Doctor of Philosophy, The Ohio State University, 2024, Neuroscience Graduate Studies Program

Women are over twice as likely to develop stress-induced affective disorders, including anxiety disorders and major depressive disorder, than men, however this sex difference in prevalence does not emerge until pubertal onset. This suggests that there may be a role for ovarian hormones in organizing stress-sensitive brain circuitry during adolescence to increase female vulnerability to stress. Our lab had previously identified female prefrontal parvalbumin (PV) interneurons as sensitive to stress in a sex-specific manner, with increased expression and activation of prefrontal PV+ cells being associated with increased anxiety-like behavior following four weeks of chronic stress. Furthermore, we have found that activation of PV+ interneurons in the absence of stress is sufficient to induce anxiety-like behavior in female, but not male, mice, however the mechanism underlying this sex-specific stress sensitivity remained unknown. In this work, I aimed to characterize the mechanism modulating the sexual dimorphism of prefrontal parvalbumin (PV) interneuron stress sensitivity; and determine whether ovarian hormones at puberty contributed to the maturation of prefrontal PV+ interneurons and their stress-sensitive phenotype. First, we investigated whether the stress-sensitive phenotype of female prefrontal PV+ interneurons could be induced in male mice using a longer period of chronic stress or chemogenetic activation of this cell population. While exposure to a longer period of unpredictable chronic mild stress did lead to stress-induced increases in anxiety-like behavior in male mice, this outcome could not be achieved by directly stimulating prefrontal PV+ interneurons, suggesting that the stress sensitivity of prefrontal PV+ interneurons in females and associated increased anxiety-like behavior cannot be induced and is instead unique to females. Next, we aimed to determine the functional relevance of pubertal ovarian hormones in driving stress sen (open full item for complete abstract)

Committee: Laurence Coutellier (Advisor) Subjects: Neurosciences

Master of Science (MS), Wright State University, 2021, Physiology and Neuroscience

Proprioceptive sensory neurons encode critical mechanosensory information that helps determine how the body interacts with the outside world and monitors the proper execution of motor movements. Housed in skeletal muscles lie specialized mechanoreceptors that are critical to this feedback loop: muscle spindles supplied by group Ia & group II afferents, and Golgi tendon organs supplied by group Ib afferents relay information regarding changes in muscle force, length, and tension. All three afferent subtypes originate in the muscle and travel to the dorsal root ganglia, relaying information to the central nervous system. GTO and MS proprioceptive afferent subtypes have been identified, traced, and labeled by restrictive RNA and DNA sequencing techniques that eliminate the potential for in vivo and ex vivo analysis. To confirm the identity of different proprioceptive afferent subtypes in the dorsal root ganglia of mice, the present study developed a method of fluorescence tracing using a dextran dye to trace afferents and their origins. By injecting tetramethylrhodamine dextran dye directly into the quadriceps muscle, the muscle spindle proprioceptive afferents selectively transport the dye to the cell body in the DRG demonstrating its origin and classification. Being able to selectively label and trace muscle spindle afferents allows us to accurately collect data on the cells in the DRGs.

Committee: David R. Ladle Ph.D. (Advisor); Mark M. Rich M.D., Ph.D. (Committee Member); Patrick M. Sonner Ph.D. (Committee Member) Subjects: Neurobiology; Neurosciences; Physiology

Master of Science (MS), Wright State University, 2020, Anatomy

Proprioception is a sensory modality that conveys information regarding the body's movement and position in three-dimensional space. The sensory afferent fibers responsible for this modality, proprioceptors, are a special subtype of mechanoreceptors, the sensory afferent family responsible for movement sensing. It has been shown that proprioceptive neurons undergo several physiological changes after peripheral nerve injury, including perhaps changes in gene expression. In this study, we design riboprobes to use for in situ hybridization to detect two proprioceptive genetic markers, Parvalbumin and Nxph1 in mouse dorsal root ganglia. Tissue samples were prepared from three animal conditions, adult control, sham surgery, and sciatic nerve transection injury. We were successfully able to design the riboprobes needed for specific staining and monitored expression patterns in each condition. Results showed inconclusive staining for the sham surgery and transection injury controls for Nxph1, whereas Parvalbumin showed a reduced, but continued expression after nerve injury.

Committee: David R. Ladle Ph.D. (Advisor); Patrick M. Sonner Ph.D. (Committee Member); Mark M. Rich M.D., Ph.D. (Committee Member) Subjects: Nanoscience

Doctor of Philosophy (PhD), Wright State University, 2011, Biomedical Sciences PhD

Locomotor development is dependent on the maturation of spinal cord circuits controlling motor output, but little is known about the development of the spinal interneurons that control motoneuron activity. This study focused on the development of Renshaw cells (RCs) and Ia inhibitory interneurons (IaINs), which mediate recurrent and reciprocal inhibition, respectively, two basic inhibitory circuits for motorneuron control. Both interneurons originate from the same progenitor pool (p1) giving rise to ventral spinal embryonic interneurons denominated V1. V1-derived interneurons (V1-INs) establish local inhibitory connections with ipsilateral motoneurons and express the transcription factor engrailed-1. This characteristic permitted the generation of transgenic mice that were used in this study to genetically label V1 interneuron lineages from embryo to adult. Adult V1-derived Renshaw cells and IaINs share some similar properties, both being inhibitory and establishing ipsilateral connections; but differ in morphology, location in relation to motor pools, expression of calcium binding proteins (calbindin vs. parvabumin), synaptic connectivity and function. These differences are already present in neonates, therefore the purpose of this study was to determine possible embryonic differentiation mechanisms. Using 5‟-bromodeoxyuridine birth-dating we demonstrated that V1-INs can be divided into early and late born groups. The early group quickly upregulates calbindin iv expression and includes the Renshaw cells, which maintain calbindin expression through life. The second group includes many cells that postnatally upregulate parvalbumin, including IaINs. This later born group is characterized by upregulation of the transcription factor FoxP2 as they start to differentiate and is retained up to the first postnatal week in many V1-derived IaINs. In contrast, Renshaw cells express the transcription factor MafB that seems relatively specific to them within the V1-INs. Furtherm (open full item for complete abstract)

Committee: Francisco Alvarez PhD (Advisor); Paula Bubulya PhD (Committee Member); Timothy Cope PhD (Committee Member); David Ladle PhD (Committee Member); James Olson PhD (Committee Member) Subjects: Neurology

Master of Science (MS), Wright State University, 2010, Anatomy

These experiments analyze differences in synaptic development in central auditory pathways between normal hearing (CBA/J) and congenitally deaf (dn/dn) mice, which provide valuable insight into central synaptic plasticity corresponding to human congenital deafness. Immunofluorescent analysis of the developmental expression of the calcium buffering proteins calretinin, calbindin d-28k, and parvalbumin at various postnatal time points was performed to assess the effects of altered neural activity on the level and/or pattern of protein expression within these nuclei. Results indicate that the pattern of calbindin and parvalbumin is unaffected by congenital deafness in dn/dn mice. However, the pattern of calretinin expression in the MNTB during development of dn/dn mice differed significantly from that of CBA/J mice, indicating that calcium buffering may be impaired in these synapses without appropriate afferent stimulation.

Committee: Robert E.W. Fyffe Ph.D. (Advisor); Larry J. Ream Ph.D. (Committee Member); John C. Pearson Ph.D. (Committee Member) Subjects: Biomedical Research; Neurology

Master of Science (MS), Wright State University, 2006, Anatomy

This experiment analyzes synaptic differences in the central auditory pathway between normal hearing and congenitally deaf (dn/dn) mice, and provides valuable insight into central changes that correspond with human congenital deafness. Specifically, this experiment analyzes developmental expression of the Calcium (Ca2+)-binding proteins Calretinin (CR), Calbindin D-28k (CB) and Parvalbumin (PV) in large excitatory synapses in the anteroventral cochlear nucleus (AVCN) and the medial nucleus of the trapezoid body (MNTB) of normal and dn/dn mice. Immunofluorescence imaging with primary antibodies detecting CR, CB or PV was used to analyze the expression of each at 9 days, 13 days, 20 days, 30 days and 49 days postnatal in normal and dn/dn mice. Results indicated that Ca2+-binding expression was similar at each location in normal and dn/dn mice at 9 days postnatal, prior to opening of the ear canal and the onset of hearing (which occurs around 11 days postnatal) . In normal mice, patterns of Ca2+-binding protein expression changed progressively after the onset of hearing. In dn/dn mice (which completely lack auditory nerve activity), however, patterns of expression did not change after the onset of hearing, suggesting that patterns of Ca2+-binding protein expression change during development in normal mice in response to evoked auditory nerve activity, and that patterns of Ca2+-binding protein expression do not change during development in dn/dn mice due to lack of evoked auditory nerve activity. As a result, Ca2+ buffering is impaired in synapses located in the AVCN and MNTB of dn/dn mice.

Committee: Robert Fyffe (Advisor) Subjects: