D3 receptor and β-Arrestin2 modulation of spiny projection neuron intrinsic excitability

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dc.contributor.advisorPaladini, Carlos A.
dc.contributor.authorPetko, Alyssa Kirstin
dc.contributor.committeeMemberApicella, Alfonso
dc.contributor.committeeMemberWilson, Charles J.
dc.contributor.committeeMemberTroyer, Todd
dc.contributor.committeeMemberWeinshenker, David
dc.creator.orcidhttps://orcid.org/0000-0003-0772-838X
dc.date.accessioned2024-02-12T19:30:29Z
dc.date.available2021-05-16
dc.date.available2024-02-12T19:30:29Z
dc.date.issued2019
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractThe nucleus accumbens (NAc) is a critical node of the mesolimbic DA system that regulates drug-induced behaviors. Spiny projection neurons (SPNs) make up 95% of the neurons in the NAc, and are subdivided into two populations, D1 and D2 expressing. Each subpopulation also expresses D3 receptors, and μ opioid receptors, which have also been shown to be critical components in reward related behavior. Nucleus accumbens dopamine and μ receptors are G-protein coupled receptors that are coupled to β-Arrestin2 (βarr2), which is involved in receptor desensitization, but also activates signaling cascades independent of conventional G-protein dependent signaling. The purpose of my thesis work is to 1) Determine if inhibition of D3 receptors alters dopamine-induced changes in D1 or D2 SPN neuronal excitability and 2) uncover the role of βarr2 in dopamine- and morphine- induced excitability changes in D1 and D2 SPNs. In order to address these questions, I employed the use of pharmacology, slice electrophysiology, transgenic mouse models, and behavior assays. I had found that D3 antagonism enhances dopamine-induced excitability in D1, but not D2 SPNs, suggesting that D3 receptors act to dampen neuronal excitability during periods of dopamine release. Next, I showed that βarr2 modulates dopamine and morphine -induced changes in excitability in D2, but not D1 SPNs, which suggests that βarr2 mediates cellular excitability in separate populations of neurons. Overall, this work demonstrates a unique and separate role for D3 receptors and βarr2 in modulating D1 and D2 SPNs cellular excitability.
dc.description.departmentIntegrative Biology
dc.format.extent86 pages
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12588/4908
dc.languageen
dc.subjectBeta-Arrestin2
dc.subjectD3 receptors
dc.subjectDopamine
dc.subjectMorphine
dc.subjectNucleus Accumbens
dc.subjectSpiny Projection Neurons
dc.subject.classificationNeurosciences
dc.subject.classificationPharmacology
dc.titleD3 receptor and β-Arrestin2 modulation of spiny projection neuron intrinsic excitability
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentIntegrative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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