Date of Award

1-1-2021

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Psychology

Program

Behavioral Neuroscience

Content Description

1 online resource (iii, 148 pages) : illustrations (some color)

Dissertation/Thesis Chair

Christine K Wagner

Committee Members

Damian Zuloaga , Bruce Svare, Erin Bell

Keywords

Attention, Dopamine, Medial Prefrontal Cortex, Microglia, Progestins, Synapse, Hydroxyprogesterone, Progesterone, Dopaminergic mechanisms, Psychophysiology, Developmental neurophysiology

Subject Categories

Neuroscience and Neurobiology

Abstract

This dissertation examined the complex developmental impact of the clinically relevant synthetic progestin 17α-hydroxyprogesterone caproate (17-OHPC) on medial prefrontal cortex (mPFC) development. In rodents, the effects of 17-OHPC are subtle, but significant. In the Chapter II, we observed that 17-OHPC abolishes sex differences in dopaminergic fiber innervation and alters microglia phenotype in the prelimbic and infralimbic areas by the end of the first postnatal week. In the third chapter, the overall effect of 17-OHPC on the ontogeny of dopaminergic fiber innervation and synaptic bouton density were used to characterize the timing and duration of treatment effects in the mPFC. In the fourth chapter, the effect of 17-OHPC on attention was assessed using the modified signal detection task, which resulted in an unexpected but highly consistent behavior of response omissions, indicating that a particular facet of attention processing was altered. Finally, an opportune collaboration with access to human data allowed for basic comparisons in child development between progestin exposed and nonexposed children, with results indicating specific areas of developmental delay. Together, the findings presented in this dissertation help inform specific risks associated with developmental exposure to 17-OHPC. Specifically, 17-OHPC may disrupt the timing and connectivity of dopaminergic fiber innervation of the mPFC and likely affects other afferents arriving to the mPFC. The findings in this document highlight the tremendous gap in understanding how a hormonal treatment in clinical use can disrupt the development of critical neural pathways with high specificity.

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