Elements of glutamate release, action and reuptake
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AbstractNeurons conduct electrical signals, and signals pass from one neuron to the next by the use of chemical substances in specialized contacts, synapses. In most synapses, the transmitter is the amino acid glutamate.
A machinery of proteins conducts the task of glutamate release, binding/effect (action) and reuptake, at speeds of up to hundreds of times every second. The bits of this machinery are not at all fully understood and differ between areas of the brain. It is the principal aim of this thesis to discuss the role of some of the proteins that are involved and considered essential. The findings can be summarized as follows:
First, signal transmission was shown to be enhanced in mossy fibre terminals of the hippocampus when stimulated at a specific range of frequencies, by a mechanism dependent on the proteins synapsin I+II and actin. This was shown by a loss of function and change in morphology in mice genetically altered to lack synapsin I+II. Also, the localization of synapsin III was described at high resolution.
Secondly, in the mice described above, signal receiving neurons were found to have increased sensitivity. This was described as a change in composition of receptor proteins (GluR1 and GluR2/3) which glutamate acts upon. The precise location was determined using quantitative immunolabeling electron microscopy. It is suggested that this change can contribute to epileptic seizures seen in the genetically altered mice.
Signals are terminated by the removal of glutamate from the extracellular space. Last, a protein (GLAST) that transports glutamate away from the synapse into surrounding cells (glia) was characterized. Specifically, by the use of electrophysiological patch clamping techniques, the number and identity of ions involved in and driving its transporter cycle was determined.
List of papers.
Paper I: Gylterud Owe S, Bogen IL, Walaas SI, Storm-Mathisen J, & Bergersen LH (2005). Ultrastructural quantification of glutamate receptors at excitatory synapses in hippocampus of synapsin I+II double knock-out mice. Neuroscience 136, 769-777.
Paper II: Owe SG, Marcaggi P, & Attwell D (2006). The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal glia. J Physiol 577, 591-599
Paper III: Owe SG, Jensen V, Evergren E, Ruiz A, Shupliakov O, Kullmann DM, Storm-Mathisen J, Walaas SI, Hvalby O, & Bergersen LH (2008). Synapsin- and Actin-Dependent Frequency Enhancement in Mouse Hippocampal Mossy Fiber Synapses. Cereb Cortex [Epub ahead of print].