Study Of Hippocampal Glycine Receptor Function

Glycine is a common amino acid and it exposes at least 5 kind of function in central nervous system. First, it can act on strychnine-sensitive glycine receptor (GlyR) chloride channels in mature animal to induce neuronal inhibition. Second, in a relative low concentration, it can act as co-agonist of NMDA receptors (NMDAR) to increase NMDAR-mediated responses. But in high concentration, glycine can prime NMDAR internalization. Glycine can directly activate a kind of NMDAR, NR3-NMDAR, to induce excitatory response. Furthermore, cross-talk of glycine and another inhibitory neurotransmitter GABA exist between their receptors.Functional glycine receptors are enriched in the hippocampus, but no glycinergic neurotransmission has been found in this region and the roles of GlyRs in hippocampal function are unclear. It has been reported that GlyRs in the hippocampus may be tonically activated and suppress hyperexcitability. Considered the facts that the role of glycine is regulated by its uptake and powerful glycine transporters (GlyT) exist in the hippocampus, the transporter might be an important contributor to the role of GlyRs in the hippocampus. Through uptake and reverse transport, GlyTs can take part in regulation of glycine concentration so that the function of excitatory and inhibitory neurotransmission. In this study, we used field potential and whole-cell recording in the hippocampal slices, with bath drug application or blockage of glycine transporter to activate GlyRs, to study the role of GlyRs in synaptic transmission, information processing and homeostasis.In the first study, we examined the effect of GlyR activation on paired-pulse stimulation of the whole-cell postsynaptic currents (PSCs) in the Schaffer-CA1 synapses in rat hippocampal slices. Bath application of glycine reduced the amplitude of PSCs, accompanying by an increase in holding current and resting conductance. Moreover, glycine application increased the paired-pulse ratio (PPR)...