Hemoglobin, the oxygen-carrying component of red blood cells, is known as a nitric oxide (NO) chelating agent. For this reason, hemoglobin has been used widely in studying the role of nitric oxide in long-term potentiation (LTP) and excitotoxicity. However, the direct electrophysiological actions of hemoglobin has not been examined. In this investigation, the actions of hemoglobin on rat hippocampal CAl neurons were studied since hemoglobin may be present in hemorrhagic stroke and other head injuries. Superfusion of rat hippocampal slices with 0.1 mM of bovine hemoglobin for 15 minutes was induced a significant depolarization associated with an increase in the input resistance. In addition, hemoglobin suppressed the evoked synaptic responses and increased the depolarization-induced discharge of action potentials, of rat hippocampal CAl neurons. These hemoglobin-mediated changes usually recovered partially 30 minutes after the removal of hemoglobin. While the depolarizing action of hemoglobin was enhanced in a calcium-free medium, it was not significantly changed by 2-amino-5-phosphonovalerate (APV) and 6- cyano-7-nitroquinoxaline-2,3-dione (CNQX). These observations suggest that the depolarizing action of hemoglobin is independent of the presence of extracellular calcium and activations of the excitatory amino acid receptors. Because hemoglobin has been observed to suppress the depolarizing action of glutamate, it is possible that hemoglobin suppresses the EPSP by interfering with the actions of glutamate. Although hemoglobin has been suggested to suppress LTP and excitability by scavenging nitric oxide (Garthwaite et al., 1988; Haley et al., 1992; 0’ Dell et al., 1991; Schuman and Madison, 1991), the reported actions of hemoglobin were not removed by pre-treatment with 100 pM or 500 pM of No-nitro-L-arginine, a nitric oxide synthase inhibitor. Similar to the scavenging property of hemoglobin, the iron content of hemoglobin probably did not contribute to the actions of hemoglobin since 0.4 mM or 2.0 mM of ferric chloride did not simulate the effects of hemoglobin. Because neurons can be exposed to hemoglobin in hemorrhagic stroke and head injuries, the electrophysiological actions of hemoglobin on rat hippocampal CAl neurons may be relevant to the neurological complications associated with intracranial hemorrhage and head injuries. Further studies on mechanisms of the electrophysiological actions of hemoglobin are necessary for understanding the role of hemoglobin in neuronal damages associated with hemorrhagic stroke and other head injuries.

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5-HT powerfully affects gastrointestinal function. However, the study of these effects is complicated because 5-HT from both mucosa and a subset of enteric neurons acts on multiple receptor subtypes in enteric tissues. The role of neural 5-HT has been difficult to isolate with current techniques. This thesis aimed to elucidate the role of 5-HT neurons in motility using anatomical and functional methods. In Chapter 2, confocal microscopy was used to examine over 95% of myenteric neurons in guinea pig jejunum, categorized neurochemically, to identify neurons that received anatomically-defined input from 5-HT interneurons. The data showed that cholinergic secretomotor neurons were strongly targeted by 5-HT interneurons. In another key finding, excitatory motor neurons were surrounded by 5-HT terminals; this could provide an anatomical substrate for the descending excitation reflex. Subgroups of ascending interneurons and neurons with immunoreactivity for NOS, were also targeted by 5-HT interneurons. Thus, subtypes of these neurons might act in separate reflex pathways. Despite strong physiological evidence for 5-HT inputs to AH/Dogiel type II neurons, few contacts were identified. In Chapter 3, the confocal microscopy survey was extended to the three other interneuron classes (VIP/NOS and SOM descending interneurons; calretinin ascending interneurons) of guinea pig small intestine. A high degree of convergence between the otherwise polarized ascending and descending interneuron pathways was identified.

Thesis (M.S.)--Oregon Graduate Center, 1988.

Thesis (Ph.D.)--Biomedical Engineering, Georgia Institute of Technology, 2007. / Committee Chair: Potter, Steve; Committee Member: Butera, Robert; Committee Member: DeWeerth, Stephen; Committee Member: Schumacher, Eric; Committee Member: Wenner, Pete.

Thesis (M.S.)--Georgia State University, 2009. / Title from title page (Digital Archive@GSU, viewed July 20, 2010) Andrey Shilnikov, Robert Clewley, Gennady Cymbalyuk, committee co-chairs; Igor Belykh, Vladimir Bondarenko, Mukesh Dhamala, Michael Stewart, committee members. Includes bibliographical references (p. 65-67).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 144-147).

Thesis (M. S.)--Psychology, Georgia Institute of Technology, 2007. / Schumacher, Eric, Committee Chair ; Corballis, Paul, Committee Member ; Jacko, Julie, Committee Member.

