Localization and functional characterization of the nitric oxide and carbon monoxide signaling pathways in the postnatal rat hippocampal formation
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Abstract
In the rat hippocampus, nitric oxide (NO) and carbon monoxide (CO) both function as signaling molecules involved in long-term plasticity. In neurons, NO generated by the enzyme neuronal nitric oxide synthase (nNOS) and CO generated by hemeoxygenase-2 (HO-2), can activate soluble guanylyl cyclase (sGC) to produce cyclicguanosine-monophosphate (cGMP). There has not been a complete functional localization of these signaling pathways in the sub-regions and laminae of the hippocampal formation. In this work, transverse slices of ventral hippocampus (200-250 um thick) from P17-P21 Long Evans rats were used to characterize and localize the NO and CO signaling pathways in the hippocampus. Immunohistochemistry was used to characterize and localize cells containing nNOS, H0-2 and cGMP. Additionally, the NO sensitive fluorescent dye, DAF-FM, was used to localize the production of NO in response to stimulation with NMDA or AMPA. nNOS was immunolocalized in twenty-four distinct neuron types, in varicose and smooth processes, and in axons of the alveus fiber pathway. H0-2 was found in all granule cells, hilar cells and pyramidal cells. Sparse principal cells had both nNOS and H0-2, and sparse non-principal cells had H0-2 and cGMP, but no cells had both nNOS and cGMP. In response to stimulation with a NO-donor, cGMP was found in the following: dendrites and somata of three distinct basket cell types in the dentate gyrus; three distinct interneurons; axonal fibers in the perforant pathway and alveus; and in astrocytes in CA1. Simultaneous stimulation with both NO and CO produced a region specific synergistic increase in cGMP production. NMDA or AMPA stimulated cGMP was localized in the following: varicose processes in the neuropil; in varicose processes surroundingĀ· pyramidal cells in CAl and CA3; in astrocytes in CAl; and in smooth long range processes in CA1 and the alveus. In response to stimulation with NMDA or AMPA NO-induced fluorescence was found in the principal cell layer, alveus, apical dendrites of pyramidal cells in CA1, and in occasional granule-cell somata. The results presented here indicate that NO-cGMP functions in a wide variety of hippocampal synaptic circuits and that CO interacts with NO in the modulation of cGMP levels.
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Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.