Doctor of Philosophy (PhD), Wright State University, 2009, Biomedical Sciences PhD

Motoneurons are among the best studied neurons in the central nervous system. The motoneuron synapses have been well characterized in the periphery where they release acetylcholine at the neuromuscular junction. However excitatory amino acids also seem to be released from motoneuron terminals in the periphery, and centrally at their synapses contacting Renshaw cells. Although excitatory amino acids are suggested to be released from motoneuron synapses it is not known which excitatory amino acids (either aspartate or glutamate) are released, nor is the mechanism for their release known. To examine the presence and mechanism of release for aspartate and glutamate at motoneuron synapses on Renshaw cells, several immunocytochemistry experiments using both epifluorescence and electron microscopy techniques were used to determine if any of the known vesicular glutamate transporters (VGLUTs) or other transporters were present and to quantify the enrichment of aspartate and glutamate in these terminals. Moreover, immunofluorescent experiments using the Hb9::EGFP mouse model were done to confirm the specificity of VAChT immunolabeling for identifying motoneuron contacts on calbindin immunoreactive (-IR) Renshaw cells. The results from these experiments show that the known VGLUTs are not detectable at motoneuron contacts on Renshaw cells, and therefore aspartate and glutamate must be released via a VGLUT-independent mechanism. Immunofluorescent experiments with HB9::EGFP mice confirmed that VAChT is an appropriate marker for labeling motoneuron contacts on Renshaw cells. Electron microscopy experiments determined that both glutamate and aspartate are enriched in VAChT-IR contacts on Renshaw cells. Further immunofluorescent experiments looking for potential transporters for packaging excitatory amino acids into synaptic vesicles revealed that both SLC10A4 and SLC17A5 (members of the solute carrier protein family that also include the VGLUTs) were present in motoneurons. SLC10 (open full item for complete abstract)

Committee: Francisco Alvarez PhD (Advisor); Dan Halm PhD (Committee Member); Barbara Hull PhD (Committee Member); James Olson PhD (Committee Member); Robert Putnam PhD (Committee Member); Stephen Schneider PhD (Committee Member) Subjects: Anatomy and Physiology

Doctor of Philosophy in Medicinal Chemistry, University of Toledo, 2010, Medicinal Chemistry

Myasthenia gravis (MG) is characterized by autoantibody-mediated reduction of nicotinic acetylcholine receptors (AChR). In myasthenia gravis, anti-acetylcholine receptor (AChR) antibody is thought to cause damage through the activation of complement, via the classical complement pathway, in addition to causing internalization of AChRs. Interleukin-12 (IL-12), a major inducer of interferon-gamma (IFN-gamma) production, has been shown to enhance active and clinical passive experimental autoimmune myasthenia gravis (EAMG). IFN-gamma is known to be produced by various cell types, including CD4+ and CD8+ T cells, natural killer (NK) cells, and NK1.1+ T (NKT) cells. Our current research was designed to investigate the effects of IL-12 on skeletal muscle tissue. We performed passive transfer experiments with mAb D6, a mouse anti-AChR monoclonal antibody recognizing the immunodominant mouse AChR epitope, using both B6 and IFN-gamma knockout mice. The role of complement in disease induction in these mice was examined using fluorescent microscopy. When pre-treated with IL-12, B6 and IFN-gamma knockout mice had similar amounts of antibody and complement bound at the neuromuscular junction, although IFN-gamma knockout mice were resistant to EAMG development. This suggests that IL-12, through IFN-gamma, may increase susceptibility to disease through mechanisms downstream of antibody and complement binding. In order to do investigate the roles of known IFN-gamma producing cell types in passive disease enhancement, NK and NKT cells were depleted using the anti-NK1.1+ monoclonal antibody PK136 prior to administration of IL-12 and passive transfer of mAb D6 in C57BL/6 (B6) mice. Comparatively, IL-12 treatment and passive transfer of mAb D6 was performed using TCRbeta/TCRdelta dual knock-out mice (TCRbdKO mice), which possess B cells and NK cells but completely lack functional T cells and NKT cells. Interleukin-12 treatment failed to enhance passive disease in mAb PK136-treated B6 mi (open full item for complete abstract)

