No description available.

Noncholinergic neurotransmission was studied in vitro in the guinea pig inferior mesenteric ganglion (IMG) using the technique of intracellular recording. First, the role of substance P (SP) in noncholinergic transmission was examined. Forty-four percent of IMG neurons depolarized upon superfusion of SP (1-10 x 10⁻⁷M); however, some neurons that were insensitive to SP still exhibited slow excitatory potentials (EPSPs) in response to nerve stimulation. During exposure to SP, slow EPSPs were depressed by 52% compared to paired control EPSPs. In animals treated with systemic doses of capsaicin (50-350 mg/kg), mean slow EPSP amplitude was 3.5 mV compared to 6.8 mV in untreated animals. Arginine-vasopressin (AVP) was tested for its electrophysiological effects on IMG neurons and synaptic transmission. AVP (0.5-10 x 10⁻⁷M) produced a depolarization in 67% of neurons, accompanied by an increase in membrane resistance of 44%. The depolarizations and increase in resistance were blocked by a specific V₁ receptor antagonist. During AVP-induced depolarizations, slow EPSPs were reversibly depressed in the majority of neurons by a mean of 71% relative to paired control EPSPs. The V₁ antagonist blocked slow EPSPs in only 10% of neurons tested. A group of neurons exhibiting slow EPSPs was exposed separately to both AVP and SP. Some neurons were exclusively sensitive to either SP or AVP, others were sensitive to both peptides, and still others were sensitive to neither peptide. The physiologic role of noncholinergic transmission was examined using a preparation consisting of a segment of distal colon attached to the IMG. Distension of the colon segment produced a slow depolarization resistant to cholinergic antagonists in 44% of IMG neurons. Distension-induced noncholinergic depolarizations increased in amplitude with colonic intraluminal pressure and with membrane hyperpolarization, and were accompanied by an increase in membrane input resistance of 21%. Capsaicin in vivo reduced the number of neurons exhibiting the noncholinergic mechanosensory depolarization, and in vitro capsaicin and SP desensitization reduced the amplitude of the depolarization. These results suggest that (1) both SP and AVP may be transmitters of noncholinergic potentials in the IMG, (2) some IMG neurons receive heterogeneous peptidergic innervation, and (3) noncholinergic transmission in the IMG is involved in sensory regulation of visceral autonomic function.

Thesis (M.D.) -- University of Adelaide, Dept. of Human Physiology and Pharmacology, 1970.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

Thesis (Ph.D.). / Written for the Dept. of Psychology. Title from title page of PDF (viewed 2008/03/12). Includes bibliographical references.

No description available.

Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: William B. Farquhar, Dept. of Health, Nutrition, & Exercise Sciences. Includes bibliographical references.

The gastrointestinal (GI) tract is subject to regulation by several neuronal networks, one of which is the sympathetic nervous system (SNS). Inflammatory bowel diseases (IBD), most importantly Crohn’s disease and ulcerative colitis, are chronic diseases of the GI tract that result in such functional symptoms as abdominal pain and diarrhea. These symptoms suggest an important role for dysregulation of the SNS in IBD, since this branch of the autonomic nervous system aids in regulation of blood flow, secretion and motility. Inflammatory cytokines that are elevated in the serum and tissue of IBD patients can have wide-ranging effects on neuronal function in vitro, and may be responsible for the functional alterations observed in vivo. With these neuronal alterations in mind, we hypothesized that interleukin-17, a novel cytokine with a central role in the pathogenesis of IBD, modulates the properties of sympathetic neurons innervating the gastrointestinal tract. Using electrophysiological techniques and Ca2+ imaging, we examined the effect of IL-17 on currents passing through voltage-gated Ca2+ channels in neurons from the superior mesenteric ganglion, which innervates the gut, and found that IL-17 inhibited these currents. In parallel, we found that IL-17 enhances the growth of sympathetic neurites in vitro. These effects depend upon activation of the nuclear factor κB (NF-κB) pathway, and do not appear to require glial cells. Therefore, dysregulated neural function during IBD may be due to direct effects of IL-17 on sympathetic neurons. / Thesis (Master, Physiology) -- Queen's University, 2009-09-03 11:33:53.63

Sympathetic catecholamines and co-transmitters released within the gastrointestinal (GI) tract provide dynamic regulation of gut motility, fluid secretion, blood flow and immune cell function. Pathological GI inflammation in patients with inflammatory bowel diseases (IBD) evokes functional and structural plasticity in sympathetic neurons that innervate the gut, which may contribute to symptom generation. The mechanisms responsible for aberrant sympathetic behaviour during colonic inflammation remain elusive, though evidence points to a role for mediators of the mucosal immune response. Interleukin (IL)-17 is the principal cytokine of the novel TH17 lineage of helper T cells. Based on mounting clinical, genetic and experimental evidence, IL-17 is thought to play a pivotal role in the immunopathogenesis of IBD. However, nothing is known of the contribution of IL-17 to sympathetic neuroplasticity during chronic inflammatory disease. We hypothesized that remodelling of postganglionic sympathetic axons occurs in response to exposure of axons to the inflamed colonic milieu and that IL-17 serves as the primary mediator of this neuroanatomical remodelling. An increase in tyrosine hydroxylase (TH) immunoreactivity, a marker of sympathetic axons, was observed in the muscularis externae and mucosae of colons from mice subjected to acute and chronic models of dextran sulphate sodium (DSS)-induced colitis. In parallel, we found markedly elevated levels of IL-17 in the serum and colonic tissues of mice with colitis. To investigate whether the colitis microenvironment promoted axonal growth, distal neurites of adult sympathetic neurons from the superior mesenteric ganglion (SMG) were incubated in supernatant collected from explant cultures of inflamed colon. Colitis supernatant enhanced neurite outgrowth from gut-projecting SMG neurons compared to supernatants from control colon. Importantly, this effect was abrogated following the addition of IL-17-neutralising antiserum to cultures. Moreover, IL-17 increased the morphological complexity of SMG neurites in vitro while none of the other inflammatory cytokines known to be elevated during IBD had a similar effect. These findings suggest a novel role for IL-17 as a mediator of sympathetic neuroanatomical plasticity during colonic inflammation. Whether this contributes to the functional deficits and chronic inflammatory response that occurs in the GI tract during IBD remains to be determined. / Thesis (Master, Physiology) -- Queen's University, 2011-08-10 09:40:13.514

Thesis (Ph. D.)--Michigan State University. Dept. of Neuroscience, 2008. / Title from PDF t.p. (viewed on July 23, 2009) Includes bibliographical references. Also issued in print.