Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling


Whereas glutamate transporters in glial cells and postsynaptic neurons contribute significantly to re-uptake of synaptically released transmitter, the functional role of presynaptic glutamate transporters is poorly understood. Here, we used electrophysiological recording to examine the functional properties of a presynaptic glutamate transporter in rat retinal rod bipolar cells and its role in regulating glutamatergic synaptic transmission between rod bipolar cells and amacrine cells. Release of glutamate activated the presynaptic transporter with a time course that suggested a perisynaptic localization. The transporter was also activated by spillover of glutamate from neighboring rod bipolar cells. By recording from pairs of rod bipolar cells and AII amacrine cells, we demonstrate that activation of the transporter-associated anion current hyperpolarizes the presynaptic terminal and thereby inhibits synaptic transmission by suppressing transmitter release. Given the evidence for presynaptic glutamate transporters, similar mechanisms could be of general importance for transmission in the nervous system.

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Figure 1: Localization of a glutamate transporter at axon terminal of rod bipolar cells.
Figure 2: Kinetics and concentration-response relationship of glutamate transporter at rod bipolar axon terminals.
Figure 3: Synaptic release of glutamate activates the transporter in rod bipolar cells.
Figure 4: Spontaneous glutamate release activates the transporter in rod bipolar cells.
Figure 5: Spillover of glutamate between rod bipolar cells activates the transporter.
Figure 6: Action and interaction of excitatory and inhibitory conductances at rod bipolar cell axon terminals.
Figure 7: Activation of glutamate transporter in rod bipolar cell axon terminals suppresses synaptic transmission.


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Financial support from the Norwegian Research Council (NFR 155397/310 and 161217/V40), the Meltzer fund (University of Bergen) and the Faculty of Medicine at the University of Bergen (fellowships for M.L.V. and S.H.M.) is gratefully acknowledged.

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Correspondence to Espen Hartveit.

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Veruki, M., Mørkve, S. & Hartveit, E. Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling. Nat Neurosci 9, 1388–1396 (2006).

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