Committee: Katherine Wall Dr. (Committee Chair); Marcia McInerney Dr. (Committee Member); Surya Nauli Dr. (Committee Member); Francis Pizza Dr. (Committee Member) Subjects: Immunology

Master of Science, The Ohio State University, 2008, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 2006, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1966, Graduate School

Committee: Not Provided (Other) Subjects:

PHD, Kent State University, 2024, College of Arts and Sciences / School of Biomedical Sciences

Many neurochemicals that affect social behavior also play a role in mediating bone development and metabolism. In primates, higher levels of neuropeptide Y and serotonin in humans and chimpanzees, compared to monkeys, are associated with decreased levels of aggression and increased social competence, respectively. Additionally, apes have higher levels of acetylcholine (ACh) and lower levels of dopamine, corresponding to internally driven and autonomous social behavior. Humans, conversely, have relatively low ACh and high dopamine, corresponding to externally driven social behavior and social conformity. ACh is specifically associated with the control of internally versus externally motivated behaviors in the striatum and is also known to promote osteoblastogenesis, bone formation, and to also inhibit bone resorption. However, the relationship between neurochemicals in the brain, bone, and behavior has, to date, remained relatively unexplored. In this dissertation, I investigate potential relationships among ACh concentrations and bone architecture by examining rats of differing levels of domestication and also among primates. I show that, in wild-caught and laboratory-raised rats, skeletal ACh concentrations, trabecular spacing, cortical bone density, and cortical area are lower in laboratory-raised rats, while bone volume is higher. Additionally, skeletal ACh may account for 40.8% of variation in trabecular spacing and 35.5% of variation in bone volume among rats. Though the difference in skeletal ACh among groups was consistent with expectations, our other findings largely contrast with currently available literature, warranting further research into the relationship between skeletal and neural ACh. I also show that, while in a highly limited primate sample, there is no relationship between skeletal and neural ACh concentrations, the methods used to explore this relationship could be used in future studies. Lastly, I show that in exploring the relationship between (open full item for complete abstract)

Committee: Claude Owen Lovejoy (Committee Chair); Colleen Novak (Committee Member); Richard Meindl (Committee Member); Mary Ann Raghanti (Committee Member) Subjects: Anatomy and Physiology; Biology; Biomedical Research; Developmental Biology; Endocrinology; Evolution and Development; Morphology; Neurobiology; Physical Anthropology

PHD, Kent State University, 2023, College of Arts and Sciences / School of Biomedical Sciences

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by widespread cell loss and cognitive decline. However, increasing evidence suggests that sensory dysfunction may actually precede the cognitive deficits associated with the disease by years or even decades. This provides a unique opportunity for studying sensory system dysfunction as a potential biomarker for AD diagnosis and to better understand pathological mechanisms early in disease progression. The work presented in this dissertation aimed to address two unique sensory circuits. In the second chapter, the retinotectal pathway between the eye and the brain, and the primary projection cells from the retina, retinal ganglion cells, were thoroughly characterized across age and sex in 3xtg mice. Results from this study demonstrated not only significant age-related changes in several structural and functional measures in control animals, but more importantly, demonstrated that AD mice had more severe loss compared to controls. The second and third aims focused on the parabigeminal, pedunculopontine, and laterodorsal tegmental cholinergic nuclei of the brainstem and their connections to the superior colliculus, a site of multisensory integration. Results from chapter three suggest that these cholinergic nuclei do not undergo significant structural degeneration but are susceptible to AD-related pathological changes. The connectivity of these regions studied in chapter four suggested that 3xtg AD mice had reduced projections compared to control animals- which may contribute to sensory deficits reported in AD. Overall, the results of these studies provide compelling evidence for early sensory alterations in the 3xtg mouse model of AD, and additionally, that the vulnerability of sensory systems may differ throughout the brain. The results presented here provide a critical background for future studies to further address the impact of AD on sensory systems

Committee: Christine Dengler-Crish (Advisor); Matthew Smith (Committee Member); John McDaniel (Committee Member); Brett Schofield (Committee Member); Sheila Fleming (Committee Member) Subjects: Neurosciences

Master of Science in Pharmaceutical Science (MSP), University of Toledo, 2020, Pharmaceutical Sciences (Pharmacology/Toxicology)

