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Disruption of glutamate metabolism reveals that presynaptic glutamate concentration directly regulates postsynaptic glutamate receptor levels



Disruption of glutamate metabolism reveals that presynaptic glutamate concentration directly regulates postsynaptic glutamate receptor levels



Society for Neuroscience Abstracts 26(1-2): Abstract No. 784-11



Glutamate decarboxylase (GAD), which converts glutamate into GABA, is abundant at the glutamatergic (non GABAergic) Drosophila NMJ. Genetic elimination of GAD function in Drosophila results in paralysis and embryonic lethality. Electrophysiological and immunohistochemical analysis reveals a dramatic decrease (to approximately 15% WT levels) in the number of postsynaptic glutamate receptors, but otherwise morphologically normal synapses. Overexpression of GAD in a subset of motor neurons results in a selective and dramatic increase (500% WT) in levels of postsynaptic glutamate receptors. Thus, postsynaptic glutamate receptor number is strongly correlated with presynaptic GAD function. Since the Drosophila NMJ is not GABAergic, we conclude that GAD works developmentally to limit glutamate, which acts as a negative regulator of postsynaptic glutamate receptors. Postsynaptic glutamate receptor synthesis and clustering requires contact by the presynaptic motor neuron, and severe alterations in presynaptic electrical activity disrupt postsynaptic receptor levels. However, receptor levels are not significantly affected by mutations that disrupt vesicular exocytosis. We believe that once induced by motor neuron contact, postsynaptic glutamate receptor levels are developmentally controlled by extracellular glutamate concentration. Extracellular glutamate is released predominantly by nonvesicular mechanisms, with transient fluctuations and minor alterations due to synaptic activity.

Accession: 034749299

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