Bakkar, Wafae2013-11-072013-11-0720082008Source: Masters Abstracts International, Volume: 48-01, page: 0303.http://hdl.handle.net/10393/27955http://dx.doi.org/10.20381/ruor-12329Glycine plays two roles in neurotransmission. It acts as the main inhibitory neurotransmitter in the spinal cord and brainstem and is a co-agonist of the N-methyl-D-aspartate receptor (NMDAR) throughout the central nervous system. Changes in extracellular levels of glycine modulate NMDAR functions and consequently, are critical for excitatory synaptic transmission. In the hippocampus, the extracellular levels of glycine at excitatory synapses are regulated by the presence of glycine transporters (type 1; GlyT1) located both on glia surrounding the synaptic cleft and on presynaptic terminals. Although the mechanism of glycine reuptake is well established, the mechanism of glycine release is still unknown. Here, we used immunocytochemical, confocal and electrophysiological techniques to determine the mechanism underlying glycine release in the stratum radiatum of the CA1 region of mouse hippocampus. Quantitative analysis of triple immunolabelings combining astrocytic, neuronal, glycinergic and glutamatergic markers showed that glycine was preferentially accumulated in glutamatergic presynaptic terminals. In addition, we found that the vast majority of the glutamatergic presynaptic terminals contained glycine and faced postsynaptic NMDARs. Moreover, using electrophysiological recordings we found that glycine released following electrical stimulation activated few glycine receptors on the postsynaptic neurons but instead, strongly modulated the amplitude of NMDAR currents. Overall, our data indicate that glycine is released from glutamatergic presynaptic terminals upon neuronal activity to modulate NMDAR function.67 p.enBiology, Neuroscience.Thesis