Autosomal dominate polycystic kidney disease (ADPKD) poses a high risk for catastrophic renal cysts, hypertension, and fatal cardiac complications among afflicted patients. Due to its nature as a ciliopathy, researchers are searching the ciliary proteome for viable treatment targets.Muscarinic acetylcholine receptors (AChMRs) are widespread throughout the body and play various homeostatic roles; AChM3Rs in particular are predominately expressed in smooth muscles including the endocrine glands, vascular system, and heart. AChM3Rs also are localized to primary cilia where they play roles in cholinergic vasodilation responses; due to their localization to primary cilia, it was hypothesized that AChM3Rs are involved in the pathogenesis of ADPKD. In this study, a morpholino oligonucleotide (MO) targeting chrm3b, the zebrafish homologue to CHRM3, was used to knockdown AChM3R expression and observed the resultant phenotypes in developing embryos. Based on previous work and ADPKD zebrafish MO studies performed by others, a loss of primary cilia structure was expected to occur, resulting in multisystemic effects such as kidney cysts and cardiovascular aberrations as a result of the MO. While heart aberrations were indeed observed, along with developmental delays and increased mortality, no direct evidence that iv primary cilia were affected by the MO was observed. Nodal cilia, however, were visually absent or decentralized (scattered and few in number) within the neural tube/floorplate after injection, resulting in altered cerebrospinal fluid flow. Additionally, the disruption of neural tube nodal cilia was accompanied by a number of phenotypes including abnormal body curvature, fluid retention in the brain, kidney damage, and large gaps in the extracellular matrix between adjacent fibers in their myotome/muscle tissues. Because nodal cilia in injected groups were still present and functional elsewhere, these results imply a link between the nodal cili (open full item for complete abstract)

Committee: Wissam Aboualaiwi Dr. (Committee Chair); Williams Frederick Dr. (Committee Member); William Messer Dr. (Committee Member); Frank Hall Dr. (Committee Member) Subjects: Pharmacology

PHD, Kent State University, 2020, College of Arts and Sciences / School of Biomedical Sciences

The inferior colliculus is an auditory midbrain hub that processes both ascending and descending auditory information. Most cells within the inferior colliculus respond to sound, and for a majority of these cells, the responses can be modulated by acetylcholine. The major source of acetylcholine in the inferior colliculus comes from the pontomesencephalic tegmentum, a nucleus known for projections into the thalamus and roles in arousal and the sleep-wake cycle. Using selective viral tract tracing techniques in a ChAT-Cre Long Evans rat, we characterize the distribution of cholinergic inputs from the pontomesencephalic tegmentum to all subdivisions of the inferior colliculus and associated intercollicular nuclei. We find evidence of cholinergic inputs onto both glutamatergic and GABAergic inferior colliculus neurons. In a separate set of experiments, we seek to determine if acetylcholine modulates major inferior colliculus output pathways. Using retrograde tract tracing techniques in combination with immunohistochemistry, we determine if cholinergic boutons make synaptic contact with inferior colliculus neurons that project to the medial geniculate, cochlear nucleus, or superior olivary complex. In these experiments, we find cholinergic contacts onto GABAergic and glutamatergic inferior colliculus neurons that project to the medial geniculate, as well as cholinergic contacts onto glutamatergic inferior colliculus neurons that project to the cochlear nucleus or superior olivary complex. We found cholinergic contacts onto neurons that participate in these output pathways in all inferior colliculus subdivisions and associated intercollicular nuclei. Taken together, we show an extensive network of cholinergic inputs that modulates a wide variety of auditory and multisensory functions of the inferior colliculus.

Committee: Brett Schofield (Committee Chair); Jeffrey Wenstrup (Committee Member); Rebecca German (Committee Member); Samuel Crish (Committee Member); Sean Veney (Committee Member) Subjects: Biology; Biomedical Research; Neurosciences

Master of Science, The Ohio State University, 2019, Vision Science

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express melanopsin, a Gq-coupled photopigment, and these neurons exhibit sustained action potential firing in response to light. ipRGCs have primarily non-visual functions, including an influence on the pupillary light reflex (PLR) to which they contribute to sustained pupil constriction. Acetylcholine is released in the retina by starburst amacrine cells in response to retinal image motion, and can be stimulated by flickering light and moving gratings. Light with a flicker frequency range of 3-10 Hz, peaking near 6 Hz, is especially effective at evoking retinal acetylcholine release. It has been previously demonstrated that rat ipRGCs fire sustained action potentials in response to cholinergic agonists. Sustained ipRGC spiking was also evoked by 6 Hz flickering light, presented at an irradiance below melanopsin's activation threshold, mediated by a muscarinic acetylcholine receptor-mediated pathway. The purpose of this study is to evaluate human pupil responses during and after exposure to light of differing frequencies, hypothesizing that a 6 Hz flickering light will cause more sustained pupil constriction than other frequencies. Seven healthy subjects were exposed to blue (480 nm) and red (620 nm) light at different irradiances (1012 and 1010 photons/s/cm2) and frequencies (0, 0.1, 6 and 30 Hz) for five minutes. Light was presented to the dilated left pupil; the consensual response of the right pupil was recorded. Pupil constriction was normalized and compared amongst the different flicker frequencies within each wavelength and irradiance level. Pupil constriction during light exposure and pupil dilation after light offset were analyzed. For blue light at 1012 photons/s/cm2, the 6 Hz and 0.1 Hz light stimuli produced greater overall pupil constriction compared to the 30 Hz stimulus. For red light at 1012 photons/s/cm2, the 6 Hz and 0.1 Hz stimuli elicited greater overall pupil constriction relativ (open full item for complete abstract)

Committee: Andrew Hartwick OD, PhD (Advisor); Michael Earley OD, PhD (Committee Member); Donald Mutti OD, PhD (Committee Member) Subjects: Biochemistry; Neurobiology; Ophthalmology; Physiology

Doctor of Philosophy, Case Western Reserve University, 2018, Neurosciences

The striatum serves as the main integration point for the basal ganglia circuit, which is critical for driving reward, movement, and associative behaviors. While these basal ganglia inputs drive changes in striatal output, cholinergic interneurons are also strong modulators of striatal activity. These cells are thought to be important for behavioral flexibility and striatal-dependent learning. Cholinergic interneurons modulate medium spiny neurons, the sole striatal output neuron, through multiple circuits. However, acetylcholine in this region activates receptors resulting in G-protein coupled receptor mediated modulation of medium spiny neurons. Due to the slow, multistep nature of G-protein coupled receptors and the lack of rapid acetylcholine measurement techniques, it has been challenging to investigate striatal acetylcholine transmission. The objective of this work was to examine nicotinic receptor-mediated dopamine release and D2 dopamine receptor activity as well as muscarinic M4 receptor activity on medium spiny neurons to determine the mechanisms of acetylcholine release in the striatum. This work used a combination of viral-mediated gene transfer, electrophysiology, optogenetics, and immunohistochemical and 2-photon imaging to examine acetylcholine signaling in this region. First, I used viral overexpression of a G-protein inwardly rectifying potassium channel in medium spiny neurons to measure D2 receptor activity in the context of nicotinic-mediated dopamine release. I found that, although synchronous cholinergic interneuron firing is sufficient to drive dopamine release and subsequent D2 receptor activation, acetylcholine release does not modulate direct dopamine release from dopamine terminals. Next, I examined direct synaptic acetylcholine release at muscarinic synapses. I found, for the first time, that muscarinic receptors on medium spiny neurons could encode single action potentials and physiological firing patterns in cholinergic interneurons, th (open full item for complete abstract)

Committee: Christopher Ford (Advisor) Subjects: Neurobiology; Neurosciences

MA, Kent State University, 2017, College of Arts and Sciences / Department of Psychological Sciences

Rats have the capacity to extrapolate a known sequence of events to anticipate a novel item. We examined whether or not rats can extrapolate a serial pattern during a muscarinic cholinergic challenge. Adult male and female rats learned to nosepoke a sequential pattern of responses in a circular array of 8 receptacles attached one each to the walls of an octagonal chamber. This training pattern consisted of seven 3-element chunks of a rule-based serial pattern, namely, 123-234-345-456-567-678-781. On the day after meeting a high criterion on the training pattern, rats were given i.p. injections of 0.6 mg/kg scopolamine hydrobromide, a muscarinic cholinergic blocker, before encountering patterns consisting of the 7-chunk training pattern plus an added eighth chunk. The added chunk was either consistent with pattern structure (chunk “812”) or contained a terminal element that violated pattern structure (chunk “818”, where the violation element is underlined). Under scopolamine, and even while showing scopolamine-induced impairments of performance throughout the pattern, rats in both groups extrapolated known pattern structure in the novel added chunk, producing approximately 60% rule-consistent “2” responses on the terminal element of both types of chunks. Thus, despite scopolamine exposure, both male and female rats extrapolated well-learned pattern structure to a new chunk. Whereas earlier work showed that muscarinic cholinergic suppression had little effect on rule learning during acquisition of a pattern, the current study demonstrated that intact muscarinic cholinergic neurotransmission is not necessary for extrapolation of a well-learned rule to a novel chunk.

