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You searched for +publisher:"University of North Carolina" +contributor:("Berrios, Janet"). One record found.

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University of North Carolina

1. Berrios, Janet. Maternal Ube3a is Required for Neurotypical Motivational Drive and GABA co-release.

Degree: 2015, University of North Carolina

Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are known to be critical players in motivated, reward-seeking behaviors and are involved in learning processes during positive-reinforcement. These neurons co-release several neurotransmitters in the NAc, however; their differential role in motivation and positive-reinforcement is unknown. Angelman syndrome (AS) is a neurodevelopmental disorder caused by the deletion or mutation of the E3-ubiquitin ligase, Ube3a. Ube3a is monoallelically expressed from the maternal allele and is paternally imprinted in a tissue specific manner. Mouse models of AS have been shown to have dopaminergic related phenotypes such as ataxia and decreased brain stimulation reward (BSR) threshold. This decrease in BSR is thought to be mediated, in part, by an increase in dopamine release within the NAc as evidenced within AS model mice using electrically mediated BSR. Because of this increase in dopamine release within the NAc, we hypothesized that VTA-to-NAc projections were hyperexcitable leading to dopaminergic dysregulation. We used a combinatorial approach of in vivo and in vitro optogenetics to determine if dopaminergic projections from the VTA-to-NAc were specifically driving an increase in motivational drive and dopamine release. Using circuit-specific manipulations, we found that there was not a change in dopamine release in AS model mice, but that there was a significant increase in motivational drive to self-stimulate these VTA axons in the NAc using a 1:1 fixed ratio operant task. Next, we determined if Ube3a is required for neurotypical motivational drive using a novel conditional deletion mouse model (Ube3aFLOX/p+) in which Ube3a was deleted from tyrosine hydroxylase (TH) positive neurons. We found that upon conditional Ube3a deletion, dopamine release remained at similar levels to wildtype mice however, motivational drive was significantly increased to a similar degree as in AS model mice. We then hypothesized that the change in motivational drive was mediated by GABA or glutamate co-release. Previously, an inhibitory imbalance phenotype was found in AS model mice in which they have a decrease in inhibitory drive. We used in vitro optogenetics in conjunction with electrophysiology to determine if GABA and glutamate co-release was affected when Ube3a is specifically ablated in TH positive neurons. We found that GABA co-release was severely compromised when Ube3a is ablated but glutamate co-release was unaffected. We also found that these phenotypes can be rescued upon exogenous expression of VGAT, a vesicular GABA transporter. Here, we suggest a novel role for GABA co-release in VTA-to-NAc terminals in a mouse model for Angelman syndrome. Using in vivo and in vitro optogenetic combinatorial approaches, our findings suggest a new utility for the E3-ubiqutin ligase, Ube3a, in inhibitory transmission from dopaminergic fibers in the ventral striatum. Advisors/Committee Members: Berrios, Janet, Kash, Thomas, Philpot, Benjamin, Robinson, Donita, Stuber, Garret, Manis, Paul B..

Subjects/Keywords: Neurosciences; Biology; Behaviorism (Psychology); School of Medicine; UNC Neuroscience Center; Neuroscience Curriculum

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APA (6th Edition):

Berrios, J. (2015). Maternal Ube3a is Required for Neurotypical Motivational Drive and GABA co-release. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:21f5b75d-a0d8-4fb1-8a45-06afb0fcd26f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Berrios, Janet. “Maternal Ube3a is Required for Neurotypical Motivational Drive and GABA co-release.” 2015. Thesis, University of North Carolina. Accessed December 05, 2020. https://cdr.lib.unc.edu/record/uuid:21f5b75d-a0d8-4fb1-8a45-06afb0fcd26f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Berrios, Janet. “Maternal Ube3a is Required for Neurotypical Motivational Drive and GABA co-release.” 2015. Web. 05 Dec 2020.

Vancouver:

Berrios J. Maternal Ube3a is Required for Neurotypical Motivational Drive and GABA co-release. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2020 Dec 05]. Available from: https://cdr.lib.unc.edu/record/uuid:21f5b75d-a0d8-4fb1-8a45-06afb0fcd26f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Berrios J. Maternal Ube3a is Required for Neurotypical Motivational Drive and GABA co-release. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:21f5b75d-a0d8-4fb1-8a45-06afb0fcd26f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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