The effects of ammonia in pathophysiological concentrations were studied on the electrophysiology of putative glutamatergic synapses in the rat hippocampal formation; experiments were done in vitro and in vivo. Exposure of hippocampal slices to 5 mM ammonium chloride reduced the orthodromic population spike evoked in CA1 and CA3 pyramidal cell layer and in granule cell layer, following stimulation of their respective main afferent system. However, antidromic responses evoked in these groups of neurons were not affected by ammonia. In vitro, measures of the spike integral gave a better estimate of the extent of neuronal firing than did measures of the amplitude of the spikes. In vivo, perfusing the ventricular space with higher concentrations of ammonium salts (10 to 30 mM) produced similar effects to those shown in vitro on synaptic and non-synaptic responses in CA1 and CA3 regions. The sensitivity of pyramidal neurons to iontophoretic application of glutamate, aspartate and gamma-aminobutyric acid was not changed by ammonia. Experiments that used a paired pulse test showed an early effect of ammonia to cause disinhibition; this was attributed to a depression of the excitatory synapses on the inhibitory interneurons. It is concluded that hyperammonemia interferes with the release of glutamate, probably because ammonia inhibits glutaminase activity. The results suggest a deficiency of excitatory transmission as a possible mechanism in the development of the encephalopathy due to ammonia intoxication and the encephalopathies associated with hyperammonemia, e.g. hepatic encephalopathy.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.76734 |
| Date | January 1983 |
| Creators | Théôret, Yves. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000217448, proquestno: AAINK66587, Theses scanned by UMI/ProQuest. |
Page generated in 0.0026 seconds