University of Illinois Urbana-Champaign

Modulation of hippocampal synaptic transmission by the peptide diazepam binding inhibitor and optogenetic manipulation of astrocytes

Courtney, Connor Duke

Content Files
COURTNEY-DISSERTATION-2021.pdf

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https://hdl.handle.net/2142/110530

Description

Title
Modulation of hippocampal synaptic transmission by the peptide diazepam binding inhibitor and optogenetic manipulation of astrocytes
Author(s)
Courtney, Connor Duke
Issue Date
2021-04-21
Director of Research (if dissertation) or Advisor (if thesis)
Christian-Hinman, Catherine A
Doctoral Committee Chair(s)
Christian-Hinman, Catherine A
Committee Member(s)
  • Rhodes, Justin S
  • Sweedler, Jonathan V
  • Tsai, Nien-Pei
Department of Study
Neuroscience Program
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2021-09-17T01:11:09Z
Keyword(s)
  • diazepam binding inhibitor
  • astrocyte
  • synaptic transmission
  • hippocampus
Abstract
Hippocampal synaptic transmission is an intricate and flexible entity that can be modulated, both directly and indirectly, by a variety of different signaling molecules and cell types. The peptide diazepam binding inhibitor (DBI) has complex physiological functions and is capable of both enhancing and attenuating inhibitory synaptic transmission in different brain regions. However, whether DBI modulates hippocampal synaptic transmission or hippocampal-dependent behaviors has not previously been studied. In addition, astrocytes are increasingly recognized as dynamic regulators of excitatory synaptic transmission. However, the extent to which astrocytes modulate inhibitory transmission remains unknown. The overall goal of this dissertation is to investigate the degree to which hippocampal synaptic transmission is modulated by both DBI and by optogenetic stimulation of local astrocytes. Chapter 2 investigates the role of DBI in modulating hippocampal synaptic inhibition using a constitutive DBI knockout animal. Chapter 3 continues to use the DBI knockout animals to examine the role of DBI in regulating both hippocampal-dependent and hippocampal-independent behavior. Chapter 4 utilizes a novel astrocyte-specific Gq-coupled optogenetic construct (Optoα1AR) to probe astrocytic modulation of hippocampal synaptic excitation and inhibition. The results here indicate that DBI differentially modulates hippocampal synaptic transmission in CA1 versus dentate gyrus, and plays a notable role in spatial navigational memory. Furthermore, optogenetic stimulation of Optoα1AR in astrocytes modulates both hippocampal synaptic excitation and inhibition. However, this modulation depends on the characteristics of the optical stimulation paradigm. Taken together, these studies provide new evidence of DBI-dependent modulation of hippocampal synaptic inhibition and behavior, and provide a new optogenetic tool to study astrocytic regulation of synaptic transmission.
Graduation Semester
2021-05
Type of Resource
Thesis
Permalink
http://hdl.handle.net/2142/110530
Copyright and License Information
Copyright 2021 Connor Courtney

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Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations - Neuroscience