Committee: Stephen Fountain (Advisor); David Riccio (Committee Member); Aaron Jasnow (Committee Member); Beth Wildman (Committee Member) Subjects: Animal Sciences; Animals; Behavioral Sciences; Behaviorial Sciences; Neurosciences; Psychobiology; Psychology

Master of Science (MS), University of Toledo, 2017, Pharmaceutical Sciences (Pharmacology/Toxicology)

Primary endothelial cilia are microtubule-based organelles that act as mechano-sensors to help detect and respond to changes in the extracellular environment. One of these responses includes its ability to detect fluid flow and blood pressure, and translating that signal into a biochemical process to synthesize nitric oxide, an endogenous vasodilator. Abnormal cilia structure and function have been known to cause a myriad of human disorders, including polycystic kidney disease (PKD) and hypertension. It is also well documented that the acetylcholine muscarinic 1 receptor (AChM1R) plays a key role in producing a vasodilation response in the vasculature. However, much remains to be learned about the relationship between primary endothelial cilia and AChM1R. To understand more about the relationship between AChM1R and the mechano-sensory function of primary cilia, the effects of muscarinic modulators on cilia length and function in wild-type, and mechano-insensitive cilia mutant endothelial cells, Pkd1-/- (dysfunctional cilia) and Tg737orpk/orpk (cilia-less) were examined. We show that AChM1R localizes to primary endothelial cilia. AChM1R activation leads to a significant increase in cilia length in endothelial cells treated with CDD102A, an AChM1R agonist, compared to non-treated cells (1.21 ± 0.07µm vs. 2.33 ± 0.04µm for wild-type, 1.02 ± 0.01µm vs. 1.44 ± 0.01µm iv for Pkd1-/-, and 0.024 ± 0.005µm vs. 0.3 ± 0.004µm for Tg737orpk/orpk). Treating endothelial cells with pirenzepine, an AChM1R antagonist, led to a significant decrease in cilia length compared to non-treated cells (1.34 ± 0.02µm vs. 1.15 ± 0.01µm in wild-type, and 1.16 ± 0.01µm vs. 0.71 ± 0.01µm in Pkd1-/-). Treatment with CDD102A also significantly upregulated expression of AChM1R and phosphorylated eNOS. The data gathered from these experiments demonstrate an effect of AChM1R on cilia structure and function, and potentially their role in PKD and hypertension.

Committee: Wissam AbouAlaiwi (Committee Chair); William Messer (Committee Member); Caren Steinmiller (Committee Member) Subjects: Pharmacology

Doctor of Philosophy, The Ohio State University, 2017, Chemistry

The purpose of this dissertation is to highlight three unique approaches towards discovering a catalytic treatment towards organophosphorus (OP) poisoning. All three potential approaches focus on developing catalytic treatment methods that focus on hydrolyzing OP nerve agents before they can inhibit acetylcholinesterase (AChE). AChE is a serine hydrolase which is responsible for hydrolyzing the neurotransmitter acetylcholine (ACh). AChE operates near diffusion control and can hydrolyze upwards of 25,000 ACh molecules every second. However, when AChE is inhibited by a nerve agent, an excess amount of ACh will build up at neurosynaptic gaps, thereby causing a cholinergic crisis. Once this occurs, a person will start to develop symptoms of muscle contractions, blurry vision, seizures and/or respiratory failure. An OP nerve agent has this effect because it is a structural analog to ACh; however, phosphylation of the active site is more difficult to reverse. Reactivation of AChE can occur by hydrolyzing the phosphylated enzyme with a nucleophile such as 2-PAM (often administered after OP exposure has occurred). Unfortunately, if this reactivation does not occur, the phosphylated enzyme will undergo a spontaneous dealkylation step (termed aging) to give a “dead” enzyme, which to date cannot be reactivated. The first therapeutic design focuses on the research and development of phosphorane haptens. These haptens are conjugated to some mutagen and administered into mice. This causes an immune response and can generate catalytic antibodies which are capable of hydrolyzing the nerve agent VX. In total, ten different haptens were synthesized, mimicking the hydrolysis transition state of VX, and all generated specific antibodies. Each titer of antibodies were then tested against authentic VX samples. The second approach focuses on the development of a combinatorial approach to synthesizing a random library of cyclic peptides. These cyclic peptides are meant to model the activ (open full item for complete abstract)

