Date of Award
Spring 5-1-2022
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biology
First Advisor
Dr. Ashok Hegde
Second Advisor
Dr. Ellen France
Third Advisor
Dr. Matthew Milnes
Abstract
The hippocampus is the region of the brain responsible for the formation and storage of memory for places, events, and things. In order for memories to be stored for long periods of time, the connections between nerve cells called synapses must get stronger. The ability of the synapses to change in strength is termed synaptic plasticity which can last a few minutes (short-term) or for days and years or even a lifetime (long-term). Previous research pointed to the requirement of new gene transcription and protein synthesis for long-term synaptic plasticity. Research over the past several years indicates that protein degradation by the ubiquitin-proteasome pathway (UPP) is a key player in inducing long-term synaptic plasticity. In addition, new research suggests that apart from functioning in protein degradation, the proteasome may have a non-proteolytic role in assisting transcription. We hypothesize that the proteasome, made up of a 20S core and two 19S regulatory caps attached to each end of the core, plays a vital role in transcription that is necessary for maintenance of long-term synaptic plasticity. An experimental paradigm used to study long-term synaptic plasticity is called late phase long-term potentiation (L-LTP). Preliminary data show that the role of the proteasome in transcription may be essential for L-LTP. To understand the role of the proteasome in transcription, it would be necessary to identify the genes whose transcription is regulated by the proteasome during development of L-LTP. The research focused on a specific 19S subunit called Rpt1 and its nuclear translocation with a view to elucidate its transcriptional role. The experiments identified amino acid sequence elements critical for nuclear translocation of Rpt1 and revealed details of gene transcription possibly modulated by Rpt1.In combination with other ongoing projects and related research, our work is contributing to a mechanistic understanding of molecules critical for long-term synaptic plasticity that underlies long-term memory. This may assist in identifying novel therapeutic targets for memory loss that occurs in various neurodegenerative diseases.
Recommended Citation
Duke, Lindsey, "The Nuclear Role of Rpt1 in Long-Term Synaptic Plasticity" (2022). Biology Theses. 23.
https://kb.gcsu.edu/biology/23