Part I abstract: Genetic methods for inducibly and reversibly inhibiting neuronal activity of specific neurons are critical for exploring the functions of neuronal circuits. The engineered human glycine receptor, called ivermectin (IVM)-gated silencing receptor (IVMR), has been shown to possess this ability in vitro, which abolish the binding with endogenous glycine and improve the sensitivity to ivermectin. Based on that, we constructed the knock-in plasmid which put IVMR in the downstream of a loxP-flanked STOP cassette. The Rosa26-IVMR mouse line was generated by inserting the plasmid into the Rosa26 locus though homologous recombination. IVMR expression can be induced by crossing with specific Cre mouse line or stereotactic injection of Cre-expressing virus. When expressing IVMR in unilateral striatal by injecting Cre-expressing virus, APO-induced rotation behavior was observed after inactivation of unilateral striatal neurons by administering ivermectin. Furthermore, 10mg/kg and 5mg/kg IVM are the effective ligand concentrations as they are able to induce obvious rotational behavior, but the effect last longer for 10mg/kg IVM than that for 5mg/kg. The physiological recording in vivo exhibited that neuron firing dramatically decreased in IVM-treated freely moving Rosa26-IVMR; Emx1-Cre mice and neuronal excitability in brain slice showed a substantial reduction as shown by increased threshold of the current needed to evoke the action potential and the reduced frequency of the action potential. In conclusion, our mouse line can inactivate the neuronal activity effectively in an inducible and reversible way with systemic administration of the ligand. So it provides a powerful tool for exploring selective circuit functions in freely behaving mice. Part II abstract: Schizophrenia is a chronic and severe mental disease which affects around 0.5%-1% population. However, the underlying cause are complex and remain unclear. Genetic abnormalities are considered to be the main risky factor. Although the typical symptoms start to occur between 18 and 30 age, the disturbance of neurodevelopmental process at earlier age is believed to be involved. To date, only a few of susceptibility genes are confirmed in human patients. Previously, through a meta-analysis of copy number variants (CNV) data from the International Schizophrenia Consortium and in vitro studies, we found a novel serine/threonine kinase gene, unc-51-like kinase 4 (Ulk4), as a risk factor for major mental disorders including schizophrenia. To investigate the Ulk4's roles in corticogenesis, Ulk4 knockout mice was employed. Though analyzing a series of developmental process during corticogenesis including laminar specification, neuronal migration in Ulk4 deficient mice, we found that Ulk4 loss led to the thinner layer II-IV, delayed neuronal migration and increased cell death in layer II-IV but did not affect the proliferation of progenitors which later give rise to the projection neurons in layer II-IV. Meantime the influence of Ulk4 deficiency on the deep layer (layer V and layer VI) development was limited. In conclusion, Ulk4 plays a crucial role on corticogenesis and regulates a variety of neurodevelopmental processes. When defective, this will lead to the increased risk of neurodevelopment disorders and also might be involved in the onset of mental disease including schizophrenia at early adolescence.

Hemoglobin, the oxygen-carrying component of red blood cells, is known as a nitric oxide (NO) chelating agent. For this reason, hemoglobin has been used widely in studying the role of nitric oxide in long-term potentiation (LTP) and excitotoxicity. However, the direct electrophysiological actions of hemoglobin has not been examined. In this investigation, the actions of hemoglobin on rat hippocampal CAl neurons were studied since hemoglobin may be present in hemorrhagic stroke and other head injuries. Superfusion of rat hippocampal slices with 0.1 mM of bovine hemoglobin for 15 minutes was induced a significant depolarization associated with an increase in the input resistance. In addition, hemoglobin suppressed the evoked synaptic responses and increased the depolarization-induced discharge of action potentials, of rat hippocampal CAl neurons. These hemoglobin-mediated changes usually recovered partially 30 minutes after the removal of hemoglobin. While the depolarizing action of hemoglobin was enhanced in a calcium-free medium, it was not significantly changed by 2-amino-5-phosphonovalerate (APV) and 6- cyano-7-nitroquinoxaline-2,3-dione (CNQX). These observations suggest that the depolarizing action of hemoglobin is independent of the presence of extracellular calcium and activations of the excitatory amino acid receptors. Because hemoglobin has been observed to suppress the depolarizing action of glutamate, it is possible that hemoglobin suppresses the EPSP by interfering with the actions of glutamate. Although hemoglobin has been suggested to suppress LTP and excitability by scavenging nitric oxide (Garthwaite et al., 1988; Haley et al., 1992; 0’ Dell et al., 1991; Schuman and Madison, 1991), the reported actions of hemoglobin were not removed by pre-treatment with 100 pM or 500 pM of No-nitro-L-arginine, a nitric oxide synthase inhibitor. Similar to the scavenging property of hemoglobin, the iron content of hemoglobin probably did not contribute to the actions of hemoglobin since 0.4 mM or 2.0 mM of ferric chloride did not simulate the effects of hemoglobin. Because neurons can be exposed to hemoglobin in hemorrhagic stroke and head injuries, the electrophysiological actions of hemoglobin on rat hippocampal CAl neurons may be relevant to the neurological complications associated with intracranial hemorrhage and head injuries. Further studies on mechanisms of the electrophysiological actions of hemoglobin are necessary for understanding the role of hemoglobin in neuronal damages associated with hemorrhagic stroke and other head injuries. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate