Editors' ChoiceNeurobiology

EeeGAD! Glutamatergic Synapse Regulation

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Science's STKE  01 Aug 2000:
Vol. 2000, Issue 43, pp. tw4
DOI: 10.1126/stke.2000.43.tw4

The Drosophila neuromuscular junction (NMJ) is a glutamatergic synapse. Featherstone et al. identified glutamic acid decarboxylase (Dgad1) in a screen of mutants that are embryonic lethal with normal morphology, but that exhibited movement defects and aberrant neuromuscular synapses (detected by electrophysiological techniques). Biochemical analysis of GAD confirms that the enzyme can convert glutamate to GABA and that the mutant alleles lack enzymatic activity; however, GABA and GABA receptors are not detected at the Drosophila NMJ, suggesting that GAD is not involved in the synthesis of GABA at these synapses. GAD was detected in the presynaptic neuron of the NMJ by immunostaining. The electrophysiological defects observed in the mutants are consistent with normal clustering of glutamate receptors with normal single-channel activity, but greatly reduced channel density, suggesting that glutamate metabolism is a key regulator of postsynaptic receptor density. Furthermore, overexpression of GAD led to increased receptor activity. The authors suggest that the mechanism for GAD regulation of postsynaptic density is due to decreased glutamate metabolism, which increases intracellular glutamate concentrations leading to a decreased gradient for the glutamate transporter and, thus, increased synaptic glutamate concentrations due to nonvesicular glutamate release and concomitant down-regulation of postsynaptic receptors.

Featherstone, D.E., Rushton, E.M., Hilderbrand-Chae, M., Phillips, A.M., Jackson, F.R., and Broadie, K. (2000) Presynaptic glutamic acid decarboxylase is required for induction of the postsynaptic receptor field at a glutamtergic synapse. Neuron 27: 71-84. [Online Journal]