This thesis focuses on the effects of adenosine release on neuronal activity in the CA1 region of rat hippocampal slices, especially during energy deprivation, and related events. The overall aim was to find out how brain function is suppressed when metabolism is greatly reduced by the lack of oxygen or glucose, or by cyanide applications, and therefore to provide some insights in the cellular mechanisms underlying these depressant effects. Experiments were carried out on hippocampal slices kept submerged and constantly superfused with oxygenated saline at 33-34$ sp circ$C. Energy deprivation was produced by either removal of oxygen or glucose, or applying cyanide. Extra-/intracellular and whole-cell patch recordings (both in current- and voltage-clamp mode) were used to assess synaptic function and postsynaptic properties. / A most interesting phenomenon is the reversible suppression of neuronal function that occurs in the very early phase of energy deprivation. Adenosine receptor antagonists reversibly reduce this suppression. In contrast, neither glibenclamide, a blocker of ATP-sensitive K$ sp+$ channels, nor a nitric oxide synthase inhibitor prevents the suppression of neuronal activity induced by energy deprivation. The depressant effect acts selectively on excitatory synapses, since in the presence of excitatory receptor antagonists, anoxia causes only a small reduction of monosynaptic inhibitory responses. Also adenosine antagonists, but not the K$ rm sb{ATP}$ channel blocker, reversibly attenuate anoxia- and cyanide-induced post-synaptic hyperpolarizations. / Furthermore, under normoxic conditions, ongoing adenosine release exerts an inhibitory tone on excitatory synapses but not on inhibitory synapses. The effects of ongoing adenosine release are mainly on synapses, since after blockade of transmitter actions, ongoing adenosine release has no detectable effect on membrane conductance. / The evidence presented in this thesis shows that increased adenosine release induced by energy deprivation is a major cause of the reversible loss of synaptic transmission and fall in membrane resistance, and therefore indicates a mechanism by which adenosine release contributes to the reversal depression of neuronal activity seen during energy deprivation.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.40305 |
| Date | January 1996 |
| Creators | Zhu, Ping jun |
| Contributors | Krnjevic, K. (advisor) |
| 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 Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001496033, proquestno: NN12524, Theses scanned by UMI/ProQuest. |
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