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Previous Article | Next Article
The Journal of Neuroscience, March 15, 2003, 23(6):2040
Neuronal Glutamate Uptake Contributes to GABA Synthesis and Inhibitory Synaptic Strength
Gregory C. Mathews1, 2 and Jeffrey S. Diamond1 1 Synaptic Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4066, and 2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287
Neurons must maintain a supply of neurotransmitter in their presynaptic terminals to fill synaptic vesicles. GABA is taken up into inhibitory terminals by transporters or is synthesized from glutamate by glutamic acid decarboxylase. Here we report that glutamate transporters supply GABAergic terminals in the hippocampus with glutamate, which is then used to synthesize GABA for filling synaptic vesicles. Glutamate transporter antagonists reduced IPSC and miniature IPSC (mIPSC) amplitudes, consistent with a reduction in the amount of GABA packaged into each synaptic vesicle. This reduction occurred rapidly and independently of synaptic activity, suggesting that modulation of vesicular GABA content does not require vesicle release and refilling. Raising extracellular glutamate levels increased mIPSC amplitudes by enhancing glutamate uptake and, consequently, GABA synthesis. These results indicate that neuronal glutamate transporters strengthen inhibitory synapses in response to extracellular glutamate. This modulation appears to occur under normal conditions and may constitute a negative feedback mechanism to combat hyperexcitability.
Key words: glutamate transporters; synaptic vesicles; GABA; metabolism; inhibition; hippocampus
Copyright © 2003 Society for Neuroscience 0270-6474/03/2362040-09$05.00/0
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