Nutrient restriction is a relatively common production insult to pregnancy in cattle. Recently, melatonin supplementation has been investigated as a possible therapeutic to rescue the negative effects of nutrient restriction. Neurotransmitters have been implicated as having negative programming effects in mouse and human pregnancies, manifested as metabolic and neurologic disorders. The role of neurotransmitters in fetal development has only begun to be understood in mice and humans. Neurotransmitters have not been analyzed in cattle, much less within the context of a compromised pregnancy. Brangus heifers were allotted to one of four treatments (ADQ-CON, RES-CON, ADQ-MEL, RES-MEL) in either Fall 2019 or Summer 2020. Cesarian sections, at day 240 of gestation, allowed for fetal and placental tissues to be collected for neurotransmitter and gene expression analysis. Alterations to neurotransmitter pathways were observed in a seasonally dependent manner. Future investigation is needed into the implications of altered neurotransmitters on post-natal life.

Serotonin (5-hydroxytryptamine, 5-HT), considered to be a synaptic transmitter within the central nervous system, has been shown to be localized mainly in the paleocortex of the brain. Others have shown disturbances of normal 5-HT metabolism to be associated with mental illness and disease. Attempts to inject tritium labelled 5-HT into cerebrospinal fluid of the rat brain for anatomical localization studies were·made. The following observations were noted, (1) there exists a perivascular space in which fluid flows and distribution is relatively uninhibited as compared to subarachnoid space, (2) the labelled 5-HT penetration of brain tissue parenchyma is restricted and radioactivity is attenuated going away from the surface of access, and (3) the injected labelled 5-HT is absorbed into areas believed to contain true serotonergic fibers, especially throughout the paleocortex. Suggestions concerning the anatomical importance of the perivascular space observed are made. Also comparisons of 5-HT brain localization with metabolism and physiology of 5-HT are made in relation to mental illness.

Drosophila melanogaster is an attractive model organism for the study of numerous fundamental processes including nervous system development and function. This is due to the power of Drosophila genetics combined with the high degree of similarity between this organism and vertebrate systems, not only at the molecular level but also at the cellular and behavioural levels. The first part of my thesis focused on trophic interactions occurring in Drosophila larval central nervous system. Specifically, it describes the interaction of serotonin (5HT)-producing neurons with other three groups of neurons: the larval photoreceptors expressing Rhodopsin 5 (Rh5), the photoreceptor subset expressing Rhodopsin 6 (Rh6), and the larval circadian pacemakers (LNv). I found that both Rh5-and Rh6-expressing fibers contact a 5-HT arborization in the larval optic neuropil, where the 5-HT processes also overlaps with the dendrites of the LNv. The results of my experiments also indicate that the Rh6-expressing terminus is the neural process providing the signal required for the outgrowth of the serotonergic arborization. Furthermore, proper branching of this arborization requires normal Rae function. These findings further support the importance of extrinsic and intrinsic signalling for the assembly ofthe nervous system. The remainder of my studies attempted to investigate candidate neurons modulating Drosophila larval photobehaviour. Using the larval response to light as a behavioural paradigm and neuronal silencing experiments, my results demonstrate that 5HT neurons located in the brain regulate the larval photoresponse during development. In addition, my findings suggest that this modulation occurs at a central level and that is mediated by 5-HT1A(Dro) receptors. These observations provide new insights into the functions of serotonergic neurons in Drosophila as well as how neuromodulators shape neuronal circuit function and ultimately behaviour. / Thesis / Doctor of Philosophy (PhD)

Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter of the central and peripheral nervous systems, predominantly secreted in the gastrointestinal tract, especially in the gut. 5-HT is a crucial enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. Gastroenteropathy is one of the most clinical problems in diabetic patients with frequent episodes of hyperglycemia. Changes in 5-HT expression may mediate gastrointestinal tract disturbances seen in diabetes, such as nausea and diarrhea. Based on the double immunohistochemical staining, this study determined the variability in the population of 5-HT-positive neurons in the porcine small intestinal enteric neurons in the course of streptozotocininduced diabetes. The results show changes in the number of 5-HT-positive neurons in the examined intestinal sections. The greatest changes were observed in the jejunum, particularly within the myenteric plexus. In the ileum, both de novo 5-HT synthesis in the inner submucosal plexus neurons and an increase in the number of neurons in the outer submucosal plexus were noted. The changes observed in the duodenum were also increasing in nature. The results of the current study confirm the previous observations concerning the involvement of 5-HT in inflammatory processes, and an increase in the number of 5-HT -positive neurons may also be a result of increased concentration of the 5-HT in the gastrointestinal tract wall and affects the motor and secretory processes, which are particularly intense in the small intestines.

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