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

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2021

Author dc:creator

• Courtney, Connor Duke

Contributors dc:contributor

• Christian-Hinman, Catherine A
• Rhodes, Justin S
• Sweedler, Jonathan V
• Tsai, Nien-Pei

• diazepam binding inhibitor
• astrocyte
• synaptic transmission
• hippocampus

Statement dc:rights

• Copyright 2021 Connor Courtney

Language dc:language

en

Handle dc:identifier

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

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/110530