Committee: Christopher Hadad (Advisor); Jon Parquette (Committee Member); Psaras McGrier (Committee Member) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 1981, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1977, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1974, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1968, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

MA, Kent State University, 2015, College of Arts and Sciences / Department of Anthropology

Cholinergic innervation of the basal ganglia is important in learning and memory, and striatal cholinergic neurons have been implicated in the integration of cognitive and motivational states with behavior. Further, deficits in acetylcholine have been correlated with loss of cognitive function in Alzheimer's disease and schizophrenia. These lines of evidence suggest a potentially important role for this subcortical innervation in the evolution of human cognitive functions. The present study quantified axons and interneurons immunoreactive for choline acetyltransferase (ChAT) in regions of the executive and motor loops of the basal ganglia of humans, great apes (chimpanzee and gorilla), Old World monkeys (macaque and baboon), and one New World monkey (capuchin). Stereologic methods were used to quantify ChAT-ir axon length density to neuron density (ALv/Nv) and the percentage of cholinergic neurons in striatal regions. Interestingly, humans did not possess the highest or lowest density of cholinergic innervation, as expressed by axons or neurons. The phylogenetic differences observed were unexpected and indicated that a relative increase in cholinergic innervation was not required to support human cognitive abilities.

Committee: Mary Ann Raghanti Dr. (Advisor); Richard Meindl Dr. (Committee Member); Linda Spurlock Dr. (Committee Member) Subjects: Comparative; Evolution and Development; Neurosciences

Doctor of Philosophy, The Ohio State University, 2015, Neuroscience Graduate Studies Program

Intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a rare subset of ganglion cells in the mammalian retina that are primarily involved in non-image forming (NIF) visual processes. In the presence of light, ipRGC photoreceptors exhibit sustained depolarization, in contrast to the transient hyperpolarizing responses of rod and cone photoreceptors. The persistence of this response with light offset underlies the reduced temporal resolution exhibited by these ipRGCs. The overall aim of this thesis was to determine whether the unique temporal dynamics of ipRGC photoresponses are subject to modification by endogenous retinal neuromodulators. As post-synaptic photoreceptors, ipRGCs are capable of integrating photic information transmitted from pre-synaptic neurons regulated by rod- and cone-driven signaling. Given that ipRGCs possess dense dendritic nets that span the entire retina, I hypothesized that these ganglion cell photoreceptors were capable of being modulated by extrinsic input from the retinal network. Using multi-electrode array recordings on rat retinas, I demonstrated that the duration of light-evoked ipRGC spiking can be modified through an intracellular cAMP/PKA-mediated signaling pathway. Specifically, stimulation of the cAMP/PKA pathway leads to prolonged ipRGC light responses. Expanding upon these findings, I next identified an endogenous retinal neuromodulator capable of modulating ipRGC photoresponses through this signaling pathway. I demonstrated that the retinal neuromodulator adenosine suppressed light-evoked ipRGC spiking through activation of the Gi-coupled A1 receptor. These receptors were expressed by ipRGCs themselves, as confirmed using immunohistochemistry and calcium imaging experiments on dissociated ipRGCs. Notably, I show that endogenous adenosine A1-mediated suppression of ipRGC photoresponses can occur during dark-adapted conditions, consistent with an elevation in retinal adenosine levels after maintenance in the dark (open full item for complete abstract)

Committee: Andrew Hartwick (Advisor); Karl Obrietan (Committee Member); Stuart Mangel (Committee Member); Heather Chandler (Committee Member) Subjects: Neurosciences