to investigate the role of FMRP in synaptic function through three major aims: 1) Electrophysiological measurements of synaptic function following transient alteration of FMRP expression levels in organotypic hippocampal slice cultures (OHSCs) and through the use of FMRP mutants; 2) Electrophysiological analysis of synaptic plasticity in FMRP-overexpressing mice and in OHSCs following transient overexpression of FMRP and FMRP mutants; and 3) Biochemical analysis of glutamate receptor expression and trafficking in FMRP-overexpressing and FMRP-knockout mice and in OHSCs following transient alterations in FMRP expression. This research should give substantial insight into the role of FMRP at the synapse and may provide impetus for the generation of a treatment for FXS. [unreadable] [unreadable]
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0.918 |
2018 — 2021 |
Pfeiffer, Brad E |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mechanisms of Expression and Relationship Between Two Distinct Types of Internally Generated Hippocampal Sequences @ Ut Southwestern Medical Center
PROJECT SUMMARY/ABSTRACT The brain expresses several distinct types of internally generated sequences of neuronal activity independent of external sensory stimuli, and such temporally precise, self-organized sequences play a crucial role in information processing and memory formation/retrieval. In particular, the hippocampus generates two separate, well-defined forms of neuronal sequences: sharp-wave/ripple (SWR)-associated sequences which are observed during ?off-line? states such as rest or sleep, and theta-associated sequences which occur during ?on-line? states such as active exploration. Prior work has demonstrated a link between SWR sequences and working memory, long-term memory, and future planning, while theta sequences have been associated with decision-making and immediate future behaviors. However, little is known regarding how these two sequence types interact with experience or each other to facilitate mnemonic processes. Further, the circuit mechanisms which allow specific neuronal activity patterns to be expressed within internally generated sequences are largely unknown. The central objective of this study is to utilize ultra-high density, large-scale in vivo electrophysiology coupled with complex spatial navigational tasks to examine in depth these two forms of sequential activity to identify fundamental principles which underlie their generation, function, and relationship to each other. Supported by considerable preliminary data, we propose to pursue this objective through three specific aims: (1) To define the relationship between internally generated sequences and ongoing behavior during periods of memory formation vs. memory retrieval/use; (2) To determine the mechanisms underlying development, persistence, and function of internally generated sequences in sleep; (3) To identify how the patterns and weights of connectivity within the hippocampus contribute to the expression and propagation of internally generated sequences. Together, this study is expected to meaningfully advance our understanding of circuit-level brain function by revealing the fundamental principles which allow precise patterns of activity to be dynamically generated and propagated throughout the hippocampal network in support of learning.
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0.993 |