An electrophysiological investigation of monosialoganglioside in the mammalian central nervous system

This thesis focuses on the functional role of monosialoganglioside (GM1) in neuronal activity and synaptic transmission of rat hippocampal slices. The slices were placed in an interface recording chamber and constantly superfused with oxygenated saline at 33$ sp circ$. Both extracellular and intracellular (current- and voltage-clamp) recording techniques were used to measure the field potentials and postsynaptic responses respectively. Our findings indicated that GM1 induces a small inward current in CA1 pyramidal neurons, depresses their high voltage activated (HVA) Ca$ sp{2+}$ currents, and selectively facilitates the excitatory synaptic inputs while reducing the inhibitory ones.The most probable mechanism underlying the selective enhancement of excitatory inputs by GM1 is an increase in glutamate release, since the amplitudes and frequency of spontaneous miniature postsynaptic responses, recorded either in the presence or absence of presynaptic cell firing, were cosistently increased. When L-glutamate was applied iontophoretically in the dendritic region, GM1 transiently potentiated the postsynaptic glutamate currents, thus further indicating a GM1-induced enhancement of glutamatergic transmission. In contrast, both spontaneous and evoked inhibitory postsynaptic responses were suppressed by GM1. This effect is dependent on changes in excitatory inputs to inhibitory interneurons because in the presence of tetrodotoxin and/or kynurenic acid, GM1 did not alter the amplitude of the monosynaptic IPSPs or the frequency of spontaneous miniature IPSCs.Both the GM1-induced inward current and the reduction of postsynaptic HVA Ca$ sp{2+}$ currents were antagonised by kynurenic acid, suggesting that these effects might be caused by glutamate receptor activation. By raising intraneuronal Ca$ sp{2+}$ concentration, the potentiated glutamate release would trigger Ca$ sp{2+}$-dependent Ca$ sp{2+}$ inactivation, and thus explain the reduction in HVA Ca$ sp{2+}$ currents.In conclusion, most of the GM1 actions observed in this project can be explained on the basis of a GM1-induced facilitation of excitatory transmission, mediated especially via enhanced glutamate release