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Visual stimuli–induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors

Abstract

Local GABA (γ-aminobutyric acid) circuits contribute to sensory experience–dependent refinement of neuronal connections in the developing nervous system, but whether GABAergic synapses themselves can be rapidly modified by sensory stimuli is largely unknown. Here we report that repetitive light stimuli or theta burst stimulation (TBS) of the optic nerve in the developing Xenopus retinotectal system induces long-term potentiation (LTP) of glutamatergic inputs but long-term depression (LTD) of GABAergic inputs to the same tectal neuron. The LTD is due to a reduction in presynaptic GABA release and requires activation of presynaptic NMDA (N-methyl-D-aspartate) receptors (NMDARs) and coincident high-level GABAergic activity. Thus, the presynaptic NMDAR may function as a coincidence detector for adjacent glutamatergic and GABAergic activities, leading to coordinated synaptic modification by sensory experience.

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Figure 1: Visual stimuli induce potentiation of glutamatergic inputs.
Figure 2: Visual stimuli induce depression of GABAergic inputs.
Figure 3: Converging glutamatergic and GABAergic inputs on single tectal neurons.
Figure 4: LTP of excitatory synapses requires postsynaptic spiking and an increase in Ca2+.
Figure 5: LTD of inhibitory synapses depends on presynaptic NMDAR activation.
Figure 6: Blocking postsynaptic NMDARs cannot prevent NMDAR-dependent GABAergic LTD.
Figure 7: Presynaptic expression of GABAergic LTD.
Figure 8: Presynaptic modulation of GABAergic transmission.

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Acknowledgements

This work was supported by a grant from the US National Institutes of Health (EY014949) and a Wellcome Trust Fellowship (to M.V.C).

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Correspondence to Mu-ming Poo.

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Supplementary information

Supplementary Fig. 1

Simulated NMDAR-mediated currents associated with bursting spikes and subthreshold responses. (PDF 1014 kb)

Supplementary Fig. 2

Synaptic delay, decay time, and rise time of EPSCs and IPSCs. (PDF 27 kb)

Supplementary Fig. 3

Coincident NMDAR activation and presynaptic activity are required for GABAergic LTD. (PDF 23 kb)

Supplementary Methods (PDF 7 kb)

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Lien, CC., Mu, Y., Vargas-Caballero, M. et al. Visual stimuli–induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors. Nat Neurosci 9, 372–380 (2006). https://doi.org/10.1038/nn1649

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